Note: Descriptions are shown in the official language in which they were submitted.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
1
TITLE
FUNGICIDAL HALOMETHYL KETONES AND HYDRATES
AND THEIR MIXTURES
FIELD OF THE INVENTION
This invention relates to certain halomethyl ketone and hydrate derivatives,
their N-oxides
and salts, and to mixtures and compositions comprising such halomethyl ketone
and hydrate
derivatives and methods for using such derivatives and their mixtures and
compositions as
fungicides.
BACKGROUND OF THE INVENTION
The control of plant diseases caused by fungal plant pathogens is extremely
important in
achieving high crop efficiency. Plant disease damage to ornamental, vegetable,
field, cereal and
fruit crops can cause significant reduction in productivity and thereby result
in increased costs to
the consumer. In addition to often being highly destructive, plant diseases
can be difficult to
control and may develop resistance to commercial fungicides. Many products are
commercially
available for these purposes, but the need continues for new fungicidal
compounds which are
more effective, less costly, less toxic, environmentally safer or have
different sites of action.
Besides introduction of new fungicides, combinations of fungicides are often
used to facilitate
disease control, to broaden spectrum of control and to retard resistance
development.
Furthermore, certain rare combinations of fungicides demonstrate a greater-
than-additive (i.e.
synergistic) effect to provide commercially important levels of plant disease
control. The
advantages of particular fungicide combinations are recognized in the art to
vary, depending on
such factors as the particular plant species and plant disease to be treated,
and whether the plants
are treated before or after infection with the fungal plant pathogen.
Accordingly new
advantageous combinations are needed to provide a variety of options to best
satisfy particular
plant disease control needs. Such combinations have now been discovered.
SUMMARY OF THE INVENTION
This invention relates to a fungicidal composition (i.e. combination, mixture)
comprising
(a) at least one compound selected from the compounds of Formula 1 (including
all
stereoisomers), tautomers, N-oxides, and salts thereof,
E., L ......--J===õ. ..õ..-T
1
wherein
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
2
T is selected from the group consisting of:
R2c
R....2aR2bX
Xxy
).LR1 and i%R1
R2d
T-1 T-2 T-3
wherein the bond extending to the left is attached to A;
R1 is CF3, CHF2, CC13, CHC12, CF2C1, CFC12 or CHFC1;
W is 0, S or NR3;
R3 is H, cyano, nitro, C(=0)0H, benzyl, C1-C4 alkyl, C2-C4 alkylcarbonyl, C2-
C4
haloalkylcarbonyl, 0R3a or NR3bR3c;
R3a is H, benzyl, C1-C4 alkyl, C2-C4 alkylcarbonyl or C2-C4 haloalkylcarbonyl;
R3b is H, C1-C4 alkyl, C2-C4 alkylcarbonyl or C2-C4 haloalkylcarbonyl;
R3C is H or C1-C4 alkyl; or
R3b and R3C are taken together to form a 4- to 6-membered fully saturated
heterocyclic
ring, each ring containing ring members, in addition to the connecting
nitrogen atom,
selected from carbon atoms and up to 2 heteroatoms independently selected from
up
to 2 0, up to 2 S and up to 2 N atoms, each ring optionally substituted with
up to 2
methyl groups;
X is 0, S or NR5a;
Y is 0,S or NR5b;
R5a and R5b are each independently H, hydroxy or C1-C4 alkyl;
R2a and R2b are each independently H, C1-C4 alkyl, C2-C4 alkenyl, C3-C15
trialkylsilyl,
C3-C15 halotrialkylsilyl, (CR4aR4b)p_0H, (CR4aR4b)p_SH, (CR4aR4b)p_Cl or
(CR4aR4b)p_Br; or
R2a and R2b are taken together with the atoms X and Y to which they are
attached to form
a 5- to 7-membered saturated ring containing ring members, in addition to the
atoms
X and Y, selected from carbon atoms, wherein up to 2 carbon atom ring members
are
independently selected from C(=0) and C(=S), the ring optionally substituted
with
up to 2 substituents independently selected from halogen, cyano, C1-C2 alkyl,
C1-C2
haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy on carbon atom ring members;
R2c is C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4
alkynyl,
C2-C4 haloalkynyl or trifluoromethylsulfonyl, each optionally substituted with
up 2
substituents independently selected from cyano, hydroxy, SCI\T and C1-C2
alkoxy;
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
3
R2d is H, cyano, halogen or C1-C4 alkyl;
each R4a and R4b is independently H or C1-C4 alkyl;
p is 2 or 3;
when T is T-1 or T-2, then A is Ai_A2_cR6aR6b, wherein A1 is connected to J,
and
c R6aR6b is connected to T;
when T is T-3, then A is A1-A2, wherein A1 is connected to J, and A2 is
connected to T;
Al is cR6cR6d, N(-r-,lc7a,, ) 0 or S;
A2 is a direct bond, CR6eR6f, N(R7b), 0 or S;
R6a, R6b, R6c, R6d, R6e and R6f are each independently H, cyano, hydroxy,
halogen,
C(=0)0CH3 or C1-C4 alkyl;
R7a and R7b are each independently H, C(=0)H, cyano, C1-C4 alkyl or C2-C4
alkylcarbonyl;
J is selected from the group consisting of:
(R
8)q
)q 441 , (R _ ._.._ ,
)q ¨N
J-1 J-2 J-3 J-4
, ______________ N
(R
_ y / 1 N.1
, 8)q 40:1 , (R8)cni
(R8)q ¨N N
N
J-5 J-6 J-7 J-8
I I
YN
N) ."--- 1
( %.
, (R8)q¨ 'i , . , .>< N.>< , N R8)q (R8)q
(R8)q
J-9 J-10 J-11 J-12
1.y ...../ S
and
N>sl\I
(R8)(\\- 4'
(R8)q
J-13 J-14
wherein the bond extending to the left is attached to L, and the bond
extending to the right
is attached to A;
each R8 is independently F, Cl, I, Br, cyano, methyl, trifluoromethyl or
methoxy;
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
4
q is 0, 1, 2, 3 or 4;
L is (CR9aR9b)n;
each R9a and R9b is independently H, halogen, cyano, hydroxy, nitro, C1-C3
alkyl, C1-C3
haloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy;
nis 0,1,2 or3;
E is C1-C6 alkyl or C1-C6 haloalkyl; or
E is El or E2;
El is amino, cyano, hydroxy, nitro, CH(=0), C(=0)0H, C(=0)NH2, C(=S)NH2,
OC(=0)NH2, OC(=S)NH2, NHC(=0)NH2, NHC(=S)NH2, SC1\1,
-CH=NNHC(=0)0C1-C6 alkyl or -N(OCH3)C(=0)C1-C6 alkyl; or
El is C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C1-C6 alkylthio, C2-C6
alkenylthio, C2-C6 alkynylthio, C1-C6 alkylsulfinyl, C2-C6 alkenylsulfinyl, C2-
C6
alkynylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 alkenylsulfonyl, C2-C6
alkynylsulfonyl,
C1-C6 alkylsulfonylamino, C2-C6 alkenylsulfonylamino, C2-C6
alkynylsulfonylamino, C1-C6 alkylaminosulfonyl, C2-C6 dialkylaminosulfonyl,
C2-C6 alkenylaminosulfonyl, C2-C6 alkynylaminosulfonyl, C1-C6
alkylaminosulfonylamino, C2-C6 alkenylaminosulfonylamino, C2-C6
alkynylaminosulfonylamino, C2-C6 alkylcarbonyl, C3-C6 alkenylcarbonyl, C3-C6
alkynylcarbonyl, C2-C6 alkylaminocarbonyl, C3-C6 alkenylaminocarbonyl, C3-C6
alkynylaminocarbonyl, C2-C6 alkylcarbonylamino, C3-C6 alkenylcarbonylamino,
C3-C6 alkynylcarbonylamino, C2-C6 alkylaminocarbonylamino, C3-C6
alkenylaminocarbonylamino, C3-C6 alkynylaminocarbonylamino, C2-C6
alkylcarbonyloxy, C3-C6 alkenylcarbonyloxy, C3-C6 alkynylcarbonyloxy, C2-C6
alkoxycarbonyl, C3-C6 alkenyloxycarbonyl, C3-C6 alkynyloxycarbonyl, C2-C6
alkylaminocarbonyloxy, C3-C6 alkenylaminocarbonyloxy, C3-C6
alkynylaminocarbonyloxy, C2-C6 alkoxycarbonylamino, C3-C6
alkenyloxycarbonylamino, C3-C6 alkynyloxycarbonylamino, C2-C6
alkylamino(thiocarbonyl)oxy, C3-C6 alkenylamino(thiocarbonyl)oxy, C3-C6
alkynylamino(thiocarbonyl)oxy, C2-C6 alkoxy(thiocarbonyl)amino, C3-C6
alkenyloxy(thiocarbonyl)amino, C3-C6 alkynyloxy(thiocarbonyl)amino, C2-C6
alkyl(thiocarbonyl), C2-C6 (alkylthio)carbonyl, C3-C6 alkenyl(thiocarbonyl),
C3-C6
(alkenylthio)carbonyl, C3-C6 alkynyl(thiocarbonyl), C3-C6
(alkynylthio)carbonyl,
C2-C6 alkylamino(thiocarbonyl), C3-C6 alkenylamino(thiocarbonyl), C3-C6
alkynylamino(thiocarbonyl), C2-C6 alkyl(thiocarbonyl)amino, C2-C6
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
(alkylthio)carbonylamino, C3-C6 alkenyl(thiocarbonyl)amino, C3-C6
(alkenylthio)carbonylamino, C3-C6 alkynyl(thiocarbonyl)amino, C3-C6
(alkynylthio)carbonylamino, C2-C6 alkylamino(thiocarbonyl)amino, C3-C6
alkenylamino(thiocarbonyl)amino or C3-C6 alkynylamino(thiocarbonyl)amino,
5 wherein each carbon atom is optionally substituted with up to 1
substituent selected
from R10a and up to 3 substituents independently selected from R10b;
R10a is phenyl optionally substituted with up to 3 substituents independently
selected from
Riia; or a 5- to 6-membered heterocyclic ring containing ring members selected
from
carbon atoms and 1 to 4 heteroatoms independently selected from up to 2 0, up
to 2
S and up to 4 N atoms, wherein up to 3 carbon atom ring members are
independently
selected from C(=0) and C(=S), and sulfur atom ring members are independently
S(=0)u(=NR12)v, each ring optionally substituted with up to 3 substituents
independently selected from R11a on carbon atom ring members and 1211b on
nitrogen atom ring members;
each 1210b is independently amino, cyano, halogen, hydroxy, nitro, SCI\T, -SH,
C1-C4
alkyl, C1-C4 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C4 alkoxy,
C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl,
C1-C4
haloalkylsulfonyl, C1-C4 alkylamino, C2-C4 dialkylamino, C2-C4 alkylcarbonyl,
C2-C4 haloalkylcarbonyl, C2-05 alkoxycarbonyl, C2-05 haloalkoxycarbonyl, C2-05
alkylaminocarbonyl or C3-05 dialkylaminocarbonyl;
each R11' is independently halogen, hydroxy, cyano, amino, nitro, C1-C4 alkyl,
C1-C4
haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 hydroxyalkyl, C3-C6 cycloalkyl,
C4-C7 cycloalkylalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkenyloxy, C2-C4
alkynyloxy, C2-C4 alkoxyalkyl, C2-C6 alkylcarbonyloxy, C1-C4 alkylthio, C1-C4
haloalkylthio, C2-C6 alkylcarbonylthio, C1-C4 alkylsulfinyl, C1-C4
haloalkylsulfinyl,
C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfonyloxy, C1-C4
alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkylcarbonyl,
C3-05 alkenylcarbonyl, C3-05 alkynylcarbonyl, C4-C7 cycloalkylcarbonyl, C5-C8
cycloalkylalkylcarbonyl, C2-C6 alkoxycarbonyl, C3-C7 alkenyloxycarbonyl, C3-C7
alkynyloxycarbonyl, C4-C7 cycloalkoxylcarbonyl, C5-C8
cycloalkylalkoxylcarbonyl,
C2-C6 alkylaminocarbonyl, C3-C6 alkenylaminocarbonyl, C3-C6
alkynylaminocarbonyl, C4-C7 cycloalkylaminocarbonyl, C5-C8
cycloalkylalkylaminocarbonyl, C3-C8 dialkylaminocarbonyl or C3-C6
trialkylsilyl;
each Rub is independently C(=0)H, C1-C3 alkyl, C1-C3 alkoxy, C2-C3
alkylcarbonyl or
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
6
C2-C3 alkoxycarbonyl;
each R12 is independently H, cyano, C1-C3 alkyl or C1-C3 haloalkyl;
each u and v are independently 0, 1 or 2, provided that the sum of u and v are
0, 1 or 2;
E2 is G-Z, wherein Z is attached to L;
G is phenyl optionally substituted with up to 3 substituents independently
selected from
R13; or
G is a 5- to 6-membered heteroaromatic ring, each ring containing ring members
selected
from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2
0, up
to 2 S and up to 4 N atoms, each ring optionally substituted with up to 3
substituents
independently selected from R13; or
G is a 3- to 7-membered nonaromatic ring or an 8- to 11-membered bicyclic ring
system,
each ring or ring system containing ring members selected from carbon atoms
and
optionally up to 4 heteroatoms independently selected from up to 2 0, up to 2
S and
up to 4 N atoms, wherein up to 2 ring members are independently selected from
C(=0), C(=S), S(=0) and S(=0)2, each ring or ring system optionally
substituted
with up to 3 substituents independently selected from R13;
each R13 is independently cyano, halogen, hydroxy, nitro, -SH, SF5, CH(=0),
C(=0)0H,
NR14aRl4b, C(=0)NR14aRl4b, C(=0)C(=0)NR14aRl4b, C(=S)NR14aRl4b,
C(R15)=NR16, N=CR17NR18aRl8b or _u_v_Q; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6
alkynyl, C3-C7 cycloalkyl, C3-C7 cycloalkenyl, C1-C6 alkoxy, C2-C6 alkenyloxy,
C2-C6 alkynyloxy, C3-C7 cycloalkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-
C6
alkylsulfonyl, C1-C6 alkylaminosulfinyl, C2-C6 dialkylaminosulfinyl, C1-C6
alkylsulfonyloxy, C1-C6 alkylsulfonylamino, C2-C6 alkylcarbonyl, C4-C7
cycloalkylcarbonyl, C2-C6 alkoxycarbonyl, C3-C6 alkenyloxycarbonyl, C3-C6
alkynyloxycarbonyl, C4-C7 cycloalkoxycarbonyl, C3-C6 alkoxycarbonylcarbonyl,
C2-C6 alkylcarbonyloxy, C4-C7 cycloalkylcarbonyloxy, C2-C6 alkoxycarbonyloxy,
C4-C7 cycloalkoxycarbonyloxy, C2-C6 alkylaminocarbonyloxy, C4-C7
cycloalkylaminocarbonyloxy, C2-C6 alkylcarbonylamino, C4-C7
cycloalkylcarbonylamino, C2-C6 alkoxycarbonylamino, C4-C7
cycloalkoxycarbonylamino, C2-C6 alkylaminocarbonylamino, C4-C7
cycloalkylaminocarbonylamino or C2-C6 dialkoxyphosphinyl, each optionally
substituted with up to 3 substituents independently selected from R19;
each R14a is independently H, cyano, hydroxy, C1-C4 alkyl, C1-C4 haloalkyl, C2-
C4
alkenyl, C2-C4 haloalkenyl, C2-C4 alkynyl, C2-C4 haloalkynyl, C1-05 alkoxy, C2-
C4
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
7
alkoxyalkyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C2-C4
alkylthioalkyl,
C2-C4 alkylsulfinylalkyl, C2-C4 alkylsulfonylalkyl, C2-C4 alkylcarbonyl, C2-C4
haloalkylcarbonyl, C4-C7 cycloalkylcarbonyl, C2-05 alkoxycarbonyl, C3-05
alkoxycarbonylalkyl, C2-05 alkylaminocarbonyl or C3-05 dialkylaminocarbonyl;
each R14b is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-
C6
haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C1-C6 hydroxyalkyl, C2-C6
cyanoalkyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C3-C8 cycloalkenyl, C3-C8
halocycloalkenyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C4-C10
halocycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C5-C10 alkylcycloalkylalkyl,
C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C4-C10 cycloalkoxyalkyl, C3-C8
alkoxyalkoxyalkyl, C2-C6 alkylthioalkyl, C2-C6 alkylsulfinylalkyl, C2-C6
alkylsulfonylalkyl, C2-C6 alkylaminoalkyl, C2-C6 haloalkylaminoalkyl, C3-C8
dialkylaminoalkyl or C4-C10 cycloalkylaminoalkyl, each optionally substituted
with
up to 1 substituent selected from cyano, hydroxy, nitro, C2-C4 alkylcarbonyl,
C2-C4
alkoxycarbonyl, C3-C15 trialkylsilyl, C3-C15 halotrialkylsilyl and
pyrimidinyl; or
R14a and R14b are taken together to form a 4- to 6-membered fully saturated
heterocyclic
ring, each ring containing ring members, in addition to the connecting
nitrogen atom,
selected from carbon atoms and up to 2 heteroatoms independently selected from
up
to 2 0, up to 2 S and up to 2 N atoms, each ring optionally substituted with
up to 3
substituents independently selected from halogen and C1-C3 alkyl;
each R15 is independently H, cyano, halogen, methyl, methoxy, methylthio or
methoxycarbonyl;
each R16 is independently hydroxy or NR20aR20b; or C1-C4 alkoxy, C2-C4
alkenyloxy,
C2-C4 alkynyloxy, C2-C4 alkylcarbonyloxy, C2-05 alkoxycarbonyloxy, C2-05
alkylaminocarbonyloxy or C3-05 dialkylaminocarbonyloxy, each optionally
substituted with up to 1 substituent selected from cyano, halogen, hydroxy and
C(=0)0H;
each R17 is independently H, methyl, methoxy or methylthio;
each R18a and R18b is independently H or C1-C4 alkyl; or
R18a and R18b are taken together to form a 5- to 6-membered fully saturated
heterocyclic
ring, each ring containing ring members, in addition to the connecting
nitrogen atom,
selected from carbon atoms and up to 2 heteroatoms independently selected from
up
to 2 0, up to 2 S and up to 2 N atoms, each ring optionally substituted with
up to 2
methyl groups;
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
8
each R19 is independently amino, cyano, halogen, hydroxy, nitro, -SH, C1-C4
alkyl, C1-C4
haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C4 alkoxy, C1-C4
haloalkoxy,
C2-C4 alkoxyalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl,
C1-C4 haloalkylsulfonyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-05
alkoxycarbonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-05
alkylaminocarbonyl,
C3-05 dialkylaminocarbonyl, C3-05 alkylthioalkylcarbonyl, C3-C15 trialkylsily,
C3-C15 halotrialkylsilyl, C(R21)=N0R22 or C(R23)=NR24;
each U is independently a direct bond, C(=0)0, C(=0)N(R25) or C(=S)N(R26),
wherein
the atom to the left is connected to G, and the atom to the right is connected
to V;
each V is independently a direct bond; or C1-C6 alkylene, C2-C6 alkenylene, C3-
C6
alkynylene, C3-C6 cycloalkylene or C3-C6 cycloalkenylene, wherein up to 1
carbon
atom is C(=0), each optionally substituted with up to 3 substituents
independently
selected from halogen, cyano, nitro, hydroxy, C1-C2 alkyl, C1-C2 haloalkyl, C1-
C2
alkoxy and C1-C2 haloalkoxy;
each Q is independently phenyl or phenoxy, each optionally substituted with up
to 2
substituents independently selected from R27; or
each Q is independently a 5- to 6-membered heteroaromatic ring, each ring
containing ring
members selected from carbon atoms and 1 to 4 heteroatoms independently
selected
from up to 2 0, up to 2 S and up to 4 N atoms, each ring optionally
substituted with
up to 2 substituents independently selected from R27; or
each Q is independently a 3- to 7-membered nonaromatic heterocyclic ring, each
ring
containing ring members selected from carbon atoms and 1 to 4 heteroatoms
independently selected from up to 2 0, up to 2 S and up to 4 N atoms, wherein
up to
2 ring members are independently selected from C(=0), C(=S), S(=0) and S(=0)2,
each ring optionally substituted with up to 2 substituents independently
selected from
R27;
each R20a is independently H, C1-C4 alkyl or C2-C4 alkylcarbonyl;
each R20b is independently H, cyano, C1-05 alkyl, C2-05 alkylcarbonyl, C2-05
haloalkylcarbonyl, C4-C7 cycloalkylcarbonyl, C2-05 alkoxycarbonyl, C3-05
alkoxycarbonylalkyl, C2-05 alkylaminocarbonyl or C3-05 dialkylaminocarbonyl;
or
R20a and R20b are taken together to form a 5- to 6-membered fully saturated
heterocyclic
ring, each ring containing ring members, in addition to the connecting
nitrogen atom,
selected from carbon atoms and up to 2 heteroatoms independently selected from
up
to 2 0, up to 2 5 and up to 2 N atoms, each ring optionally substituted with
up to 2
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
9
methyl groups;
each R21 and R23 is independently H, cyano, halogen, C1-C3 alkyl, C1-C3
haloalkyl,
C3-C6 cycloalkyl or C1-C3 alkoxy; or phenyl optionally substituted with up to
2
substituents independently selected from halogen and C1-C3 alkyl;
each R22 is independently H, C1-05 alkyl, C1-05 haloalkyl, C2-05 alkenyl, C2-
05
haloalkenyl, C2-05 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-05
alkylcarbonyl or C2-05 alkoxycarbonyl; or
each R22 is phenyl optionally substituted with up to 2 substituents
independently selected
halogen and C1-C3 alkyl; or a 5- to 6-membered fully saturated heterocyclic
ring,
each ring containing ring members selected from carbon atoms and up to 2
heteroatoms independently selected from up to 2 0, up to 2 S and up to 2 N
atoms,
each ring optionally substituted with up to 2 substituents independently
selected from
halogen and C1-C3 alkyl;
each R24 is independently H, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C4
alkoxy, C2-C4
alkylcarbonyl or C2-C4 alkoxycarbonyl;
each R25 and R26 is independently H, cyano, hydroxy, C1-C4 alkyl, C1-C4
haloalkyl,
C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-C4 alkoxycarbonyl or C2-C4
haloalkoxycarbonyl;
each R27 is independently halogen, cyano, hydroxy, nitro, C1-C4 alkyl, C1-C4
haloalkyl,
C2-C4 alkenyl, C1-C4 alkoxy, C2-C4 alkylcarbonyl or C2-C4 alkoxycarbonyl;
Z is a direct bond, 0, 5(=0)m, N(R28), C(=0), C(=0)0, C(=0)N(R28), NR28C(=0),
N(R28)C(=0)N(R28), N(R28)C(=S)N(R28), 0C(=0)N(R28), N(R28)C(=0)0,
S(0)2N(R28), N(R28)S(=0)2 or N(R28)S(0)2N(R28), wherein the atom to the right
is
connected to L;
each R28 is independently H, C1-C3 alkyl, C1-C3 alkoxy, C2-C3 alkylcarbonyl or
C2-C3
alkoxycarbonyl; and
m is 0, 1 or 2; and
(b) at least one additional fungicidal compound;
provided that:
(a) when A1 is N(R7a), 0 or S, then A2 is a direct bond or CR6eR6f; and
(b) when A2 is N(R7b), 0 or S; then A1 is cR6cR6d.
This invention also relates to a composition comprising: (a) at least one
compound selected
from the compounds of Formula 1 described above, N-oxides, and salts thereof;
and at least one
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
invertebrate pest control compound or agent.
This invention also relates to a composition comprising one of the aforesaid
compositions
comprising component (a) and at least one additional component selected from
the group
consisting of surfactants, solid diluents and liquid diluents.
5
This invention also relates to a method for controlling plant diseases caused
by fungal plant
pathogens comprising applying to the plant or portion thereof, or to the plant
seed, a fungicidally
effective amount of one of the aforesaid compositions.
The aforedescribed method can also be described as a method for protecting a
plant or plant
seed from diseases caused by fungal pathogens comprising applying a
fungicidally effective
10
amount of one of the aforesaid compositions to the plant (or portion thereof)
or plant seed (directly
or through the environment (e.g., growing medium) of the plant or plant seed).
This invention also relates to a compound of Formula 1 described above, a
tautomer, an
N-oxide or salt thereof.
DETAILS OF THE INVENTION
As used herein, the terms "comprises," "comprising," "includes," "including,"
"has,"
"having," "contains," "containing," "characterized by" or any other variation
thereof, are intended
to cover a non-exclusive inclusion, subject to any limitation explicitly
indicated. For example, a
composition, mixture, process, method, article, or apparatus that comprises a
list of elements is
not necessarily limited to only those elements but may include other elements
not expressly listed
or inherent to such composition, mixture, process, method, article, or
apparatus.
The transitional phrase "consisting of' excludes any element, step, or
ingredient not
specified. If in the claim, such would close the claim to the inclusion of
materials other than those
recited except for impurities ordinarily associated therewith. When the phrase
"consisting of'
appears in a clause of the body of a claim, rather than immediately following
the preamble, it
limits only the element set forth in that clause; other elements are not
excluded from the claim as
a whole.
The transitional phrase "consisting essentially of' is used to define a
composition, method
or apparatus that includes materials, steps, features, components, or
elements, in addition to those
literally disclosed, provided that these additional materials, steps,
features, components, or
elements do not materially affect the basic and novel characteristic(s) of the
claimed invention.
The term "consisting essentially of' occupies a middle ground between
"comprising" and
"consisting of'.
Where applicants have defined an invention or a portion thereof with an open-
ended term
such as "comprising," it should be readily understood that (unless otherwise
stated) the description
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
11
should be interpreted to also describe such an invention using the terms
"consisting essentially
of' or "consisting of."
Further, unless expressly stated to the contrary, "or" refers to an inclusive
or and not to an
exclusive or. For example, a condition A or B is satisfied by any one of the
following: A is true
(or present) and B is false (or not present), A is false (or not present) and
B is true (or present),
and both A and B are true (or present).
Also, the indefinite articles "a" and "an" preceding an element or component
of the
invention are intended to be nonrestrictive regarding the number of instances
(i.e. occurrences) of
the element or component. Therefore "a" or "an" should be read to include one
or at least one,
and the singular word form of the element or component also includes the
plural unless the number
is obviously meant to be singular.
The term "agronomic" refers to the production of field crops such as for food
and fiber and
includes the growth of maize or corn, soybeans and other legumes, rice, cereal
(e.g., wheat, oats,
barley, rye and rice), leafy vegetables (e.g., lettuce, cabbage, and other
cole crops), fruiting
vegetables (e.g., tomatoes, pepper, eggplant, crucifers and cucurbits),
potatoes, sweet potatoes,
grapes, cotton, tree fruits (e.g., pome, stone and citrus), small fruit (e.g.,
berries and cherries) and
other specialty crops (e.g., canola, sunflower and olives).
The term "nonagronomic" refers to other than field crops, such as
horticultural crops (e.g.,
greenhouse, nursery or ornamental plants not grown in a field), residential,
agricultural,
commercial and industrial structures, turf (e.g., sod farm, pasture, golf
course, lawn, sports field,
etc.), wood products, stored product, agro-forestry and vegetation management,
public health (i.e.
human) and animal health (e.g., domesticated animals such as pets, livestock
and poultry,
undomesticated animals such as wildlife) applications.
The term "crop vigor" refers to rate of growth or biomass accumulation of a
crop plant. An
.. "increase in vigor" refers to an increase in growth or biomass accumulation
in a crop plant relative
to an untreated control crop plant. The term "crop yield" refers to the return
on crop material, in
terms of both quantity and quality, obtained after harvesting a crop plant. An
"increase in crop
yield" refers to an increase in crop yield relative to an untreated control
crop plant.
The term "biologically effective amount" refers to the amount of a
biologically active
compound (e.g., a compound of Formula 1 or a mixture with at least one other
fungicidal
compound) sufficient to produce the desired biological effect when applied to
(i.e. contacted with)
a fungus to be controlled or its environment, or to a plant, the seed from
which the plant is grown,
or the locus of the plant (e.g., growth medium) to protect the plant from
injury by the fungal
disease or for other desired effect (e.g., increasing plant vigor).
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
12
As referred to in the present disclosure and claims, "plant" includes members
of Kingdom
Plantae, particularly seed plants (Spermatopsida), at all life stages,
including young plants (e.g.,
germinating seeds developing into seedlings) and mature, reproductive stages
(e.g., plants
producing flowers and seeds). Portions of plants include geotropic members
typically growing
beneath the surface of the growing medium (e.g., soil), such as roots, tubers,
bulbs and corms, and
also members growing above the growing medium, such as foliage (including
stems and leaves),
flowers, fruits and seeds.
As referred to herein, the term "seedling", used either alone or in a
combination of words
means a young plant developing from the embryo of a seed.
As referred to herein, the term "broadleaf' used either alone or in words such
as "broadleaf
crop" means dicot or dicotyledon, a term used to describe a group of
angiosperms characterized
by embryos having two cotyledons.
As referred to in this disclosure, the terms "fungal pathogen" and "fungal
plant pathogen"
include pathogens in the Ascomycota, Basidiomycota and Zygomycota phyla, and
the fungal-like
Oomycota class that are the causal agents of a broad spectrum of plant
diseases of economic
importance, affecting ornamental, turf, vegetable, field, cereal and fruit
crops. In the context of
this disclosure, "protecting a plant from disease" or "control of a plant
disease" includes
preventative action (interruption of the fungal cycle of infection,
colonization, symptom
development and spore production) and/or curative action (inhibition of
colonization of plant host
tissues).
As used herein, the term "mode of action" (MOA) is as define by the Fungicide
Resistance
Action Committee (FRAC), and is used to distinguish fungicides according to
their biochemical
mode of action in the biosynthetic pathways of plant pathogens, and their
resistance risk.
FRAC-defined modes of actions include (A) nucleic acids metabolism, (B)
cytoskeleton and
motor protein, (C) respiration, (D) amino acids and protein synthesis, (E)
signal transduction, (F)
lipid synthesis or transport and membrane integrity or function, (G) sterol
biosynthesis in
membranes, (H) cell wall biosynthesis, (I) melanin synthesis in cell wall, (P)
host plant defense
induction, (U) unknown mode of action, (M) chemicals with multi-site activity
and (BM)
biologicals with multiple modes of action. Each mode of action (i.e. letters A
through BM)
contain one or more subgroups (e.g., A includes subgroups Al, A2, A3 and A4)
based either on
individual validated target sites of action, or in cases where the precise
target site is unknown,
based on cross resistance profiles within a group or in relation to other
groups. Each of these
subgroups (e.g., Al, A2, A3 and A4) is assigned a FRAC code which is a number
and/or letter.
For example, the FRAC code for subgroup Al is 4. Additional information on
target sites and
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
13
FRAC codes can be obtained from publicly available databases maintained, for
example, by
FRAC.
As used herein, the term "cross resistance" refers to the phenomenon that
occurs when a
pathogen develops resistance to one fungicide and simultaneously becomes
resistant to one or
more other fungicides. These other fungicides are typically, but not always,
in the same chemical
class or have the same target site of action, or can be detoxified by the same
mechanism.
In the above recitations, the term "alkyl", used either alone or in compound
words such as
"alkylthio" or "haloalkyl" includes straight-chain and branched alkyl, such
as, methyl, ethyl,
n-propyl, i-propyl, and the different butyl, pentyl and hexyl isomers.
"Alkenyl" includes straight-
chain and branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the
different butenyl,
pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such as 1,2-
propadienyl and
2,4-hexadienyl. "Alkynyl" includes straight-chain and branched alkynes such as
ethynyl,
1-propynyl, 2-propynyl, and the different butynyl, pentynyl and hexynyl
isomers. "Alkynyl" can
also include moieties comprised of multiple triple bonds such as 2,5-
hexadiynyl. "Alkylene"
.. denotes a straight-chain or branched alkanediyl. Examples of "alkylene"
include CH2, CH2CH2,
CH(CH3), CH2CH2CH2, CH2CH(CH3), and the different butylene isomers.
"Alkenylene"
denotes a straight-chain or branched alkenediyl containing one olefinic bond.
Examples of
"alkenylene" include CH=CH, CH2CH=CH, CH=C(CH3) and the different butenylene
isomers.
"Alkynylene" denotes a straight-chain or branched alkynediyl containing one
triple bond.
Examples of "alkynylene" include CH2CC, CCCH2, and the different butynylene,
pentynylene
or hexynylene isomers. The term "cycloalkylene" denotes a cycloalkanediyl
ring. Examples of
"cycloalkylene" include cyclobutanediyl, cyclopentanediyl and cyclohexanediyl.
The term
"cycloalkenylene" denotes a cycloalkenediyl ring containing one olefinic bond.
Examples of
"cycloalkenylene" include cyclopropenediyl and cyclopentenediyl.
"Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, i-propyloxy, and
the
different butoxy, pentoxy and hexyloxy isomers. "Alkenyloxy" includes straight-
chain and
branched alkenyl attached to and linked through an oxygen atom. Examples of
"alkenyloxy"
include H2C=CHCH20 and CH3CH=CHCH20. "Alkynyloxy" includes straight-chain and
branched alkynyl attached to and linked through an oxygen atom. Examples of
"alkynyloxy"
include HCCCH20 and CH3CCCH20.
The term "alkylthio" includes straight-chain and branched alkylthio moieties
such as
methylthio, ethylthio, and the different propylthio and butylthio isomers.
"Alkylsulfinyl" includes
both enantiomers of an alkylsulfinyl group. Examples of "alkylsulfinyl"
include CH3S(=0),
CH3CH2S(=0), CH3CH2CH2S(=0), (CH3)2CHS(=0), and the different butylsulfinyl
isomers.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
14
Examples of "alkylsulfonyl" include CH3S(=0)2, CH3CH2S(=0)2, CH3CH2CH2S(=0)2,
(CH3)2CHS(=0)2, and the different butylsulfonyl isomers. "Alkenylthio"
includes straight-chain
and branched alkenyl attached to and linked through a sulfur atom. Examples of
"alkenylthio"
include H2C=CHCH2S and CH3CH=CHCH2S. "Alkenylsulfinyl" includes both
enantiomers of
an alkenylsulfinyl group.
Examples of "alkenylsulfinyl" include H2C=CHCH2S(=0),
CH3CH=CHCH2S(=0), (CH3)2C=CHCH2S(=0). Examples of "alkenylsulfonyl" include
CH3CH=CHS(=0)2, (CH3)2C=CHCH2S(=0)2. "Alkynylthio" includes straight-chain and
branched alkynyl attached to and linked through a sulfur atom. Examples of
"alkynylthio" include
HCCCH2S and CH3CCCH2S. "Alkynylsulfinyl" includes both enantiomers of an
alkynylsulfinyl group.
Examples of "alkynylsulfinyl" include HCCCH2S(=0),
CH3CCCH2S (=0).
Examples of "alkynylsulfonyl" include CH3CCS (=0)2,
CH3CCCH2S(-0)2.
"Alkylthioalkyl" denotes alkylthio substitution on alkyl. Examples of
"alkylthioalkyl"
include CH3SCH2, CH3SCH2CH2, CH3CH2SCH2, CH3CH2CH2SCH2 and CH3CH2SCH2CH2;
"alkylsulfinylalkyl" and "alkylsulfonylalkyl" include the corresponding
sulfoxides and sulfones,
respectively.
"(Alkylthio)carbonyl" denotes a straight-chain or branched alkylthio group
bonded to a
C(=0) moiety. Examples of "(alkylthio)carbonyl" include CH3SC(=0),
CH3CH2CH2SC(=0)
and (CH3)2CHSC(=0). The terms "(alkenylthio)carbonyl" and
"(alkynylthio)carbonyl" are
likewise defined. Examples of "(alkenylthio)carbonyl" include H2C=CHCH2SC(=0)
and
CH3CH2CH=CHSC(=0). Examples of "(alkynylthio)carbonyl" include HCCCH2SC(=0)
and
CH3CCCH2SC(=0).
"Alkyl(thiocarbonyl)" denotes a straight-chain or branched alkyl group bonded
to a C(=S)
moiety. Examples of "alkyl(thiocarbonyl)" include CH3CH2C(=S), CH3CH2CH2C(=S)
and
(CH3)2CHCH2C(=S). The terms "alkenyl(thiocarbonyl)" and
"alkynyl(thiocarbonyl)" are
likewise defined. Examples of "alkenyl(thiocarbonyl)" include
H2C=CHCH2CH2C(=S) and
CH3CH2CH=CHC(=S). Examples of "alkynyl(thiocarbonyl)" include HCCCH2CH2C(=S)
and
CH3CCCH2C(=S).
"Alkylamino(thiocarbonyl)" denotes a straight-chain or branched alkylamino
group bonded
to a C(=S) moiety.
Examples of "alkylamino(thiocarbonyl)" include CH3NHC(=S),
CH3CH2CH2NHC(=S) and (CH3)2CHNHC(=S). The terms "alkenylamino(thiocarbonyl)"
and
"alkynylamino(thiocarbonyl)" are likewise defined. Examples of
"alkenylamino(thiocarbonyl)"
include H2C=CHCH2CH2NHC(=S) and CH3CH2CH=CHNHC(=S).
Examples of
"alkynylamino(thiocarbonyl)" include HCCCH2CH2NHC(=S) and CH3CCCH2NHC(=S).
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
"(Alkylthio)carbonylamino" denotes a straight-chain or branched alkylthio
group bonded to
a C(=0)NH moiety. Examples of "(alkylthio)carbonylamino" include
CH3CH2SC(=0)NH,
CH3CH2CH2SC(=0)NH and (CH3)2CHSC(=0)NH. The terms "(alkenylthio)carbonylamino"
and "(alkynylthio)carbonylamino" are likewise defined. Examples of
5 "(alkenylthio)carbonylamino include H2C=CHCH2SC(=0)NH and CH3CH=CHSC(=0)NH.
Examples of "(alkynylthio)carbonylamino" include HCCCH2CH2SC(=0)NH and
CH3CCCH2CH2SC(=0)NH.
"Alkylamino" includes an NH radical substituted with a straight-chain or
branched alkyl
group.
Examples of "alkylamino" include CH3CH2NH, CH3CH2CH2NH, and
10 (CH3)2CHCH2NH. Examples of "dialkylamino" include (CH3)2N, (CH3CH2CH2)2N
and
CH3CH2(CH3)N. "Alkylaminoalkyl" denotes alkylamino substitution on alkyl.
Examples of
"alkylaminoalkyl" include CH3NHCH2, CH3NHCH2CH2, CH3CH2NHCH2,
CH3CH2CH2CH2NHCH2 and CH3CH2NHCH2CH2.
"Alkylcarbonyl" denotes a straight-chain or branched alkyl group bonded to a
C(=0)
15 moiety.
Examples of "alkylcarbonyl" include CH3C(=0), CH3CH2CH2C(=0) and
(CH3)2CHC(=0). The terms "alkenylcarbonyl" and "alkynylcarbonyl" are likewise
defined.
Examples of "alkenylcarbonyl" include H2C=CHCH2C(=0) and CH3CH2CH=CHC(=0).
Examples of "alkynylcarbonyl" include HCCCH2C(=0) and CH3CCCH2C(=0).
"Alkoxycarbonyl" includes a C(=0) moiety substituted with a straight-chain or
branched alkoxy
group.
Examples of "alkoxycarbonyl" include CH30C(=0), CH3CH20C(=0),
CH3CH2CH20C(-0), (CH3)2CHOC(-0).
The terms "alkenyloxycarbonyl" and
"alkynyloxycarbonyl" are likewise defined. Examples of "alkenyloxycarbonyl"
include
H2C=CHCH20C(=0) and CH3CH2CH=CHOC(=0). Examples of "alkynyloxycarbonyl"
include HCCCH20C(=0) and CH3CCCH20C(=0).
"Alkylaminocarbonyl" denotes a straight-chain or branched alkyl group bonded
to a
NHC(=0) moiety.
Examples of "alkylaminocarbonyl" include CH3NHC(=0),
CH3CH2NHC(=0), CH3CH2CH2NHC(=0), (CH3)2CHNHC(=0). The terms
"alkenylaminocarbonyl" and "alkynylaminocarbonyl" are likewise defined.
Examples of
"alkenylaminocarbonyl" include H2C=CHCH2NHC(=0) and (CH3)2C=CHCH2NHC(=0).
Examples of "alkynylaminocarbonyl" include CH3CCNHC(=0) and CH3CCCH2NHC(=0).
Examples of "dialkylaminocarbonyl" include (CH3)2N(=0), (CH3CH2)2NC(=0),
CH3CH2(CH3)NC(=0), (CH3)2CH(CH3)NC(=0) and CH3CH2CH2(CH3)NC(=0).
The term "alkylcarbonylamino" denotes a straight-chain or branched alkyl group
bonded to
a C(=0)NH moiety. Examples of "alkylcarbonylamino" include CH3CH2C(=0)NH and
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
16
CH3CH2CH2C(=0)NH. The terms "alkenylcarbonylamino" and "alkynylcarbonylamino"
are
likewise defined. Examples of "alkenylcarbonylamino" include H2C=CHCH2C(=0)NH
and
(CH3)2C=CHCH2C(=0)NH.
Examples of "alkynylcarbonylamino" include
CH3CCCH(CH3)C(=0)NH and HCCCH2CH2C(=0)NH. The term "alkoxycarbonylamino"
denotes alkoxy bonded to a C(=0)NH moiety. Examples of "alkoxycarbonylamino"
include
CH30C(=0)NH and CH3CH20C(=0)NH.
The term "alkylaminocarbonylamino" denotes a straight-chain or branched alkyl
group
bonded to a NHC(=0)NH moiety. Examples of "alkylaminocarbonylamino" include
CH3CH2NHC(=0)NH and (CH3CH2)2CH2NHC(=0)NH.
The terms
"alkenylaminocarbonylamino" and "alkynylaminocarbonylamino" are likewise
defined.
Examples of "alkenylaminocarbonylamino" include H2C=CHCH2NHC(=0)NH and
(CH3)2C=CHCH2NHC(=0)NH.
Examples of "alkynylaminocarbonylamino" include
CH3CCCH(CH3)NHC(=0)NH and HCCCH2CH2NHC(=0)NH.
"Alkylsulfonylamino" denotes an NH radical substituted with alkylsulfonyl.
Examples of
"alkylsulfonylamino" include CH3CH2S(=0)2NH and (CH3)2CHS(=0)2NH. The terms
"alkenylsulfonylamino" and "alkynylsulfonylamino" are likewise defined.
Examples of
"alkenylsulfonylamino" include H2C=CHCH2CH2S(=0)2NH and (CH3)2C=CHCH2S(=0)2NH.
Examples of "alkynylsulfonylamino" include CH3CCCH(CH3)S(=0)2NH and
HCCCH2CH2S(=0)2NH. The term "alkylsulfonyloxy" denotes an alkylsulfonyl group
bonded
to an oxygen atom. Examples of "alkylsulfonyloxy" include CH3S(=0)20,
CH3CH2S(=0)20,
CH3CH2CH2S (=0)20, (CH3)2CHS (=0)20,
and the different butylsulfonyloxy,
pentylsulfonyloxy and hexylsulfonyloxy isomers.
"Alkylaminosulfonyl" denotes a straight-chain or branched alkyl group bonded
to a
NHS(=0)2 moiety. Examples of "alkylaminosulfonyl" include CH3CH2NHS(=0)2 and
(CH3)2CHNHS(=0)2. The terms "alkenylaminosulfonyl" and "alkynylaminosulfonyl"
are
likewise defined. Examples of "alkenylaminosulfonyl" include
H2C=CHCH2CH2NHS(=0)2 and
(CH3)2C=CHCH2NHS (=0)2. Examples of "alkynylaminosulfonyl"
include
CH3CCCH(CH3)NHS(=0)2 and HCCCH2CH2NHS(=0)2.
"Alkylaminosulfonylamino" denotes a straight-chain or branched alkyl group
bonded to a
NHS(=0)2NH moiety. Examples of "alkylaminosulfonylamino" include
CH3CH2NHS(=0)2NH
and (CH3)2CHNHS(=0)2NH.
The terms "alkenylaminosulfonylamino" and
"alkynylaminosulfonylamino" are likewise defined. Examples of
"alkenylaminosulfonylamino"
include H2C=CHCH2CH2NHS(=0)2NH and (CH3)2C=CHCH2NHS(=0)2NH. Examples of
"alkynylaminosulfonylamino" include CH3CCCH(CH3)NHS (=0)2NH
and
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
17
HCCCH2CH2NHS (=0)2NH.
"Alkoxyalkyl" denotes alkoxy substitution on alkyl. Examples of "alkoxyalkyl"
include
CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2OCH2 and CH3CH2OCH2CH2.
"Alkoxyalkoxy" denotes alkoxy substitution on another alkoxy moiety.
"Alkoxyalkoxyalkyl"
denotes alkoxyalkoxy substitution on alkyl. Examples of "alkoxyalkoxyalkyl"
include
CH3OCH2OCH2, CH3OCH2OCH2CH2 and CH3CH2OCH2OCH2.
The term "alkylcarbonyloxy" denotes a straight-chain or branched alkyl bonded
to a
C(=0)0 moiety.
Examples of "alkylcarbonyloxy" include CH3CH2C(=0)0 and
(CH3)2CHC(=0)0. The terms "alkenylcarbonyloxy" and "alkynylcarbonyloxy" are
likewise
defined.
Examples of "alkenylcarbonyloxy" include H2C=CHCH2CH2C(=0)0 and
(CH3)2C¨CHCH2C(-0)0. Examples of "alkynylcarbonyloxy"
include
CH3CCCH(CH3)C(=0)0 and HCCCH2CH2C(=0)0. The term "alkoxycarbonyloxy" denotes
a straight-chain or branched alkoxy bonded to a C(=0)0 moiety.
Examples of
"alkoxycarbonyloxy" include CH3CH2CH20C(=0)0 and (CH3)2CHOC(=0)0. The term
"alkoxycarbonylalkyl" denotes alkoxycarbonyl substitution on alkyl. Examples
of
"alkoxycarbonylalkyl" include CH3CH20C(=0)CH2, (CH3)2CHOC(=0)CH2 and
CH30C(=0)CH2CH2. The term "alkylaminocarbonyloxy" denotes a straight-chain or
branched
alkylaminocarbonyl attached to and linked through an oxygen atom.
Examples of
"alkylaminocarbonyloxy" include (CH3)2CHCH2NHC(=0)0 and CH3CH2NHC(=0)0. The
terms "alkenylaminocarbonyloxy" and "alkynylaminocarbonyloxy" are likewise
defined.
The term "alkylcarbonylthio" denotes a straight-chain or branched alkyl group
bonded to a
C(=0)S moiety.
Examples of "alkylcarbonylthio" include CH3CH2C(=0)S and
CH3CH2CH2C(-0)S.
"Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and
cyclohexyl.
The term "cycloalkylalkyl" denotes cycloalkyl substitution on an alkyl moiety.
Examples of
"cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other
cycloalkyl moieties
bonded to a straight-chain or branched alkyl group. The term "alkylcycloalkyl"
denotes alkyl
substitution on a cycloalkyl moiety and includes, for example,
ethylcyclopropyl,
i-propylcyclobutyl, methylcyclopentyl and methylcyclohexyl.
"Alkylcycloalkylalkyl" denotes
alkylcycloalkyl substitution on alkyl.
Examples of "alkylcycloalkylalkyl" include
methylcyclohexylmethyl and ethylcycloproylmethyl. "Cycloalkenyl" includes
groups such as
cyclopentenyl and cyclohexenyl as well as groups with more than one double
bond such as 1,3- or
1,4-cyclohexadienyl. The term "cycloalkylcycloalkyl" denotes cycloalkyl
substitution on another
cycloalkyl ring, wherein each cycloalkyl ring independently has from 3 to 7
carbon atom ring
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
18
members. Examples of cycloalkylcycloalkyl include cyclopropylcyclopropyl (such
as 1,1'-
bicyclopropy1-1-yl, 1, F-bicyclopropy1-2-y1),
cyclohexylcyclopentyl (such as 4-
cyclopentylcyclohexyl) and cyclohexylcyclohexyl (such as 1,1'-bicyclohexy1-1-
y1), and the
different cis- and trans-cycloalkylcycloalkyl isomers, (such as (1R,2S)-1,1'-
bicyclopropy1-2-y1
and (1R,2R)-1,1'-bicyclopropy1-2-y1).
The term "cycloalkoxy" denotes cycloalkyl attached to and linked through an
oxygen atom
including, for example, cyclopentyloxy and cyclohexyloxy. The term
"cycloalkoxyalkyl" denotes
cycloalkoxy substitution on an alkyl moiety. Examples of "cycloalkoxyalkyl"
include
cyclopropyloxymethyl, cyclopentyloxyethyl, and other cycloalkoxy groups bonded
to a
straight-chain or branched alkyl moiety.
The term "cycloalkylaminoalkyl" denotes cycloalkylamino substitution on an
alkyl group.
Examples of "cycloalkylaminoalkyl" include cyclopropylaminomethyl,
cyclopentylaminoethyl,
and other cycloalkylamino moieties bonded to a straight-chain or branched
alkyl group.
"Cycloalkylcarbonyl" denotes cycloalkyl bonded to a C(=0) group including, for
example,
cyclopropylcarbonyl and cyclopentylcarbonyl.
"Cycloalkylcarbonyloxy" denotes
cycloalkylcarbonyl attached to and linked through an oxygen atom.
Examples of
"cycloalkylcarbonyloxy" include cyclohexylcarbonyloxy and
cyclopentylcarbonyloxy. The term
"cycloalkoxycarbonyl" means cycloalkoxy bonded to a C(=0) group, for example,
cyclopropyloxycarbonyl and cyclopentyloxycarbonyl.
"Cycloalkylaminocarbonylamino"
denotes cycloalkylamino bonded to a C(=0)NH group, for example,
cyclopentylaminocarbonylamino and cyclohexylaminocarbonylamino.
The term "halogen", either alone or in compound words such as "haloalkyl", or
when used
in descriptions such as "alkyl substituted with halogen" includes fluorine,
chlorine, bromine or
iodine. Further, when used in compound words such as "haloalkyl", or when used
in descriptions
such as "alkyl substituted with halogen" said alkyl may be partially or fully
substituted with
halogen atoms which may be the same or different. Examples of "haloalkyl" or
"alkyl substituted
with halogen" include CF3, C1CH2, CF3CH2 and CF3CC12. The terms "haloalkenyl",
"haloalkynyl" "haloalkoxy", "haloalkylsulfonyl", "halocycloalkyl", and the
like, are defined
analogously to the term "haloalkyl". Examples of "haloalkenyl" include
C12C=CHCH2 and
CF3CH2CH=CHCH2. Examples of "haloalkynyl" include HCCCHC1, CF3CC, CC13CC and
FCH2CCCH2. Examples of "haloalkoxy" include CF30, CC13CH20, F2CHCH2CH20 and
CF3CH20. Examples of "haloalkylsulfonyl" include CF3S(=0)2, CC13S(=0)2,
CF3CH2S(=0)2
and CF3CF2S(=0)2.
Examples of "halocycloalkyl" include 2-chlorocyclopropyl,
2-fluorocyclobutyl, 3-bromocyclopentyl and 4-chorocyclohexyl.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
19
"Cyanoalkyl" denotes an alkyl group substituted with one cyano group. Examples
of
"cyanoalkyl" include NCCH2, NCCH2CH2 and CH3CH(CN)CH2. "Hydroxyalkyl" denotes
an
alkyl group substituted with one hydroxy group. Examples of "hydroxyalkyl"
include
HOCH2CH2, CH3CH2(OH)CH and HOCH2CH2CH2CH2.
"Trialkylsily1" includes 3 branched and/or straight-chain alkyl radicals
attached to and
linked through a silicon atom, such as trimethylsilyl, triethylsilyl and tert-
butyldimethylsilyl. The
term "halotrialkylsily1" is likewise defined.
Examples of "halotrialkylsily1" include
trifluormethylsilyl and trichloromethylsilyl.
The total number of carbon atoms in a substituent group is indicated by the
"Ci-Ci" prefix
where i and j are numbers from 1 to 15. For example, C1-C4 alkylsulfonyl
designates
methylsulfonyl through butylsulfonyl; C2 alkoxyalkyl designates CH3OCH2; C3
alkoxyalkyl
designates, for example, CH3CH(OCH3), CH3OCH2CH2 or CH3CH2OCH2; and C4
alkoxyalkyl
designates the various isomers of an alkyl group substituted with an alkoxy
group containing a
total of four carbon atoms, examples including CH3CH2CH2OCH2 and
CH3CH2OCH2CH2.
Generally when a molecular fragment (i.e. radical) is denoted by a series of
atom symbols
(e.g., C, H, N, 0 and S) the implicit point or points of attachment will be
easily recognized by
those skilled in the art. In some instances herein, particularly when
alternative points of
attachment are possible, the point or points of attachment may be explicitly
indicated by a hyphen
The term "unsubstituted" in connection with a group such as a ring or ring
system means
the group does not have any substituents other than its one or more
attachments to the remainder
of Formula 1. The term "optionally substituted" means that the number of
substituents can be
zero. Unless otherwise indicated, optionally substituted groups may be
substituted with as many
optional substituents as can be accommodated by replacing a hydrogen atom with
a non-hydrogen
substituent on any available carbon or nitrogen atom. Commonly, the number of
optional
substituents (when present) ranges from 1 to 3. As used herein, the term
"optionally substituted"
is used interchangeably with the phrase "substituted or unsubstituted" or with
the term
"(un) substituted."
The number of optional substituents may be restricted by an expressed
limitation. For
example, the phrase "optionally substituted with up to 3 substituents
independently selected from
R13" means that 0, 1, 2 or 3 substituents can be present (if the number of
potential connection
points allows). When a range specified for the number of substituents (e.g., x
being an integer
from 0 to 3 in Exhibit A) exceeds the number of positions available for
substituents on a ring (e.g.,
1 position available for (R13)x on G-7 in Exhibit A), the actual higher end of
the range is
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
recognized to be the number of available positions.
When a compound is substituted with a substituent bearing a subscript that
indicates the
number of said substituents can vary (e.g., (R13)x in Exhibit A wherein x is 1
to 3), then said
substituents are independently selected from the group of defined
substituents, unless otherwise
5 indicated. When a variable group is shown to be optionally attached to a
position, for example
(R13)x in Exhibit A wherein x may be 0, then hydrogen may be at the position
even if not recited
in the definition of the variable group.
The dotted line in rings depicted in the present description (e.g., the rings
G-44, G-45, G-48
and G-49 shown in Exhibit A) represents that the bond indicated can be a
single bond or double
10 bond.
Naming of substituents in the present disclosure uses recognized terminology
providing
conciseness in precisely conveying to those skilled in the art the chemical
structure. For sake of
conciseness, locant descriptors may be omitted.
Unless otherwise indicated, a "ring" or "ring system" as a component of
Formula 1 (e.g., G)
15 is carbocyclic or heterocyclic. The term "ring system" denotes two or
more connected rings. The
term "spirocyclic ring system" denotes a ring system consisting of two rings
connected at a single
atom (so the rings have a single atom in common). The term "bicyclic ring
system" denotes a
ring system consisting of two rings sharing two or more common atoms. In a
"fused bicyclic ring
system" the common atoms are adjacent, and therefore the rings share two
adjacent atoms and a
20 bond connecting them.
The term "ring member" refers to an atom (e.g., C, 0, N or S) or other moiety
(e.g., C(=0),
C(=S), S(=0) and S(=0)2) forming the backbone of a ring or ring system. The
term "aromatic"
indicates that each of the ring atoms is essentially in the same plane and has
a p-orbital
perpendicular to the ring plane, and that (4n + 2) it electrons, where n is a
positive integer, are
associated with the ring to comply with Hiickel' s rule
The term "carbocyclic ring" denotes a ring wherein the atoms forming the ring
backbone
are selected only from carbon. Unless otherwise indicated, a carbocyclic ring
can be a saturated,
partially unsaturated, or fully unsaturated ring. When a fully unsaturated
carbocyclic ring satisfies
Hiickel's rule, then said ring is also called an "aromatic ring". "Saturated
carbocyclic" refers to a
ring having a backbone consisting of carbon atoms linked to one another by
single bonds; unless
otherwise specified, the remaining carbon valences are occupied by hydrogen
atoms.
As used herein, the term "partially unsaturated ring" or "partially
unsaturated heterocycle"
refers to a ring which contains unsaturated ring atoms and one or more double
bonds but is not
aromatic.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
21
The terms "heterocyclic ring" or "heterocycle" denotes a ring wherein at least
one of the
atoms forming the ring backbone is other than carbon. Unless otherwise
indicated, a heterocyclic
ring can be a saturated, partially unsaturated, or fully unsaturated ring.
When a fully unsaturated
heterocyclic ring satisfies Hiickel' s rule, then said ring is also called a
"heteroaromatic ring" or
aromatic heterocyclic ring. "Saturated heterocyclic ring" refers to a
heterocyclic ring containing
only single bonds between ring members.
Unless otherwise indicated, heterocyclic rings and ring systems are attached
to the
remainder of Formula 1 through any available carbon or nitrogen atom by
replacement of a
hydrogen on said carbon or nitrogen atom.
Compounds of this invention can exist as one or more stereoisomers.
Stereoisomers are
isomers of identical constitution but differing in the arrangement of their
atoms in space and
include enantiomers, diastereomers, cis- and trans-isomers (also known as
geometric isomers)
and atropisomers. Atropisomers result from restricted rotation about single
bonds where the
rotational barrier is high enough to permit isolation of the isomeric species.
One skilled in the art
will appreciate that one stereoisomer may be more active and/or may exhibit
beneficial effects
when enriched relative to the other stereoisomer(s) or when separated from the
other
stereoisomer(s). Additionally, the skilled artisan knows how to separate,
enrich, and/or to
selectively prepare said stereoisomers. For a comprehensive discussion of all
aspects of
stereoisomerism, see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of
Organic
Compounds, John Wiley & Sons, 1994.
Compounds of this invention may be present as a mixture of stereoisomers,
individual
stereoisomers, or as an optically active form. For example, when T is T-3,
then Formula 1
compounds contain at least one double bond and the configuration of
substituents about that
double bond can be (Z) or (E) (cis or trans), or a mixture thereof. In the
context of the present
disclosure and claims, a wavy bond (e.g., as shown in the T-3 moiety in the
Summary of the
Invention) indicates a single bond which is linked to an adjacent double bond
wherein the
geometry about the adjacent double bond is either (Z)-configuration (syn-
isomer or cis-isomer) or
(E)-configuration (anti-isomer or trans-isomer), or a mixture thereof. That
is, a wavy bond
represents an unspecified (Z)- or (E)- (cis- or trans-) isomer, or mixture
thereof. In addition, the
compounds of the present invention can contain one or more chiral centers and
therefore exist in
enantiomeric and diastereomeric forms. Unless the structural formula or the
language of this
application specifically designate a particular cis- or trans-isomer, or a
configuration of a chiral
center, the scope of the present invention is intended to cover all such
isomers per se, as well as
mixtures of cis- and trans-isomers, mixtures of diastereomers and racemic
mixtures of
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
22
enantiomers (optical isomers) as well.
This invention also includes compounds of Formula 1 wherein one stereoisomer
is enriched
relative to the other stereoisomer(s). Of note are compounds of Formula 1
wherein T is T-3 and
the substituents attached to the double bond in the T-3 moiety are in a
predominately (Z)-
configuration, or predominately an (E)-configuration. The ratio of the (Z)- to
(E)-isomers in any
compounds of Formula 1, whether produced stereoselectivity or non-
stereoselectivity, may take
on a broad range of values. For example, compounds of Formula 1 may comprise
from about 10
to 90 percent by weight of the (Z)-isomer to about 90 to 10 percent by weight
of the (E)-isomer.
In other embodiments, Formula 1 compounds may contain from about 15 to 85
percent by weight
of the (Z)-isomer and about 85 to 15 percent by weight of the (E)-isomer; in
another embodiment,
the mixture contains about 25 to 75 percent by weight of the (Z)-isomer and
about 75 to 25 percent
by weight of the (E)-isomer; in another embodiment, the mixture contains about
35 to 65 percent
by weight of the (Z)-isomer and about 65 to 35 percent by weight of the (E)-
isomer; in another
embodiment, the mixture contains about 45 to 55 percent by weight of the (Z)-
isomer and about
55 to 45 percent by weight of the (E)-isomer. These percentages by weight are
based on the total
weight of the composition, and it will be understood that the sum of the
weight percent of the (Z)-
isomer and the (E)-isomer is 100 weight percent. In other words, compounds of
Formula 1 might
contain 65 percent by weight of the (Z)-isomer and 35 percent by weight of the
(E)-isomer, or
vice versa.
In addition, this invention includes compounds that are enriched compared to
the racemic
mixture in an enantiomer of Formula 1. Also included are the essentially pure
enantiomers of
compounds of Formula 1. When enantiomerically enriched, one enantiomer is
present in greater
amounts than the other, and the extent of enrichment can be defined by an
expression of
enantiomeric excess ("ee"), which is defined as (2x-1)- 100%, where x is the
mole fraction of the
dominant enantiomer in the mixture (e.g., an ee of 20% corresponds to a 60:40
ratio of
enantiomers).
Preferably the compositions of this invention have at least a 50% enantiomeric
excess; more
preferably at least a 75% enantiomeric excess; still more preferably at least
a 90% enantiomeric
excess; and the most preferably at least a 94% enantiomeric excess of the more
active isomer. Of
particular note are enantiomerically pure embodiments of the more active
isomer.
Compounds of this invention can exist as one or more conformational isomers
due to
restricted rotation about an amide bond (e.g., C(=0)-N) in Formula 1. This
invention comprises
mixtures of conformational isomers. In addition, this invention includes
compounds that are
enriched in one conformer relative to others.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
23
This invention comprises all stereoisomers, conformational isomers and
mixtures thereof in
all proportions as well as isotopic forms such as deuterated compounds.
One skilled in the art will appreciate that not all nitrogen containing
heterocycles can form
N-oxides since the nitrogen requires an available lone pair for oxidation to
the oxide; one skilled
in the art will recognize those nitrogen-containing heterocycles which can
form N-oxides. One
skilled in the art will also recognize that tertiary amines can form N-oxides.
Synthetic methods
for the preparation of N-oxides of heterocycles and tertiary amines are very
well known by one
skilled in the art including the oxidation of heterocycles and tertiary amines
with peroxy acids
such as peracetic and rn-chloroperbenzoic acid (MCPBA), hydrogen peroxide,
alkyl
hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes
such as
dimethyldioxirane. These methods for the preparation of N-oxides have been
extensively
described and reviewed in the literature, see for example: T. L. Gilchrist in
Comprehensive
Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M.
Tisler and
B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J.
Boulton and
A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in
Advances in
Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic
Press; M. Tisler and
B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A. R.
Katritzky and
A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G.
Werstiuk in
Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and
A. J. Boulton, Eds.,
Academic Press.
One skilled in the art recognizes that because in the environment and under
physiological
conditions salts of chemical compounds are in equilibrium with their
corresponding nonsalt forms,
salts share the biological utility of the nonsalt forms. Thus a wide variety
of salts of the
compounds of Formula 1 are useful for control of plant diseases caused by
fungal plant pathogens
(i.e. are agriculturally suitable). The salts of the compounds of Formula 1
include acid-addition
salts with inorganic or organic acids such as hydrobromic, hydrochloric,
nitric, phosphoric,
sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic,
propionic, salicylic, tartaric,
4-toluenesulfonic or valeric acids. When a compound of Formula 1 contains an
acidic moiety
such as a carboxylic acid, salts also include those formed with organic or
inorganic bases such as
pyridine, triethylamine or ammonia, or amides, hydrides, hydroxides or
carbonates of sodium,
potassium, lithium, calcium, magnesium or barium. Accordingly, the present
invention comprises
compounds selected from Formula 1, N-oxides, and agriculturally suitable
salts, and solvates
thereof.
Compounds selected from Formula 1, stereoisomers, tautomers, N-oxides, and
salts thereof,
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
24
typically exist in more than one form, and Formula 1 thus includes all
crystalline and non-
crystalline forms of the compounds that Formula 1 represents. Non-crystalline
forms include
embodiments which are solids such as waxes and gums as well as embodiments
which are liquids
such as solutions and melts. Crystalline forms include embodiments which
represent essentially
a single crystal type and embodiments which represent a mixture of polymorphs
(i.e. different
crystalline types). The term "polymorph" refers to a particular crystalline
form of a chemical
compound that can crystallize in different crystalline forms, these forms
having different
arrangements and/or conformations of the molecules in the crystal lattice.
Although polymorphs
can have the same chemical composition, they can also differ in composition
due to the presence
or absence of co-crystallized water or other molecules, which can be weakly or
strongly bound in
the lattice. Polymorphs can differ in such chemical, physical and biological
properties as crystal
shape, density, hardness, color, chemical stability, melting point,
hygroscopicity, suspensibility,
dissolution rate and biological availability. One skilled in the art will
appreciate that a polymorph
of a compound represented by Formula 1 can exhibit beneficial effects (e.g.,
suitability for
preparation of useful formulations, improved biological performance) relative
to another
polymorph or a mixture of polymorphs of the same compound represented by
Formula 1.
Preparation and isolation of a particular polymorph of a compound represented
by Formula 1 can
be achieved by methods known to those skilled in the art including, for
example, crystallization
using selected solvents and temperatures. For a comprehensive discussion of
polymorphism see
R. Hilfiker, Ed., Polymorphism in the Pharmaceutical Industry, Wiley-VCH,
Weinheim, 2006.
One skilled in the art recognizes that compounds of Formula 1 can exist as
mixtures of
ketonic and solvated forms (e.g., hemiketals, ketals and hydrates) and each
are independently
interconvertible and agriculturally active. For example, ketones of Formula 11
(i.e. compounds
of Formula 1 wherein T is T-1) may exist in equilibrium with their
corresponding hydrates of
Formula 12 (i.e. compounds of Formula 1 wherein T is T-2, and R2aX and R2bY
are both OH).
In cases where the ketone group is in close proximity to an electron-
withdrawing group, such as
when R1 is a trifluoromethyl group, the equilibrium typically favors the
hydrate form.
0
HO OH
E R1
A I
A
11 12
This invention comprises all ketonic and solvated forms of Formula 1
compounds, and
mixtures thereof in all proportions. Unless otherwise indicated, reference to
a compound by one
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
tautomer description is to be considered to include all tautomers.
Additionally, some of the unsaturated rings and ring systems depicted in
Exhibit A can have
an arrangement of single and double bonds between ring members different from
that depicted.
Such differing arrangements of bonds for a particular arrangement of ring
atoms correspond to
5 different tautomers. For these unsaturated rings and ring systems, the
particular tautomer depicted
is to be considered representative of all the tautomers possible for the
arrangement of ring atoms
shown.
As described in the Summary of the Invention, an aspect of the present
invention is directed
at a composition comprising (a) at least one compound selected from Formula 1,
N-oxides, and
10 salts thereof, with (b) at least one additional fungicidal compound.
More particularly, Component
(b) is selected from the group consisting of
(bl) methyl benzimidazole carbamate (MBC) fungicides;
(b2) dicarboximide fungicides;
(b3) demethylation inhibitor (DMI) fungicides;
15 (b4) phenylamide (PA) fungicides;
(b5) amine/morpholine fungicides;
(b6) phospholipid biosynthesis inhibitor fungicides;
(b7) succinate dehydrogenase inhibitor (SDHI) fungicides;
(b8) hydroxy(2-amino-)pyrimidine fungicides;
20 (b9) anilinopyrimidine (AP) fungicides;
(b10) N-phenyl carbamate fungicides;
(1111) quinone outside inhibitor (QoI) fungicides;
(b12) phenylpyrrole (PP) fungicides;
(b13) azanaphthalene fungicides;
25 (b14) cell peroxidation inhibitor fungicides;
(b15) melanin biosynthesis inhibitor-reductase (MBI-R) fungicides;
(b16a) melanin biosynthesis inhibitor-dehydratase (MBI-D) fungicides;
(b16b) melanin biosynthesis inhibitor-polyketide synthase (MBI-P) fungicides;
(b17) keto reductase inhibitor (KRI) fungicides;
(b18) squalene-epoxidase inhibitor fungicides;
(b19) polyoxin fungicides;
(b20) phenylurea fungicides;
(b21) quinone inside inhibitor (QiI) fungicides;
(b22) benzamide and thiazole carboxamide fungicides;
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
26
(b23) enopyranuronic acid antibiotic fungicides;
(b24) hexopyranosyl antibiotic fungicides;
(b25) glucopyranosyl antibiotic: protein synthesis fungicides;
(b26) glucopyranosyl antibiotic fungicides;
(b27) cyanoacetamideoxime fungicides;
(b28) carbamate fungicides;
(b29) oxidative phosphorylation uncoupling fungicides;
(b30) organo tin fungicides;
(b31) carboxylic acid fungicides;
(b32) heteroaromatic fungicides;
(b33) phosphonate fungicides;
(b34) phthalamic acid fungicides;
(b35) benzotriazine fungicides;
(b36) benzene-sulfonamide fungicides;
(b37) pyridazinone fungicides;
(b38) thiophene-carboxamide fungicides;
(b39) complex I NADH oxido-reductase inhibitor fungicides;
(b40) carboxylic acid amide (CAA) fungicides;
(b41) tetracycline antibiotic fungicides;
(b42) thiocarbamate fungicides;
(b43) benzamide fungicides;
(b44) microbial fungicides;
(b45) quinone outside inhibitor, stigmatellin binding (QoSI) fungicides;
(b46) plant extract fungicides;
(b47) cyanoacrylate fungicides;
(b48) polyene fungicides;
(b49) oxysterol binding protein inhibitor (OSBPI) fungicides;
(b50) aryl-phenyl-ketone fungicides;
(b51) host plant defense induction fungicides;
(b52) multi-site activity fungicides;
(b53) biologicals with multiple modes of action;
(b54) fungicides other than fungicides of component (a) and components (Ill)
through
(b53); and
salts of compounds of (Ill) through (b54).
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
27
Of note are embodiments wherein component (b) comprises at least one
fungicidal
compound from each of two different groups selected from (b 1) through (b54).
"Methyl benzimidazole carbamate (MBC) fungicides (b1)" (FRAC code 1) inhibit
mitosis
by binding to 13-tubulin during microtubule assembly. Inhibition of
microtubule assembly can
disrupt cell division, transport within the cell and cell structure. Methyl
benzimidazole carbamate
fungicides include benzimidazole and thiophanate fungicides. The
benzimidazoles include
benomyl, carbendazim, fuberidazole and thiabendazole. The thiophanates include
thiophanate
and thiophanate-methyl.
"Dicarboximide fungicides (b2)" (FRAC code 2) inhibit a mitogen-activated
protein
(MAP)/histidine kinase in osmotic signal transduction. Examples include
chlozolinate,
dimethachlone, iprodione, procymidone and vinclozolin.
"Demethylation inhibitor (DMI) fungicides (b3)" (FRAC code 3) (Sterol
Biosynthesis
Inhibitors (SBI): Class I) inhibit C14-demethylase, which plays a role in
sterol production.
Sterols, such as ergosterol, are needed for membrane structure and function,
making them
essential for the development of functional cell walls. Therefore, exposure to
these fungicides
results in abnormal growth and eventually death of sensitive fungi. DMI
fungicides are divided
between several chemical classes: piperazines, pyridines, pyrimidines,
imidazoles, triazoles and
triazolinthiones. The piperazines include triforine. The pyridines include
buthiobate, pyrifenox,
pyrisoxazole and (aS)- [3-(4-chloro-2-fluoropheny1)-5-(2,4-difluoropheny1)-4-
isoxazoly1]-3-
pyridinemethanol. The pyrimidines include fenarimol, nuarimol and triarimol.
The imidazoles
include econazole, imazalil, oxpoconazole, pefurazoate, prochloraz and
triflumizole. The
triazoles include azaconazole, bitertanol, bromuconazole, cyproconazole,
difenoconazole,
diniconazole (including diniconazole-M), epoxiconazole, etaconazole,
fenbuconazole,
fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole,
ipconazole,
ipfentrifluconazole, mefentrifluconazole, metconazole, myclobutanil,
penconazole,
propiconazole, quinconazole, simeconazole, tebuconazole, tetraconazole,
triadimefon,
triadimenol, triticonazole, uniconazole, uniconazole-P, a-(1-
chlorocyclopropy1)-a- [242,2-
dichlorocyclopropyl)ethyl]- 1H-1,2,4-triazole-1-ethanol,
rel- 1- [ [(2R,35)-3 -(2-chloropheny1)-2 -
(2,4-difluoropheny1)-2-o xiranyl] methyl] - 1H-1,2,4 -triazole, re/-2-
[[(2R,35)-3 -(2 -chloropheny1)-
2-(2,4-difluoropheny1)-2-oxiranyl]methyl] -1,2-dihydro-3H-1,2,4-triazole-3-
thione and rel-1-
[[(2R,35)-3-(2-chloropheny1)-2-(2,4-difluoropheny1)-2-oxiranyllmethyl] -5-(2-
propen-1-ylthio)-
1H-1,2,4-triazole. The triazolinthiones include prothioconazole. Biochemical
investigations have
shown that all of the above mentioned fungicides are DMI fungicides as
described by K. H. Kuck
et al. in Modern Selective Fungicides - Properties, Applications and
Mechanisms of Action, H.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
28
Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.
"Phenylamide (PA) fungicides (b4)" (FRAC code 4) are specific inhibitors of
RNA
polymerase in Oomycete fungi. Sensitive fungi exposed to these fungicides show
a reduced
capacity to incorporate uridine into rRNA. Growth and development in sensitive
fungi is
prevented by exposure to this class of fungicide. Phenylamide fungicides
include acylalanine,
oxazolidinone and butyrolactone fungicides. The acylalanines include
benalaxyl, benalaxyl-M
(also known as kiralaxyl), furalaxyl, metalaxyl and metalaxyl-M (also known as
mefenoxam).
The oxazolidinones include oxadixyl. The butyrolactones include ofurace.
"Amine/morpholine fungicides (b5)" (FRAC code 5) (SBI: Class II) inhibit two
target sites
within the sterol biosynthetic pathway, A8 ¨>A7 isomerase and A14 reductase.
Sterols, such as
ergosterol, are needed for membrane structure and function, making them
essential for the
development of functional cell walls. Therefore, exposure to these fungicides
results in abnormal
growth and eventually death of sensitive fungi. Amine/morpholine fungicides
(also known as
non-DMI sterol biosynthesis inhibitors) include morpholine, piperidine and
spiroketal-amine
fungicides. The morpholines include aldimorph, dodemorph, fenpropimorph,
tridemorph and
trimorphamide. The piperidines include fenpropidin and piperalin. The
spiroketal-amines include
spiroxamine.
"Phospholipid biosynthesis inhibitor fungicides (b6)" (FRAC code 6) inhibit
growth of
fungi by affecting phospholipid biosynthesis. Phospholipid biosynthesis
fungicides include
phophorothiolate and dithiolane fungicides. The phosphorothiolates include
edifenphos,
iprobenfos and pyrazophos. The dithiolanes include isoprothiolane.
"Succinate dehydrogenase inhibitor (SDHI) fungicides (b7)" (FRAC code 7)
inhibit
complex II fungal respiration by disrupting a key enzyme in the Krebs Cycle
(TCA cycle) named
succinate dehydrogenase. Inhibiting respiration prevents the fungus from
making ATP, and thus
inhibits growth and reproduction.
SDHI fungicides include phenylbenzamide,
phenyloxoethylthiophene amide, pyridinylethylbenzamide, furan carboxamide,
oxathiin
carboxamide, thiazole carboxamide, pyrazole-4-carboxamide, N-cyclopropyl-N-
benzyl-pyrazole
carboxamide, N-methoxy-(phenyl-ethyl)-pyrazole carboxamide, pyridine
carboxamide and
pyrazine carboxamide fungicides. The phenylbenzamides include benodanil,
flutolanil and
mepronil. The phenyloxoethylthiophene amides include isofetamid.
The
pyridinylethylbenzamides include fluopyram. The furan carboxamides include
fenfuram. The
oxathiin carboxamides include carboxin and oxycarboxin. The thiazole
carboxamides include
thifluzamide. The pyrazole-4-carboxamides include benzovindiflupyr, bixafen,
flubeneteram
(provisional common name, Registry Number 1676101-39-5), fluindapyr,
fluxapyroxad,
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
29
furametpyr, inpyrfluxam, isopyrazam, penflufen, penthiopyrad, pyrapropoyne
(provisional
common name, Registry Number 1803108-03-3), sedaxane and N42-(2,4-
dichloropheny1)-2-
methoxy-1-methylethyl] -3 -(difluoromethyl)-1-methyl- 1H-pyrazole-4-c
arboxamide. The N-
cyclopropyl-N-benzyl-pyrazole carboxamides include isoflucypram. The N-methoxy-
(phenyl-
ethyl)-pyrazole carboxamides include pydiflumetofen. The pyridine carboxamides
include
boscalid. The pyrazine carboxamides include pyraziflumid.
"Hydroxy-(2-amino-)pyrimidine fungicides (b8)" (FRAC code 8) inhibit nucleic
acid
synthesis by interfering with adenosine deaminase. Examples include
bupirimate, dimethirimol
and ethirimol.
"Anilinopyrimidine (AP) fungicides (b9)" (FRAC code 9) are proposed to inhibit
biosynthesis of the amino acid methionine and to disrupt the secretion of
hydrolytic enzymes that
lyse plant cells during infection. Examples include cyprodinil, mepanipyrim
and pyrimethanil.
"N-Phenyl carbamate fungicides (b10)" (FRAC code 10) inhibit mitosis by
binding to f3-
tubulin and disrupting microtubule assembly. Inhibition of microtubule
assembly can disrupt cell
division, transport within the cell and cell structure. Examples include
diethofencarb.
"Quinone outside inhibitor (QoI) fungicides (b 1 1)" (FRAC code 11) inhibit
complex III
mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation
of ubiquinol is
blocked at the "quinone outside" (Qo) site of the cytochrome bci complex,
which is located in the
inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration
prevents normal
fungal growth and development. Quinone outside inhibitor fungicides include
methoxyacrylate,
methoxyacetamide, methoxycarbamate, oximinoacetate, oximinoacetamide and
dihydrodioxazine fungicides (collectively also known as strobilurin
fungicides), and
oxazolidinedione, imidazolinone and benzylcarbamate fungicides. The
methoxyacrylates include
azoxystrobin, coumoxystrobin, enoxastrobin (also known as enestroburin),
flufenoxystrobin,
picoxystrobin and pyraoxystrobin. The methoxyacetamides include mandestrobin.
The methoxy-
carbamates include pyraclostrobin, pyrametostrobin and triclopyricarb. The
oximinoacetates
include kresoxim-methyl and trifloxystrobin. The oximinoacetamides include
dimoxystrobin,
fenaminstrobin, metominostrobin and orysastrobin. The dihydrodioxazines
include fluoxastrobin.
The oxazolidinediones include famoxadone. The imidazolinones include
fenamidone. The
benzylcarbamates include pyribencarb.
"Phenylpyrrole (PP) fungicides (b12)" (FRAC code 12) inhibit a MAP/histidine
kinase
associated with osmotic signal transduction in fungi. Fenpiclonil and
fludioxonil are examples of
this fungicide class.
"Azanaphthalene fungicides (b13)" (FRAC code 13) are proposed to inhibit
signal
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
transduction by a mechanism which is as yet unknown. They have been shown to
interfere with
germination and/or appressorium formation in fungi that cause powdery mildew
diseases.
Azanaphthalene fungicides include aryloxyquinolines and quinazolinones. The
aryloxyquinolines include quinoxyfen. The quinazolinones include proquinazid.
5 "Cell peroxidation inhibitor fungicides (b14)" (FRAC code 14) are
proposed to inhibit lipid
peroxidation which affects membrane synthesis in fungi. Members of this class,
such as
etridiazole, may also affect other biological processes such as respiration
and melanin
biosynthesis. Cell peroxidation fungicides include aromatic hydrocarbon and
1,2,4-thiadiazole
fungicides. The aromatic hydrocarboncarbon fungicides include biphenyl,
chloroneb, dicloran,
10 quintozene, tecnazene and tolclofos-methyl. The 1,2,4-thiadiazoles
include etridiazole.
"Melanin biosynthesis inhibitor-reductase (MBI-R) fungicides (b15)" (FRAC code
16.1)
inhibit the naphthal reduction step in melanin biosynthesis. Melanin is
required for host plant
infection by some fungi.
Melanin biosynthesis inhibitor-reductase fungicides include
isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole fungicides. The
15 isobenzofuranones include fthalide. The pyrroloquinolinones include
pyroquilon. The
triazolobenzothiazoles include tricyclazole.
"Melanin biosynthesis inhibitor-dehydratase (MBI-D) fungicides (b16a)" (FRAC
code
16.2) inhibit scytalone dehydratase in melanin biosynthesis. Melanin is
required for host plant
infection by some fungi. Melanin biosynthesis inhibitor-dehydratase fungicides
include
20 cyclopropanecarboxamide, carboxamide and propionamide fungicides. The
cyclopropanecarboxamides include carpropamid. The carboxamides include
diclocymet. The
propionamides include fenoxanil.
"Melanin biosynthesis inhibitor-polyketide synthase (MBI-P) fungicides (b16b)"
(FRAC
code 16.3) inhibit polyketide synthase in melanin biosynthesis. Melanin is
required for host plant
25 infection by some fungi. Melanin biosynthesis inhibitor-polyketide
synthase fungicides include
trifluoroethylcarbamate fungicides. The trifluoroethylcarbamates include
tolprocarb.
"Keto reductase inhibitor (KRI) fungicides (b17)" (FRAC code 17) inhibit 3-
keto reductase
during C4-demethylation in sterol production. Keto reductase inhibitor
fungicides (also known
as Sterol Biosynthesis Inhibitors (SBI): Class III) include hydroxyanilides
and amino-
30 pyrazolinones. Hydroxyanilides include fenhexamid.
Amino-pyrazolinones include
fenpyrazamine. Quinofumelin (provisional common name, Registry Number 861647-
84-9) and
ipflufenoquin (provisional common name, Registry Number 1314008-27-9) are also
believed to
be keto reductase inhibitor fungicides.
"Squalene-epoxidase inhibitor fungicides (b18)" (FRAC code 18) (SBI: Class IV)
inhibit
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
31
squalene-epoxidase in the sterol biosynthesis pathway. Sterols such as
ergosterol are needed for
membrane structure and function, making them essential for the development of
functional cell
walls. Therefore exposure to these fungicides results in abnormal growth and
eventually death of
sensitive fungi. Squalene-epoxidase inhibitor fungicides include thiocarbamate
and allylamine
fungicides. The thiocarbamates include pyributicarb. The allylamines include
naftifine and
terbinafine.
"Polyoxin fungicides (b19)" (FRAC code 19) inhibit chitin synthase. Examples
include
polyoxin.
"Phenylurea fungicides (b20)" (FRAC code 20) are proposed to affect cell
division.
Examples include pencycuron.
"Quinone inside inhibitor (QiI) fungicides (b21)" (FRAC code 21) inhibit
complex III
mitochondrial respiration in fungi by affecting ubiquinone reductase.
Reduction of ubiquinone is
blocked at the "quinone inside" (Qi) site of the cytochrome bci complex, which
is located in the
inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration
prevents normal
fungal growth and development. Quinone inside inhibitor fungicides include
cyanoimidazole,
sulfamoyltriazole and picolinamide fungicides. The cyanoimidazoles include
cyazofamid. The
sulfamoyltriazoles include amisulbrom. The picolinamides include fenpicoxamid
(Registry
Number 517875-34-2).
"Benzamide and thiazole carboxamide fungicides (b22)" (FRAC code 22) inhibit
mitosis
by binding to 13-tubulin and disrupting microtubule assembly. Inhibition of
microtubule assembly
can disrupt cell division, transport within the cell and cell structure. The
benzamides include
toluamides such as zoxamide.
The thiazole carboxamides include ethylaminothiazole
carboxamides such as ethaboxam.
"Enopyranuronic acid antibiotic fungicides (b23)" (FRAC code 23) inhibit
growth of fungi
by affecting protein biosynthesis. Examples include blasticidin-S.
"Hexopyranosyl antibiotic fungicides (b24)" (FRAC code 24) inhibit growth of
fungi by
affecting protein biosynthesis. Examples include kasugamycin.
"Glucopyranosyl antibiotic: protein synthesis fungicides (b25)" (FRAC code 25)
inhibit
growth of fungi by affecting protein biosynthesis. Examples include
streptomycin.
"Glucopyranosyl antibiotic fungicides (b26)" (FRAC code U18, previously FRAC
code 26
reclassified to U18) are proposed to inhibit trehalase and inositol
biosynthesis. Examples include
validamycin.
"Cyanoacetamideoxime fungicides (b27)" (FRAC code 27) include cymoxanil.
"Carbamate fungicides (b28)" (FRAC code 28) are considered multi-site
inhibitors of fungal
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
32
growth. They are proposed to interfere with the synthesis of fatty acids in
cell membranes, which
then disrupts cell membrane permeability. Iodocarb, propamacarb and
prothiocarb are examples
of this fungicide class.
"Oxidative phosphorylation uncoupling fungicides (b29)" (FRAC code 29) inhibit
fungal
respiration by uncoupling oxidative phosphorylation. Inhibiting respiration
prevents normal
fungal growth and development. This class includes dinitrophenyl crotonates
such as binapacryl,
meptyldinocap and dinocap, and 2,6-dinitroanilines such as fluazinam.
"Organo tin fungicides (b30)" (FRAC code 30) inhibit adenosine triphosphate
(ATP)
synthase in oxidative phosphorylation pathway. Examples include fentin
acetate, fentin chloride
and fentin hydroxide.
"Carboxylic acid fungicides (b31)" (FRAC code 31) inhibit growth of fungi by
affecting
deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include
oxolinic acid.
"Heteroaromatic fungicides (b32)" (FRAC code 32) are proposed to affect
DNA/ribonucleic
acid (RNA) synthesis. Heteroaromatic fungicides include isoxazoles and
isothiazolones. The
isoxazoles include hymexazole and the isothiazolones include octhilinone.
"Phosphonate fungicides (b33)" (FRAC code P07, previously FRAC code 33
reclassified
to P07) include phosphorous acid and its various salts, including fosetyl-
aluminum.
"Phthalamic acid fungicides (b34)" (FRAC code 34) include teclofthalam.
"Benzotriazine fungicides (b35)" (FRAC code 35) include triazoxide.
"Benzene-sulfonamide fungicides (b36)" (FRAC code 36) include flusulfamide.
"Pyridazinone fungicides (b37)" (FRAC code 37) include diclomezine.
"Thiophene-carboxamide fungicides (b38)" (FRAC code 38) are proposed to affect
ATP
production. Examples include silthiofam.
"Complex I NADH oxidoreductase inhibitor fungicides (b39)" (FRAC code 39)
inhibit
electron transport in mitochondria and include pyrimidinamines such as
diflumetorim, pyrazole-
5-carboxamides such as tolfenpyrad, and quinazoline such as fenazaquin.
"Carboxylic acid amide (CAA) fungicides (b40)" (FRAC code 40) inhibit
cellulose synthase
which prevents growth and leads to death of the target fungus. Carboxylic acid
amide fungicides
include cinnamic acid amide, valinamide carbamate and mandelic acid amide
fungicides. The
cinnamic acid amides include dimethomorph, flumorph and pyrimorph. The
valinamide
carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb,
tolprocarb and
valifenalate (also known as valiphenal). The mandelic acid amides include
mandipropamid, N-
[2- [4- [ [3 -(4-chloropheny1)-2-propyn-1 -yl] oxyl -3 -methoxyphenyll ethyl] -
3 -methy1-2-
Rmethylsulfonyl)aminol butanamide and N- [2- [4- [ [3 -(4-chloropheny1)-2-
propyn-1-yl] oxy I -3-
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
33
methoxyphenyl] ethyl] -3 -methyl-2- [(ethylsulfonyl)amino]butanamide.
"Tetracycline antibiotic fungicides (b41)" (FRAC code 41) inhibit growth of
fungi by
affecting protein synthesis. Examples include oxytetracycline.
"Thiocarbamate fungicides (b42)" (FRAC code M12, previously FRAC code 42
reclassified
to M12) include methasulfocarb.
"Benzamide fungicides (b43)" (FRAC code 43) inhibit growth of fungi by
delocalization of
spectrin-like proteins. Examples include pyridinylmethyl benzamides such as
fluopicolide and
fluopimomide.
"Microbial fungicides (b44)" (FRAC code BM02, previously FRAC code 44
reclassified to
BM02) disrupt fungal pathogen cell membranes. Microbial fungicides include
Bacillus species
such as Bacillus arnyloliquefaciens strains AP-136, AP-188, AP-218, AP-219, AP-
295, QST713,
FZB24, F727, MB1600, D747, TJ100 (also called strain 1 BE; known from
EP2962568), and the
fungicidal lipopeptides which they produce.
"Quinone outside inhibitor, stigmatellin binding (QoSI) fungicides (b45)"
(FRAC code 45)
inhibit complex III mitochondrial respiration in fungi by affecting ubiquinone
reductase at the
"quinone outside" (Qo) site, stigmatellin binding sub-site, of the cytochrome
bc 1 complex.
Inhibiting mitochondrial respiration prevents normal fungal growth and
development. QoSI
fungicides include triazolopyrimidylamines such as ametoctradin.
"Plant extract fungicides (b46)" (FRAC code 46) cause cell membrane
disruption. Plant
extract fungicides include terpene hydrocarbons, terpene alcohols and terpen
phenols such as the
extract from Melaleuca altemifolia (tea tree) and plant oils (mixtures) such
as eugenol, geraniol
and thymol.
"Cyanoacrylate fungicides (b47)" (FRAC code 47) bind to the myosin motor
domain and
effect motor activity and actin assembly. Cyanoacrylates include fungicides
such as phenamacril.
"Polyene fungicides (b48)" (FRAC code 48) cause disruption of the fungal cell
membrane
by binding to ergosterol, the main sterol in the membrane. Examples include
natamycin
(pimaricin).
"Oxysterol binding protein inhibitor (OSBPI) Fungicides (b49)" (FRAC code 49)
bind to
the oxysterol-binding protein in oomycetes causing inhibition of zoospore
release, zoospore
motility and sporangia germination. Oxy sterol binding fungicides include
piperdinylthiazoleisoxazolines such as oxathiapiprolin and fluoxapiprolin.
"Aryl-phenyl-ketone fungicides (b50)" (FRAC code 50, previously FRAC code U8
reclassified to 50) inhibit the growth of mycelium in fungi. Aryl-phenyl
ketone fungicides include
benzophenones such as metrafenone, and benzoylpyridines such as pyriofenone.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
34
"Host plant defense induction fungicides (b51)" induce host plant defense
mechanisms.
Host plant defense induction fungicides include benzothiadiazole (FRAC code
P01),
benzisothiazole (FRAC code P02), thiadiazole carboxamide (FRAC code P03),
polysaccharide
(FRAC code PO4), plant extract (FRAC code P05), microbial (FRAC code P06) and
phosphonate
fungicides (FRAC code P07, see (b33) above). The benzothiadiazoles include
acibenzolar-S-
methyl. The benzisothiazoles include probenazole. The thiadiazole carboxamides
include tiadinil
and isotianil. The polysaccharides include laminarin. The plant extracts
include extract from
Reynoutria sachalinensis (giant knotweed). The microbials include Bacillus
rnycoides isolate J
and cell walls of Saccharornyces cerevisiae strain LAS 117.
"Multi-site activity fungicides (b52)" inhibit fungal growth through multiple
sites of action
and have contact/preventive activity. Multi-site activity fungicides include
copper fungicides
(FRAC code M01), sulfur fungicides (FRAC code M02), dithiocarbamate fungicides
(FRAC code
M03), phthalimide fungicides (FRAC code M04), chloronitrile fungicides (FRAC
code M05),
sulfamide fungicides (FRAC code M06), multi-site contact guanidine fungicides
(FRAC code
M07), triazine fungicides (FRAC code M08), quinone fungicides (FRAC code M09),
quinoxaline
fungicides (FRAC code M10), maleimide fungicides (FRAC code M11) and
thiocarbamate
(FRAC code M12, see (b42) above) fungicides. Copper fungicides are inorganic
compounds
containing copper, typically in the copper(II) oxidation state; examples
include copper
oxychloride, copper sulfate and copper hydroxide (e.g., including compositions
such as Bordeaux
mixture (tribasic copper sulfate). Sulfur fungicides are inorganic chemicals
containing rings or
chains of sulfur atoms; examples include elemental sulfur. Dithiocarbamate
fungicides contain a
dithiocarbamate molecular moiety; examples include ferbam, mancozeb, maneb,
metiram,
propineb, thiram, zinc thiazole, zineb and ziram. Phthalimide fungicides
contain a phthalimide
molecular moiety; examples include folpet, captan and captafol. Chloronitrile
fungicides contain
an aromatic ring substituted with chloro and cyano; examples include
chlorothalonil. Sulfamide
fungicides include dichlofluanid and tolyfluanid. Multi-site contact guanidine
fungicides include,
guazatine, iminoctadine albesilate and iminoctadine triacetate. Triazine
fungicides include
anilazine. Quinone fungicides include dithianon.
Quinoxaline fungicides include
quinomethionate (also known as chinomethionate). Maleimide fungicides include
fluoroimide.
"Biologicals with multiple modes of action (b53)" include agents from
biological origins
showing multiple mechanisms of action without evidence of a dominating mode of
action. This
class of fungicides includes polypeptide (lectin), phenol, sesquiterpene,
tritepenoid and coumarin
fungicides (FRAC code BM01) such as extract from the cotyledons of lupine
plantlets. This class
also includes momicrobial fungicides (FRAC code BM02, see (b44) above).
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
"Fungicides other than fungicides of component (a) and components (b 1)
through (b53);
(b54)"; include certain fungicides whose mode of action may be unknown. These
include: (b54.1)
"phenyl-acetamide fungicides" (FRAC code U06), (b54.2) "guanidine fungicides"
(FRAC code
U12), (b54.3) "thiazolidine fungicides" (FRAC code U13), (b54.4) "pyrimidinone-
hydrazone
5 fungicides" (FRAC code U14), (b54.5) "4-quinolylacetate fungicides" (FRAC
code U16), (54.6)
"tetrazolyloxime fungicides" (FRAC code U17) and "glucopyranosyl antibiotic
fungicides"
(FRAC code U18, see (b26) above). The phenyl-acetamides include cyflufenamid.
The
guanidines include dodine. The thiazolidines include flutianil. The
pyrimidinonehydrazones
include ferimzone. The 4-quinolylacetates include tebufloquin. The
tetrazolyloximes include
10 picarbutrazox.
The (b54) class also includes bethoxazin, dichlobentiazox (provisional common
name,
Registry Number 957144-77-3), dipymetitrone (provisional common name, Registry
Number
16114-35-5), flometoquin, neo-asozin (ferric methanearsonate), pyrrolnitrin,
tolnifanide (Registry
Number 304911-98-6), /V- [4- [4-chloro-3-(trifluoromethyl)phenoxy] -2,5-
dimethylphenyll -N-
15 ethyl-N-methylmethanimidamide, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-
pyrimidinamine and
4-fluorophenyl N-[1-[[[1-(4-cyanophenyl)ethyl] sulfonyll methyl] propyll
carbamate.
Additional "Fungicides other than fungicides of classes (1) through (54)"
whose mode of
action may be unknown, or may not yet be classified include a fungicidal
compound selected from
components (b54.7) through (b54.13), as described below.
20
Component (54.7) relates to (1S)-2,2-bis(4-fluoropheny1)-1-methylethyl N-[ [3 -
(acetyloxy)-
4-methoxy-2-pyridinyl[carbonyll-L-alaninate (provisional common name
florylpicoxamid,
Registry Number 1961312-55-9) which is believed to be a Quinone inside
inhibitor (QiI)
fungicide (FRAC code 21) inhibiting the Complex III mitochondrial respiration
in fungi.
Component (54.8) relates to 1- [2- [[[1-(4-chloropheny1)-1H-pyrazol-3-yl]oxyl
methyl] -3-
25 methylphenyll -1,4-dihydro-4-
methyl-5H-tetrazol-5-one (provisional common name
metyltetraprole, Registry Number 1472649-01-6), which is believed to be a
quinone outside
inhibitor (QoI) fungicide (FRAC code 45) inhibiting the Complex III
mitochondrial respiration in
fungi, and is effective against QoI resistant strains.
Component (54.9) relates to 3-chloro-4-(2,6-difluoropheny1)-6-methy1-5-
phenylpyridazine
30 (provisional common name pyridachlometyl, Registry Number 1358061-55-8),
which is believed
to be promoter tubulin polymerization, resulting antifungal activity against
fungal species
belonging to the phyla Ascomycota and Basidiomycota.
Component (54.10) relates to (4-phenoxyphenyl)methyl 2-amino-6-methyl-pyridine-
3-
carboxylate (provisional common name aminopyrifen, Registry Number 1531626-08-
0) which is
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
36
believed to inhibit GWT-1 protein in glycosylphosphatidylinositol-anchor
biosynthesis in
Neurospora cras s a.
Component (b54.11) relates a compound of Formula b54.11
H3c
Rbl
OyN 441, b2
H3C R
0
b54.11
Rb3
wherein
Rbl and Rb3 are each independently halogen; and
Rb2 is H, halogen, C1-C3 alkyl, C1-C3 haloalkyl or C3-C6 cycloalkyl.
Examples of compounds of Formula b54.11 include (b54. ha) methyl N-[[5-[1-(2,6-
difluoro-4-
formylpheny1)-1H-pyrazol-3-yl] -2-methylphenyl] methyl] c arb amate, (b 54
.11b) methyl N-[[5-[1-
(4-cyclopropy1-2,6-dichloropheny1)-1H-pyrazol-3 -yl] -2-methylphenyl] methyl]
c arb amate,
(b54 .11c)
methyl N-[ [5- [1- (4-chloro-2,6-diflu oropheny1)-1H-pyrazol-3 -yl] -2-
methylphenyl] -
methyl]carbamate, (b54. lid) methyl N-[ [5- [1-(4-cyclopropy1-2,6-
difluoropheny1)-1H-pyrazol-3-
yl] -2-methylphenyl] methyl] c arb amate, (b54 .11e)
methyl N-[ [5- [1- [2,6-difluoro-4-(1-
methylethyl)phenyl] -1H-pyrazol-3-yl] -2-methylphenyl] methyl] c arb amate and
(b54 .11f) methyl
N- [[5- [1- [2,6-difluoro -4- (trifluoromethyl)phenyl] - 1H-pyrazol-3 -yl] -2-
methylphenyl] methyl]
carbamate. Compounds of Formula b54.11, their use as fungicides and methods of
preparation
are generally known; see, for example, PCT Patent Publications WO 2008/124092,
WO 2014/066120 and WO 2020/097012.
Component (b54.12) relates a compound of Formula b54.12
Rb5
Rm [001
b54.12
wherein
Rb4 is
Rb6
\N
or ;
Rb6 0
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
37
Rb6 is C2-C4 alkoxycarbonyl or C2-C4 haloalkylaminocarbonyl;
L is CH2 or CH20, wherein the atom to the right is connected to the phenyl
ring in Formula
b54.12; and
Rb5 is
(.)
)----CF3
Examples of compounds of Formula b54.12 include (b54.12a) N-(2,2,2-
trifluoroethyl)-24[445-
(trifluoromethyl)-1,2,4-oxadiazol-3-yl[phenyl[methyll-4-oxazolecarboxamide and
(b54.12b)
ethyl 1- [[4- [5- (trifluoromethyl)-1,2,4-oxadiazol-3 -yl] phenoxyl methyl] -
1H-pyrazole-4-
carboxylate. Compounds of Formula b54.11, their use as fungicides and methods
of preparation
are generally known; see, for example, PCT Patent Publication WO 2020/056090.
Component (b54.13) relates a compound of Formula b54.13
Rb8
411 Rb7
Rb10 D b9
bl 1 CH3
R \
N
C
NO2 H3
b54.13
wherein
Rb7, Rb8 and Rb9 are each independently H, halogen or cyano; and
Rb10 and Rbll are each independently H, halogen, C1-C3 alkyl or C1-C3 methoxy.
Examples of compounds of Formula b54.13 include (b54.13a) 4-(2-chloro-4-
fluoropheny1)-N-(2-
fluoro-4-methy1-6-nitropheny1)- 1,3 -dimethy1-1H-pyrazol-5- amine, (b54.13b) 4-
(2 -chloro-4 -
fluoropheny1)-N- (2-fluoro-6-nitropheny1)-1,3 -dimethy1-1H-pyrazol-5- amine,
(b54 .13 c ) 3 ,5-
difluoro-4- [5- [(4-methoxy-2-nitrophenyl)amino] -1,3 -dimethyl- 1H-pyrazol-4-
yll -benzonitrile
and (b54.13d) N-(2-chloro-4-fluoro-6-nitropheny1)-4-(2-chloro-4-fluoropheny1)-
1,3-dimethyl-
1H-pyrazol-5-amine. Compounds of Formula b54.11, their use as fungicides and
methods of
preparation are generally known; see, for example, PCT Patent Publication WO
2020051402.
Embodiments of the present invention as described in the Summary of the
Invention include
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
38
those described below. In the following Embodiments, Formula 1 includes
stereoisomers,
N-oxides, and salts thereof, and reference to "a compound of Formula 1"
includes the definitions
of substituents specified in the Summary of the Invention unless further
defined in the
Embodiments.
Embodiment 1. The composition comprising components (a) and (b) described in
the
Summary of the Invention wherein in Formula 1, T is T-1.
Embodiment 2. The composition comprising components (a) and (b) described in
the
Summary of the Invention wherein in Formula 1, T is T-2.
Embodiment 3. The composition comprising components (a) and (b) described in
the
Summary of the Invention wherein in Formula 1, T is T-3.
Embodiment 3a. The composition comprising components (a) and (b) described in
the
Summary of the Invention wherein in Formula 1, T is T-2 or T-3.
Embodiment 4. The composition comprising components (a) and (b) described in
the
Summary of the Invention wherein in Formula 1, R1 is CF3.
Embodiment 5. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 4 wherein in
Formula 1, W is 0 or S.
Embodiment 6. The composition of Embodiment 5 wherein W is 0.
Embodiment 7. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 4 wherein in
Formula 1, W is NR3.
Embodiment 8. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 7 wherein in
Formula 1, R3 is H, cyano, C(=0)0H, C1-C2 alkyl, C2-C3 alkylcarbonyl, C2-C3
haloalkylcarbonyl, 0R3a or NR3bR3c.
Embodiment 9. The composition of Embodiment 8 wherein R3 is H, cyano, C1-C2
alkyl or
0R3a.
Embodiment 10. The composition of Embodiment 9 wherein R3 is H, cyano or 0R3a.
Embodiment 11. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 10 wherein in
Formula 1, R3a is H, C1-C2 alkyl, C2-C3 alkylcarbonyl or C2-C3
haloalkylcarbonyl.
Embodiment 12. The composition of Embodiment 11 wherein R3a is H.
Embodiment 13. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 12 wherein in
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
39
Formula 1, when R3b is separate (i.e. not taken together with R3C to form a
ring),
then R3b is H, C1-C3 alkyl, C2-C3 alkylcarbonyl or C2-C3 haloalkylcarbonyl.
Embodiment 14. The composition of Embodiment 13 wherein R3b is H or methyl.
Embodiment 15. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 14 wherein in
Formula 1, when R3C is separate (i.e. not taken together with R3b to form a
ring),
then R3C is H or C1-C2 alkyl.
Embodiment 16. The composition of Embodiment 15 wherein R3C is H or methyl.
Embodiment 17. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 16 wherein in
Formula 1, X is 0 or NR5a.
Embodiment 18. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 16 wherein in
Formula 1, X is 0, S, NH or NOH.
Embodiment 19. The composition of Embodiment 18 wherein X is 0 or NOH.
Embodiment 20. The composition of Embodiment 20 wherein X is 0.
Embodiment 21. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 20 wherein in
Formula 1, Y is 0 or NR5b.
Embodiment 22. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 20 wherein in
Formula 1, Y is 0, S, NH or NOH.
Embodiment 23. The composition of Embodiment 22 wherein Y is 0 or NOH.
Embodiment 24. The composition of Embodiment 23 wherein Y is 0.
Embodiment 25. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 24 wherein in
Formula 1, R5a and R5b are each independently H, hydroxy or C1-C2 alkyl.
Embodiment 26. The composition of Embodiment 25 wherein R5a and R5b are each
independently H, hydroxy or methyl.
Embodiment 27. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 26 wherein in
Formula 1, when R2a and R2b are separate (i.e. not taken together to form a
ring),
then R2a and R2b are each independently H, C1-C3 alkyl, C2-C3 alkenyl,
(CR4aR4b) _OH, (CR4aR4b) _Cl or (CR4aR4b) _Br
P P P =
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
Embodiment 27a. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 26 wherein in
Formula 1, when R2a and R2b are separate (i.e. not taken together to form a
ring),
then R2a and R2b are each independently H, C1-C3 alkyl, C3-C15 trialkylsilyl
or
5 C3-C15 halotrialkylsilyl.
Embodiment 27b. The composition of Embodiment 27a wherein R2a and R2b are each
independently H, methyl, trimethylsilyl or halotrimethylsilyl.
Embodiment 27c. The composition of Embodiment 27b wherein R2a and R2b are each
independently H, methyl, trimethylsilyl or trifluoromethylsilyl
10 Embodiment 27d. The composition of Embodiment 27c wherein R2a and R2b
are each
independently H, methy or trimethylsilyl.
Embodiment 27e. The composition of Embodiment 27d wherein R2a is H and R2b is
trimethylsilyl.
Embodiment 27f. The composition of Embodiment 27d wherein R2a is methyl and
R2b is
15 trimethylsilyl.
Embodiment 28. The composition of Embodiment 27 wherein R2a and R2b are each
independently H, C1-C3 alkyl, (CR4aR4b)p_Cl or (CR4aR4b)p_Br.
Embodiment 29. The composition of Embodiment 28 wherein R2a and R2b are each
independently H, methyl, (CR4aR4b)p_Cl or (CR4aR4b)p_Br.
20 Embodiment 30. The composition of Embodiment 28 wherein R2a and R2b are
each
independently H or C1-C3 alkyl.
Embodiment 31. The composition of Embodiment 30 wherein R2a and R2b are each
independently H or C1-C2 alkyl.
Embodiment 32. The composition of Embodiment 31 wherein R2a and R2b are each
25 independently H or methyl.
Embodiment 33. The composition of Embodiment 32 wherein R2a and R2b are each
H.
Embodiment 34. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 33 wherein in
Formula 1, when R2a and R2b are separate (i.e. not taken together to form a
ring),
30 then one of R2a and R2b is (cR4aR4b)p_OH, (CR4aR4b)p_SH,
(CR4aR4b)p_Cl or
(cR4aR4b)p-Br, and the other is H.
Embodiment 35. The composition of Embodiment 34 wherein one of R2a and R2b is
(cR4aR4b)p_Cl or (CR4aR4b)p_Br, and the other is H.
Embodiment 36. The composition comprising components (a) and (b) described in
the
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
41
Summary of the Invention or any one of Embodiments 1 through 35 wherein in
Formula 1, R2a and R2b are each independently H, methyl, (CR4aR4b) _pH,
P
(cR4aR4b)p_Cl or (CR4aR4b)p_Br; or R2a and R2b are taken together with the
atoms
X and Y to which they are attached to form a 5- to 6-membered saturated ring
containing ring members, in addition to the atoms X and Y, selected from
carbon
atoms, wherein up to 2 carbon atom ring members are independently selected
from
C(=0) and C(=S), the ring optionally substituted with up to 2 substituents
independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-
C2
alkoxy and C1-C2 haloalkoxy on carbon atom ring members.
Embodiment 37. The composition of Embodiment 36 wherein R2a and R2b are each
independently H or methyl; or R2a and R2b are taken together with the atoms X
and
Y to which they are attached to form a 5- to 6-membered saturated ring
containing
ring members, in addition to the atoms X and Y, selected from carbon atoms,
wherein up to 1 carbon atom ring member is selected from C(=0), the ring
optionally substituted with up to 2 substituents independently selected from
halogen,
cyano, methyl, halomethyl, methoxy and halomethoxy on carbon atom ring
members.
Embodiment 38. The composition of Embodiment 37 wherein R2a and R2b are each
independently H or methyl; or R2a and R2b are taken together with the atoms X
and
Y to which they are attached to form a 5-membered saturated ring containing
ring
members, in addition to the atoms X and Y, selected from carbon atoms, the
ring
optionally substituted with up to 1 substituent selected from halogen, cyano
and
methyl on carbon atom ring members.
Embodiment 39. The composition of Embodiment 38 wherein R2a and R2b are each
H; or
R2a and R2b are taken together with the atoms X and Y to which they are
attached to
form a 5-membered saturated ring containing ring members, in addition to the
atoms
X and Y, selected from carbon atoms, the ring optionally substituted with up
to 1
substituent selected methyl on a carbon atom ring member.
Embodiment 40. The composition of Embodiment 39 wherein R2a and R2b are each
H; or
R2a and R2b are taken together with the atoms X and Y to which they are
attached to
form a 5-membered saturated ring containing ring members, in addition to the
atoms
X and Y, selected from carbon atoms.
Embodiment 41. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 40 wherein in
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
42
Formula 1, when R2a and R2b are taken together to form a ring (i.e. not
separate),
then R2a and R2b are taken together with the atoms X and Y to which they are
attached to form a 5- to 6-membered saturated ring containing ring members, in
addition to the atoms X and Y, selected from carbon atoms, wherein up to 1
carbon
atom ring member is selected from C(=0), the ring optionally substituted with
up to
2 substituents independently selected from halogen, cyano, methyl, halomethyl,
methoxy and halomethoxy on carbon atom ring members.
Embodiment 42. The composition of Embodiment 41 wherein R2a and R2b are taken
together with the atoms X and Y to which they are attached to form a 5-
membered
saturated ring containing ring members, in addition to the atoms X and Y,
selected
from carbon atoms, the ring optionally substituted with up to 2 substituents
independently selected from halogen, cyano, methyl, halomethyl and methoxy on
carbon atom ring members.
Embodiment 43. The composition of Embodiment 42 wherein R2a and R2b are taken
together with the atoms X and Y to which they are attached to form a 5-
membered
saturated ring containing ring members, in addition to the atoms X and Y,
selected
from carbon atoms, the ring optionally substituted with up to 1 substituent
selected
from halogen, methyl and halomethyl on a carbon atom ring member.
Embodiment 44. The composition of Embodiment 43 wherein R2a and R2b are taken
together with the atoms X and Y to which they are attached to form a 5-
membered
saturated ring containing ring members, in addition to the atoms X and Y,
selected
from carbon atoms.
Embodiment 45. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 44 wherein in
Formula 1, R2c is C1-C3 alkyl, C1-C3 haloalkyl, C2-C3 alkenyl, C2-C3
haloalkenyl,
C2-C3 alkynyl or C2-C3 haloalkynyl, each optionally substituted with up 1
substituent selected from cyano, hydroxy, SCI\T and C1-C2 alkoxy.
Embodiment 46. The composition of Embodiment 45 wherein R2c is C1-C2 alkyl, C1-
C2
haloalkyl, C2-C3 alkenyl, C2-C3 haloalkenyl, C2-C3 alkynyl or C2-C3
haloalkynyl,
each optionally substituted with up 1 substituent selected from cyano and
methoxy.
Embodiment 46a. The composition of Embodiment 46 wherein R2c is C1-C2 alkyl,
C1-C2
haloalkyl, C2-C3 alkenyl, C2-C3 haloalkenyl or C2-C3 alkynyl.
Embodiment 47. The composition of Embodiment 46a wherein R2c is C1-C2 alkyl,
C2-C3
alkenyl or C2-C3 alkynyl.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
43
Embodiment 48. The composition of Embodiment 47 wherein R2c is methyl or
ethyl.
Embodiment 48a. The composition of Embodiment 48 wherein R2c is ethyl.
Embodiment 49. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 48a wherein in
Formula 1, R2d is H, cyano, halogen or C1-C2 alkyl.
Embodiment 49a. The composition of Embodiment 49 wherein R2d is H, cyano, Cl,
F or
methyl.
Embodiment 50. The composition of Embodiment 49a wherein R2d is H or methyl.
Embodiment 51. The composition of Embodiment 50 wherein R2d is H.
Embodiment 52. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 51 wherein in
Formula 1, each R4a and R4b is independently H or C1-C2 alkyl.
Embodiment 53. The composition of Embodiment 52 wherein each R4a and R4b is
independently H or methyl.
Embodiment 54. The composition of Embodiment 53 wherein each R4a and R4b is H.
Embodiment 55. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 54 wherein in
Formula 1, p is 2.
Embodiment 56. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 54 wherein in
Formula 1, p is 3.
Embodiment 57. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 56 wherein in
Formula 1, wherein A1 is cR6cR6d, 0 or S.
Embodiment 58. The composition of Embodiment 57 wherein A1 is cR6cR6d or a
Embodiment 59. The composition of Embodiment 58 wherein A1 is cR6cR6d.
Embodiment 60. The composition of Embodiment 58 wherein A1 is 0.
Embodiment 61. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 60 wherein in
Formula 1, A1 is CH2, NH, 0 or S.
Embodiment 62. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 61 wherein in
Formula 1, A1 is N(R7a).
Embodiment 63. The composition comprising components (a) and (b) described in
the
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
44
Summary of the Invention or any one of Embodiments 1 through 63 wherein in
Formula 1, A2 is a direct bond, CR6eR6f, 0 or S.
Embodiment 64. The composition of Embodiment 63 wherein A2 is a direct bond,
CR6eR6f
or O.
Embodiment 65. The composition of Embodiment 64 wherein A2 is a direct bond or
0.
Embodiment 66. The composition of Embodiment 65 wherein A2 is a direct bond.
Embodiment 67. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 62 wherein in
Formula 1, A2 is a direct bond, CH2, NH, 0 or S.
Embodiment 67a. The composition of Embodiment 67 wherein A2 is a direct bond,
CH2 or
0.
Embodiment 68. The composition of Embodiment 67a wherein A2 is a direct bond
or 0.
Embodiment 69. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 62 wherein in
Formula 1, A2 is N(R7b).
Embodiment 70. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 69 wherein in
Formula 1, when A is Al_A2_cR6aR6b, then A l_A2_cR6aR6b is selected from
0CH2, OCH(Me), CH(OH)CH2, CH2CH2, SCH2, 0CF2 and CH2OCH2.
Embodiment 71. The composition of Embodiment 70 wherein Al_A2_cR6aR6b is
selected
from 0CH2, OCH(Me) and CH2CH2.
Embodiment 72. The composition of Embodiment 71 wherein Al_A2_cR6aR6b is
selected
from 0CH2 and CH2CH2.
Embodiment 73. The composition of Embodiment 72 wherein Ai_A2_cR6aR6b is 0cH2.
Embodiment 74. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 74 wherein in
Formula 1, when A is A1-A2, then A1-A2 is selected from 0, CH2, 0CH2 and
CH20.
Embodiment 75. The composition of Embodiment 74 wherein A1-A2 is selected from
0,
CH2 and CH20.
Embodiment 76. The composition of Embodiment 75 wherein A1-A2 is selected from
0
and CH2.
Embodiment 77. The composition of Embodiment 76 wherein A1-A2 is 0.
Embodiment 78. The composition comprising components (a) and (b) described in
the
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
Summary of the Invention or any one of Embodiments 1 through 77 wherein in
Formula 1, R6a, R6b, R6c, R6d, R6e and R6f are each independently H, cyano,
hydroxy, Br, Cl, F or methyl.
Embodiment 79. The composition of Embodiment 78 wherein R6a, R6b, R6c, R6d,
R6e and
5 R6f are each independently H, cyano hydroxy or methyl.
Embodiment 80. The composition of Embodiment 79 wherein R6a, R6b, R6c, R6d,
R6e and
R6f are each independently H or methyl.
Embodiment 81. The composition of Embodiment 80 wherein R6a, R6b, R6c, R6d,
R6e and
R6f are each H.
10 Embodiment 82. The composition comprising components (a) and (b)
described in the
Summary of the Invention or any one of Embodiments 1 through 81 wherein in
Formula 1, R7a and 1271) are each independently H, C1-C2 alkyl or C2-C3
alkylcarbonyl.
Embodiment 83. The composition of Embodiment 82 wherein R7a and R7b are each
15 independently H or C1-C2 alkyl.
Embodiment 84. The composition of Embodiment 83 wherein R7a and R7b are each
H.
Embodiment 85. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 84 wherein in
Formula 1, when T is T-1 or T-2, then A is A1-A2-CH2.
20 Embodiment 86. The composition comprising components (a) and (b)
described in the
Summary of the Invention or any one of Embodiments 1 through 85 wherein in
Formula 1, when T is T-1 or T-2, then A is OCH2, SCH2, NHCH2, CH2CH2,
OCH2CH2, SCH2CH2, NHCH2CH2, CH2OCH2, CH2SCH2 or CH2NHCH2.
Embodiment 87. The composition of Embodiment 86 wherein when T is T-1 or T-2,
then
25 A is OCH2, SCH2, CH2CH2, OCH2CH2, SCH2CH2, CH2OCH2 or CH2SCH2.
Embodiment 88. The composition of Embodiment 87 wherein when T is T-1 or T-2,
then
A is OCH2 or CH2CH2.
Embodiment 89. The composition of Embodiment 88 wherein when T is T-1 or T-2,
then
A is OCH2.
30 Embodiment 90. The composition comprising components (a) and (b)
described in the
Summary of the Invention or any one of Embodiments 1 through 89 wherein in
Formula 1, when T is T-3, then A is 0, 0CH2, SCH2, NHCH2, CH2, CH2CH2,
CH20, CH2S or CH2NH.
Embodiment 91. The composition of Embodiment 82 wherein when T is T-3, then A
is 0,
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
46
CH2 or OCH2.
Embodiment 92. The composition of Embodiment 91 wherein when T is T-3, then A
is 0
or CH2.
Embodiment 93. The composition of Embodiment 92 wherein when T is T-3, then A
is 0.
Embodiment 94. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 93 wherein in
Formula 1, J is J-1 through J-3, J-6 through J-10 or J-14.
Embodiment 95. The composition of Embodiment 94 wherein J is J-1, J-2, J-3, J-
6 or J-14.
Embodiment 96. The composition of Embodiment 95 wherein J is J-1, J-6 or J-14.
Embodiment 97. The composition of Embodiment 96 wherein J is J-1 or J-6.
Embodiment 97a. The composition of Embodiment 96 wherein J is J-14.
Embodiment 98. The composition of Embodiment 97 wherein J is J-1.
Embodiment 99. The composition of Embodiment 97 wherein J is J-6.
Embodiment 100. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 99 wherein in
Formula 1, each R8 is independently F, Cl or methyl.
Embodiment 100a. The composition of Embodiment 100 wherein each R8 is
independently
F or Cl.
Embodiment 101. The composition of Embodiment 100 wherein each R8 is
independently
F or methyl.
Embodiment 101a. The composition of Embodiment 101 wherein each R8 is F.
Embodiment 102. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 101a wherein in
Formula 1, q is 0 or 1.
Embodiment 102a. The composition comprising components (a) and (b) described
in the
Summary of the Invention or any one of Embodiments 1 through 101a wherein in
Formula 1, q is 3 or 4.
Embodiment 102b. The composition of Embodiment 102a wherein in Formula 1, q is
4.
Embodiment 103. The composition of Embodiment 102 wherein q is 0.
Embodiment 103a. The composition of Embodiment 102 wherein q is 1.
Embodiment 104. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 103a wherein in
Formula 1, each R9a and R9b is independently H, halogen, C1-C3 alkyl, C1-C3
haloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
47
Embodiment 105. The composition of Embodiment 104 wherein each R9a and R9b is
independently H, halogen, C1-C2 alkyl or C1-C2 haloalkyl.
Embodiment 106. The composition of Embodiment 105 wherein each R9a and R9b is
independently H, halogen or methyl.
Embodiment 107. The composition of Embodiment 106 wherein each R9a and R9b is
independently H or methyl.
Embodiment 108. The composition of Embodiment 107 wherein each R9a and R9b is
H.
Embodiment 109. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 108 wherein in
Formula 1, n is 0, 1 or 2.
Embodiment 109a. The composition of Embodiment 109 wherein n is 1 or 2.
Embodiment 110. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 109a wherein in
Formula 1, n is 0 or 1.
Embodiment 111. The composition of Embodiments 109, 109a or 110 wherein n is
1.
Embodiment 112. The composition of Embodiments 109 or 110 wherein n is 0.
Embodiment 113. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 112 wherein in
Formula 1, L is a direct bond, CH2, CH(Me) or CH2CH2.
Embodiment 113a. The composition of Embodiment 113 wherein L is a direct bond,
CH2
or CH2CH2.
Embodiment 114. The composition of Embodiment 113a wherein L is a direct bond
or
CH2.
Embodiment 115. The composition of Embodiment 114 wherein L is CH2.
Embodiment 115a. The composition of Embodiment 114 wherein L is a direct bond.
Embodiment 116. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 115a wherein in
Formula 1, E is El.
Embodiment 116a. The composition comprising components (a) and (b) described
in the
Summary of the Invention or any one of Embodiments 1 through 116 wherein in
Formula 1, when L is a direct bond, then E is El.
Embodiment 117. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 116a wherein in
Formula 1, E1 is cyano, nitro, C(=0)H, C(=0)0H or SCI\T; or C1-C6 alkoxy, C2-
C6
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
48
alkenyloxy, C1-C6 alkylsulfonyl, C2-C6 alkenylsulfonyl, C2-C6 alkynylsulfonyl,
C1-C6 alkylsulfonylamino, C2-C6 alkenylsulfonylamino, C2-C6
alkynylsulfonylamino, C1-C6 alkylaminosulfonyl, C2-C6 dialkylaminosulfonyl,
C2-C6 alkenylaminosulfonyl, C2-C6 alkylcarbonyl, C2-C6 alkylaminocarbonyl,
C3-C6 alkenylaminocarbonyl, C3-C6 alkynylaminocarbonyl, C2-C6 alkoxycarbonyl,
C3-C6 alkenyloxycarbonyl, C3-C6 alkynyloxycarbonyl or C2-C6
alkoxycarbonylamino, wherein each carbon atom is optionally substituted with
up to
1 substituent selected from R10a and up to 3 substituents independently
selected
from R1M.
Embodiment 118. The composition of Embodiment 117 wherein El is cyano, nitro,
C(=0)H, C(=0)0H or SCI\T; or C1-C6 alkoxy, C2-C6 alkenyloxy, C1-C6
alkylsulfonyl, C1-C6 alkylsulfonylamino, C2-C6 alkenylsulfonylamino, C2-C6
alkylcarbonyl, C2-C6 alkoxycarbonyl, C3-C6 alkenyloxycarbonyl or C3-C6
alkynyloxycarbonyl, wherein each carbon atom is optionally substituted with up
to 1
substituent selected from R10a and up to 3 substituents independently selected
from
R10b.
Embodiment 119. The composition of Embodiment 118 wherein El is C1-C6 alkoxy,
C1-
C6 alkylsulfonyl, C2-C6 alkylcarbonyl or C2-C6 alkoxycarbonyl, wherein each
carbon atom is optionally substituted with up to 1 substituent selected from
R10a and
up to 3 substituents independently selected from R10b.
Embodiment 120. The composition of Embodiment 119 wherein El is C1-C3 alkoxy,
C2-C3 alkylcarbonyl or C2-C3 alkoxycarbonyl, wherein each carbon atom is
optionally substituted with up to 1 substituent selected from R10a and up to 3
substituents independently selected from Rl b.
Embodiment 120a. The composition of Embodiment 120 wherein El is C1-C3 alkoxy
or
C2-C3 alkoxycarbonyl, wherein each carbon atom is optionally substituted with
up
to 1 substituent selected from R10a.
Embodiment 121. The composition of Embodiment 120 wherein El is C1-C2 alkoxy,
wherein each carbon atom is optionally substituted with up to 1 substituent
selected
from R10a and up to 3 substituents independently selected from R10b.
Embodiment 121a. The composition of Embodiment 120 wherein El is C1-C2 alkoxy,
wherein each carbon atom is optionally substituted with up to 1 substituent
selected
from R10a.
Embodiment 12 lb. The composition of Embodiment 121a wherein El is methoxy
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
49
optionally substituted with up to 1 substituent selected from R10a.
Embodiment 121c. The composition of Embodiment 121a wherein El is methoxy
substituted with 1 substituent selected from R10a.
Embodiment 122. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 121c wherein in
Formula 1, R10a is phenyl optionally substituted with up to 3 substituents
independently selected from R11 a; or a 5- to 6-membered heterocyclic ring
containing ring members selected from carbon atoms and 1 to 4 heteroatoms
independently selected from up to 2 0, up to 2 S and up to 4 N atoms, each
ring
optionally substituted with up to 3 substituents independently selected from
R11' on
carbon atom ring members and R1lb on nitrogen atom ring members.
Embodiment 123. The composition of Embodiment 122 wherein R10a is phenyl
optionally
substituted with up to 2 substituents independently selected from R11 a; or a
5- to 6-
membered heterocyclic ring containing ring members selected from carbon atoms
and 1 to 4 heteroatoms independently selected from up to 2 0, up to 2 S and up
to 4
N atoms, each ring optionally substituted with up to 2 substituents
independently
selected from R11' on carbon atom ring members and RI-lb on nitrogen atom ring
members.
Embodiment 123a. The composition of Embodiment 123 wherein R10a is a 5-
membered
heterocyclic ring containing ring members selected from carbon atoms and 1 to
4
heteroatoms independently selected from up to 2 0 and up to 3 N atoms, each
ring
optionally substituted with up to 2 substituents independently selected from
R11' on
carbon atom ring members.
Embodiment 123b. The composition of Embodiment 123a wherein R10a is pyrazolyl,
imidazolyl or triazolyl, each optionally substituted with up to 2 substituents
independently selected from R11' on carbon atom ring members.
Embodiment 123c. The composition of Embodiment 123b wherein R10a is pyrazolyl
or
imidazolyl, each optionally substituted with up to 2 substituents
independently
selected from R11' on carbon atom ring members.
Embodiment 123d. The composition of Embodiment 123c wherein R10a is pyrazolyl
optionally substituted with up to 1 substituent selected from R11' on a carbon
atom
ring member.
Embodiment 124. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 123c wherein in
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
Formula 1, each 1210b is independently cyano, halogen, hydroxy, C1-C4 alkyl,
C1-C4
haloalkyl, C3-C6 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4
alkylsulfonyl,
C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2-C4 dialkylamino, C2-C4
alkylcarbonyl or C2-05 alkoxycarbonyl.
5 Embodiment 125. The composition of Embodiment 124 wherein each 1210b is
independently halogen, hydroxy, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy,
C1-C4 haloalkoxy, C1-C4 alkylsulfonyl, C2-C4 alkylcarbonyl or C2-05
alkoxycarbonyl.
Embodiment 125a. The composition of Embodiment 125 wherein each 1210b is
10 independently halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy or
C2-C4
alkoxycarbonyl.
Embodiment 126. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 125a wherein in
Formula 1, each R11 a is independently halogen, C1-C4 alkyl, C1-C4 haloalkyl,
C2-
15 C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4
alkenyloxy, C2-
C4 alkynyloxy, C2-C4 alkoxyalkyl, C2-C6 alkylcarbonyloxy, C1-C4 alkylsulfonyl,
C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfonyloxy, C2-C4 alkylcarbonyl, C3-05
alkenylcarbonyl, C3-05 alkynylcarbonyl, C2-C6 alkoxycarbonyl, C3-C7
alkenyloxycarbonyl, C3-C7 alkynyloxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C6
20 alkenylaminocarbonyl, C3-C6 alkynylaminocarbonyl or C3-C8
dialkylaminocarbonyl.
Embodiment 127. The composition of Embodiment 126 wherein each R11 a is
independently halogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C1-C4
alkoxy,
C1-C4 haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkoxyalkyl, C2-C4 alkylcarbonyl, C2-
25 C6 alkoxycarbonyl, C3-C7 alkenyloxycarbonyl or C2-C6
alkylaminocarbonyl.
Embodiment 128. The composition of Embodiment 127 wherein each R11 a is
independently halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4
haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl or C3-
05 alkenyloxycarbonyl.
30 Embodiment 128a. The composition of Embodiment 128 wherein each R11a is
independently halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy or C2-C3
alkoxycarbonyl.
Embodiment 128b. The composition of Embodiment 128a wherein each R11 a is
independently methoxycarbonyl or ethoxycarbonyl.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
51
Embodiment 128c. The composition of Embodiment 128b wherein each R11' is
ethoxycarbonyl.
Embodiment 129. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 128c wherein in
Formula 1, each Rub is independently C1-C2 alkyl, C1-C2 alkoxy, C2-C3
alkylcarbonyl or C2-C3 alkoxycarbonyl.
Embodiment 130. The composition of Embodiment 129 wherein each Rub is
independently methyl, methoxy, methylcarbonyl or methoxycarbonyl.
Embodiment 131. The composition of Embodiment 130 wherein each Rub is
independently methyl or methoxy.
Embodiment 132. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 131 wherein in
Formula 1, E is E2.
Embodiment 133. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 132 wherein in
Formula 1, G is phenyl optionally substituted with up to 3 substituents
independently selected from R13; or a 5- to 6-membered heteroaromatic ring,
each
ring containing ring members selected from carbon atoms and 1 to 4 heteroatoms
independently selected from up to 2 0, up to 2 S and up to 4 N atoms, each
ring
optionally substituted with up to 3 substituents independently selected from
R13; or
a 3- to 7-membered nonaromatic ring or an 8- to 11-membered bicyclic ring
system,
each ring or ring system containing ring members selected from carbon atoms
and
optionally up to 4 heteroatoms independently selected from up to 2 0, up to 2
S and
up to 4 N atoms, wherein up to 2 ring members are independently selected from
C(=0), S(=0) and S(=0)2, each ring or ring system optionally substituted with
up to
3 substituents independently selected from R13.
Embodiment 134. The composition of Embodiment 133 wherein G is selected from G-
1
through G-118 as shown in Exhibit A.
Exhibit A
5 5 5 13 5 13
L.
S---R13)x 0'..-R13)x NA sa R )x R
)x
L. . . [..._ . .. .. . . .... õ
2 N 2 N 2 N 2
G-1 G-2 G-3 G-4
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
52
-N 2
2
13 5 13 13
.... R
,\TOR )x ONR
4 , 4 , , s kl3
1...= .....,õ & ,
........ ........
2 2 5 N 5 N
4 4
G-5 G-6 G-7 G-8
2 2 2 2
sal (R13), 0aN (R13), ....-N (R13
N (R13) )x
I.7.........."-x
N i.......;k
,
5 N 5 5 5
4 4 4 4
G-9 G-10 G-11 G-12
2 5 2 ....-N (R13)x 4 2R13
N )1( N .....--(R13)õ 0.*R13 S(
N 1 L.........)&1
,
5 3
4 2 4 4
G-13 G-14 G-15 G-16
3 4
2 R13 2 (R13)x 2 (R13)
N x
....--N (R13)x N, 1 1
N --
I ,....4 ,
, Nt=
,
1 N
2 4 N 4 4
5
G-17 G-18 G-19 G-20
5
2 (R13)x 2 (R13)x (R13),
1 N*N)c 1 1 S.....--R13),
N 4-1\1 3 N.)
N 2 N
4 4 3
G-21 G-22 G-23 G-24
5 5 5 5
0.1R13),
N ---"):13)x ,13)x 13
s".....): ) x
[ . . .= .. . ,...... , I . . . .. .. . ,...... , õ
, 1 . . . . .. . . ,...... ,
2 N 2 N 2 N 2 N
3 3 3 3
G-25 G-26 G-27 G-28
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
53
13 5 13
OaR )x NaR )x 5 (Ri3)x o 5 ,R13 )x
Na4 La4
I 4 I 4
N ------ ,
, 2 2 N ----- -........ ,
.........
2 2 ,
3 3 3 3
G-29 G-30 G-31 G-32 2
13
.....N (RI3)x
4 5
s....c...,5 e(R )x
S 4N....)( (R13)x
4 3 N X
N N
2
1\INif ,
3 2 2
4
G-33 G-34 G-35 G-36
5 5
5 5
10)((lZ13)x 1S----.3((R13)x 4N )(.(R13)x 40' X _....--x
_ (R13),
, ,z0
,
,
2N 2 1\Y N. N.
2 2
G-37 G-38 G-39 G-40
2 (R13)x
(R13)x 13 ,
(R /x (R13)x
3 N41\1
a , NC
- N
4)- ,
5
G-41 G-42 G-43 G-44
2 (R13)x 2 (R13 )x 2 (R13)x
(R13)x
3 3
N ' I -0 1 07/(0 1 S" i -S 1 4 N ,='://1
0 ,
1
4 4 4
G-45 G-46 G-47 G-48
2 (R13)x (R13 ,
bc (R13)x
(R13)x
1 o/ic
3 N S 1 1 SVIC 4
N
S 4 ,
2/ 4 2 S
4 3 1
3
G-49 G-50 G-51 G-52
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
54
8 (R1 3)x 4 (R13)x 4 (R13)x 4 (R13)x
7 ----" 2 , . \ , \ 2 \ 2
\ N 7
N 7 0 0
4 3 8 1 8 1 8 1
G-53 G-54 G-55 G-56
4 (R13 )x 4 (R13)x 4 (R13 )x 4 (R13)x
N
\ N
7 N '
I. 10
7 N 7 S 7 0
8 1 8 1 8 1 8 1
G-57 G-58 G-59 G-60
(R15 x
3)x 5 (R13)x (R13) 5 (R13)x
* 7
N3
, I
N ,_,
7 7 N 7 ' N N
8 1 8 1 8 1 8 1
G-61 G-62 G-63 G-64
5 (R13)x 5 (R13 )x (R13)x (R13)x
5
3 \ 3 1\1,3
I 0 JIL , *
7 *N 7 N
N 7 N
8 1 8 1 8 1
G-65 G-66 G-67 G-68
(R13)x 3 3
. , ai3)õ
, 2 raR13)x
1
5 4 , 2 S (R13)x
1 r44 '
G-69 G-70 G-71 G-72
5 (R13)x
3 3 3 4
2 r......-N (R13)x 2 r..--N (R i3),, 2NaRi3)õ
1, 1, 1 4 ,
, , 01 '
N 0 0 3N y
1 1 1
5 5 5
0
G-73 G-74 G-75 G-76
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
3 3
3 3 0 (R13)x 0 (R13)x
o),...(R4 i 3) 0x Nx(R13 )x
4 4
,
0 1 5 1 5
1 5 1 5
0 0
G-77 G-78 G-79 G-80
1
0N (R13), 3 3 4 (R13), 4 (R13), 4 (R13)õ
3 k rc 5 N 5 NC 5
N4 ' ,
N
2 0 2 N/
4 2 0
0 1 1 1
G-81 G-82 G-83 G-84
(R13)x 13 \ 13 \ (R 13 \
(R h( (R h( hc
1\1
I \ ' I \ , N =-=---*"-.
N
N N N N N
G-85 G-86 G-87 G-88
13, (R13)x (R13)x 13 \ 0
/
N N
N N N
G-89 G-90 G-91 G-92
13 0
(R )õ
,7 3\ 13 1 (R1 h( (R13)x 0:(R )x
0 so ,
oõ....-N
.,......,.7..........1 .. N .. ,
1 ___________________________ 0....-0 '
0
G-93 G-94 G-95 G-96
(R')
3 0
A
(R13)
(R ,x
x % 13\ .x.,,i (R13/x \ x y,
1
1
N
0 0
G-97 G-98 G-99 G-100
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
56
(R13),µ (R13)x (R13)x (R 13 ,
h(
r4.N
N
NO NO N
G-101 G-102 G-103 G-104
,
(R13)x (R13 h( (R13)x
N'%
N,/, N 13 h
,
( __
.........N (R (
x
k , t L ,
- = - , . >
,
N 0 N'O N 0
G-105 G-106 G-107 G-108
(R13) (R 13 ,h (R3)
1 (R13)x
( ( x
.,......,........N 1
.......-,fiks....-.*õ..-N
r/..-----. N _....
/C.- _________________________ .1
7
...I N '
N ------.N/ N
N
G-109 G-110 G-111 G-112
x
(R13)x 0
4 (R13)
(R13)x 5
k\N
/.5
I N /LO , (R 13
)x 6 _N
S
,
NNO
0 0
G-113 G-114 G-115 G-116
(R'3) N-N
13
(/1/1 (R )x 3
and ID N ,
yN
I
CH3
0
G-117 G-118
wherein the floating bond is connected to Z in Formula 1 through any available
carbon or
nitrogen atom of the depicted ring or ring system; and x is 0, 1, 2 or 3.
Embodiment 135. The composition of Embodiment 134 wherein G is G-1 through G-
16,
G-20, G-22 through G-30, G-36 through G-42, G-54 through G-60, G-85, G-86, G-
108, G-110 or G-111.
Embodiment 136. The composition of Embodiment 135 wherein G is G-1 through G-
16,
G-22, G-24, G-25, G-26, G-28, G-29, G-30, G-36, G-37, G-38, G-41, G-42, G-54,
G-57, G-58, G-59, G-60, G-85, G-86, G-108, G-110 or G-111.
Embodiment 137. The composition of Embodiment 136 wherein G is G-1 through G-
13,
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
57
G-22, G-24, G-25, G-26, G-28, G-29, G-41, G-42, G-54, G-57, G-58, G-59 or G-
60.
Embodiment 138. The composition of Embodiment 137 wherein G is G-1, G-2, G-3,
G-7,
G-8, G-9, G-10, G-12, G-13, G-22, G-29, G-42, G-54 or G-58.
Embodiment 139. The composition of Embodiment 138 wherein G is G-1, G-3, G-12,
G-
13, G-22 or G-42.
Embodiment 140. The composition of Embodiment 139 wherein G is G-1, G-3, G-12,
G-
13 or G-22.
Embodiment 141. The composition of Embodiment 140 wherein G is G-1, G-3, G-12
or G-
22.
Embodiment 142. The composition of Embodiment 141 wherein G is G-1 or G-12.
Embodiment 143. The composition of Embodiment 142 wherein G is G-1.
Embodiment 144. The composition of Embodiment 142 wherein G is G-12.
Embodiment 145. The composition of Embodiment 140 wherein G is G-3.
Embodiment 146. The composition of Embodiment 140 wherein G is G-22.
Embodiment 147. The composition of Embodiment 143 wherein the 2-position of G-
1 is
connected to Z and the 4-position is connected to R13.
Embodiment 148. The composition of Embodiment 143 wherein the 2-position of G-
1 is
connected to Z and the 5-position is connected to R13.
Embodiment 149. The composition of Embodiment 144 wherein the 1-position of G-
12 is
connected to Z and the 4-position is connected to R13.
Embodiment 150. The composition of Embodiment 144 wherein the 1-position of G-
12 is
connected to Z and the 3-position is connected to R13.
Embodiment 151. The composition of Embodiment 144 wherein the 1-position of G-
12 is
connected to Z and the 3- and 5-positions are connected to R13.
Embodiment 152. The composition of Embodiment 144 wherein the 1-position of G-
12 is
connected to Z and the 5-position is connected to R13.
Embodiment 153. The composition of Embodiment 145 wherein the 1-position of G-
3 is
connected to Z and the 4-position is connected to R13.
Embodiment 154. The composition of Embodiment 146 wherein the 4-position of G-
22 is
connected to Z and the 2-position is connected to R13.
Embodiment 155. The composition of any one of Embodiments 147 through 154
wherein Z
is a direct bond.
Embodiment 156. The composition of any one of Embodiments 147 through 155
wherein x
is 1 and R13 is methoxycarbonyl or ethoxycarbonyl.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
58
Embodiment 157. The composition of any one of Embodiments 134 through 155
wherein x
is 1 or 2.
Embodiment 158. The composition of Embodiment 157 wherein x is 1.
Embodiment 159. The composition of Embodiment 157 wherein x is 2.
Embodiment 160. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 134 through 155 wherein in
Formula 1, x is 0.
Embodiment 161. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 159 wherein in
Formula 1, each R13 is independently cyano, halogen, NR14aRl4b,
C(=0)NR14aRl4b, c(R15),NR16, N=CR17NR18aRl8b or _u_v_Q; or C1-C6 alkyl,
C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6
alkynyloxy,
C1-C6 alkylsulfonyl, C1-C6 alkylsulfonyloxy, C1-C6 alkylsulfonylamino, C2-C6
alkylcarbonyl, C2-C6 alkoxycarbonyl, C3-C6 alkenyloxycarbonyl, C3-C6
alkynyloxycarbonyl, C4-C7 cycloalkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-C6
alkoxycarbonyloxy, C4-C7 cycloalkoxycarbonyloxy, C2-C6 alkylaminocarbonyloxy,
C2-C6 alkylcarbonylamino, C2-C6 alkoxycarbonylamino or C2-C6
alkylaminocarbonylamino, each optionally substituted with up to 3 substituents
independently selected from R19.
Embodiment 162. The composition of Embodiment 161 wherein each R13 is
independently cyano, halogen, C(=0)NR14aRl4b or _u_v_Q; or C1-C6 alkyl, C2-C6
alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C1-
C6
alkylsulfonyl, C1-C6 alkylsulfonyloxy, C1-C6 alkylsulfonylamino, C2-C6
alkylcarbonyl, C2-C6 alkoxycarbonyl, C3-C6 alkenyloxycarbonyl, C3-C6
alkynyloxycarbonyl or C2-C6 alkoxycarbonyloxy, each optionally substituted
with
up to 3 sub stituents independently selected from R19.
Embodiment 163. The composition of Embodiment 162 wherein each R13 is
independently
C(=0)NR14aRl4b or _u_v_Q; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6
alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C1-C6 alkylsulfonyl, C1-C6
alkylsulfonyloxy, C1-C6 alkylsulfonylamino, C2-C6 alkylcarbonyl, C2-C6
alkoxycarbonyl, C3-C6 alkenyloxycarbonyl, C3-C6 alkynyloxycarbonyl, C4-C6
cycloalkoxycarbonyl or C2-C6 alkoxycarbonyloxy, each optionally substituted
with
up to 3 sub stituents independently selected from R19.
Embodiment 163a. The composition of Embodiment 162 wherein each R13 is
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
59
independently C(=0)NR14aRl4b or _u_v_Q; or C2-05 alkoxycarbonyl, C3-05
alkenyloxycarbonyl, C3-05 alkynyloxycarbonyl or C4-C6 cycloalkoxycarbonyl,
each
optionally substituted with up to 3 substituents independently selected from
R19.
Embodiment 163b. The composition of Embodiment 163a wherein each R13 is
independently C(=0)NR14aRl4b or _u_v_Q; or C2-05 alkoxycarbonyl, C3-05
alkynyloxycarbonyl or C4-C6 cycloalkoxycarbonyl, each optionally substituted
with
up to 1 substituent selected from R19.
Embodiment 164. The composition of Embodiment 163a wherein each R13 is
independently C(=0)NR14aRl4b or _u_v_Q; or C2-C6 alkoxycarbonyl, C3-C6
alkenyloxycarbonyl, C3-C6 alkynyloxycarbonyl or C2-C6 alkoxycarbonyloxy, each
optionally substituted with up to 3 substituents independently selected from
R19.
Embodiment 164a. The composition of Embodiment 164 wherein each R13 is
independently C(=0)NR14aRl4b or _u_v_Q; or C2-C6 alkoxycarbonyl, C3-C6
alkenyloxycarbonyl, or C3-C6 alkynyloxycarbonyl, each optionally substituted
with
up to 3 substituents independently selected from R19.
Embodiment 165. The composition of Embodiment 164a wherein each R13 is
independently C(=0)NR14aRl4b or _u_v_Q; or C2-05 alkoxycarbonyl, C3-05
alkenyloxycarbonyl, or C3-05 alkynyloxycarbonyl, each optionally substituted
with
up to 3 substituents independently selected from R19.
Embodiment 165a. The composition of Embodiment 165 wherein each R13 is
independently C(=0)NR14aRl4b or _u_v_Q; or C2-05 alkoxycarbonyl or C3-05
alkenyloxycarbonyl, each optionally substituted with up to 3 substituents
independently selected from R19.
Embodiment 166. The composition of Embodiment 165 wherein each R13 is
independently
C2-05 alkoxycarbonyl or C3-05 alkenyloxycarbonyl, each optionally substituted
with up to 3 substituents independently selected from R19.
Embodiment 167. The composition of Embodiment 166 wherein each R13 is
independently
C2-05 alkoxycarbonyl, each optionally substituted with up to 3 substituents
independently selected from R19.
Embodiment 168. The composition of Embodiment 167 wherein each R13 is
independently
methoxycarbonyl or ethoxycarbonyl, each optionally substituted with up to 3
substituents independently selected from R19.
Embodiment 169. The composition of Embodiment 168 wherein each R13 is
independently
methoxycarbonyl or ethoxycarbonyl, each optionally substituted with up to 1
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
substituent selected from R19.
Embodiment 170. The composition of Embodiment 169 wherein each R13 is
independently
ethoxycarbonyl optionally substituted with up to 1 substituent selected from
R19.
Embodiment 171. The composition of Embodiment 169 wherein each R13 is
independently
5 methoxycarbonyl or ethoxycarbonyl.
Embodiment 172. The composition of Embodiment 171 wherein each R13 is
ethoxycarbonyl.
Embodiment 173. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 172 wherein in
10 Formula 1, when each R14a is separate (i.e. not taken together with
R14b to form a
ring), then each R14a is independently H, cyano, hydroxy, C1-C4 alkyl, C1-C4
haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 alkynyl, C2-C4 haloalkynyl,
C2-C4 alkylcarbonyl, C2-05 alkoxycarbonyl or C3-05 dialkylaminocarbonyl.
Embodiment 174. The composition of Embodiment 173 wherein each R14a is
15 independently H, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl,
C2-C4
alkynyl, C2-C4 alkylcarbonyl, C2-05 alkoxycarbonyl or C3-05
dialkylaminocarbonyl.
Embodiment 175. The composition of Embodiment 174 wherein each R14a is
independently H, C1-C2 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4
alkylcarbonyl
20 or C2-C4 alkoxycarbonyl.
Embodiment 176. The composition of Embodiment 175 wherein each R14a is
independently H or C1-C2 alkyl.
Embodiment 177. The composition of Embodiment 176 wherein each R14a is
independently H or methyl.
25 Embodiment 177a. The composition of Embodiment 177 wherein each R14a is
H.
Embodiment 178. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 177a wherein in
Formula 1, when each R14b is separate (i.e. not taken together with R14a to
form a
ring), then each R14b is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6
30 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6
cyanoalkyl,
C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C3-C8 cycloalkenyl, C3-C8
halocycloalkenyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C4-C10
halocycloalkylalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6
alkylthioalkyl, C2-C6 alkylsulfonylalkyl, C2-C6 alkylaminoalkyl or C3-C8
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
61
dialkylaminoalkyl, each optionally substituted with up to 1 substituent
selected from
cyano, hydroxy, nitro, C2-C4 alkylcarbonyl or C2-C4 alkoxycarbonyl.
Embodiment 179. The composition of Embodiment 178 wherein each R14b is
independently H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4
haloalkenyl,
C2-C4 alkynyl, C3-05 cycloalkyl, C4-C6 cycloalkylalkyl, C2-C4 alkoxyalkyl, C2-
C4
haloalkoxyalkyl, C2-C4 alkylaminoalkyl or C3-05 dialkylaminoalkyl.
Embodiment 180. The composition of Embodiment 179 wherein each R14b is
independently H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, C2-C4
haloalkenyl,
C3-05 cycloalkyl, C4-C6 cycloalkylalkyl or C2-C4 alkoxyalkyl.
Embodiment 181. The composition of Embodiment 180 wherein each R14b is
independently H, C1-C3 alkyl, C1-C3 haloalkyl, cyclopropylmethyl or C2-C4
alkoxyalkyl.
Embodiment 181a. The composition of Embodiment 181 wherein each R14b is
independently H, C1-C2 alkyl, C1-C2 haloalkyl or cyclopropylmethyl.
Embodiment 181b. The composition of Embodiment 181a wherein each R14b is
independently H, methyl or cyclopropylmethyl.
Embodiment 182. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 181b wherein in
Formula 1, when R14a and R14b are taken together to form a 4- to 6-membered
fully
saturated heterocyclic ring, then said ring contains ring members, in addition
to the
connecting nitrogen atom, selected from carbon atoms and up to 1 heteroatom
selected from up to 1 0, up to 1 S and up to 1 N atom, each ring optionally
substituted with up to 2 substituents independently selected from halogen or
methyl.
Embodiment 183. The composition of Embodiment 182 wherein R14a and R14b are
taken
together to form an azetidinyl, morpholinyl, pyrrolidinyl, piperidinyl,
piperazinyl or
thiomorpholinyl ring, each ring optionally substituted with up to 2
substituents
independently selected from halogen or methyl.
Embodiment 184. The composition of Embodiment 183 wherein R14a and R14b are
taken
together to form an azetidinyl or pyrrolidinyl ring, each ring optionally
substituted
with up to 2 substituents independently selected from halogen or methyl.
Embodiment 185. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 184 wherein in
Formula 1, each R15 is independently H, cyano, halogen, methyl or methoxy.
Embodiment 186. The composition of Embodiment 185 wherein each R15 is
independently
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
62
H or methyl.
Embodiment 187. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 186 wherein in
Formula 1, each R16 is independently hydroxy, NR20aR20b, C1-C2 alkoxy, C2-C4
alkenyloxy, C2-C4 alkylcarbonyloxy or C2-C4 alkoxycarbonyloxy.
Embodiment 188. The composition of Embodiment 187 wherein each R16 is
independently
hydroxy, NR20aR20b or C1-C4 alkoxy.
Embodiment 189. The composition of Embodiment 188 wherein each R16 is
independently
hydroxy, NR20aR20b or methoxy.
Embodiment 190. The composition of Embodiment 189 wherein each R16 is hydroxy.
Embodiment 191. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 190 wherein in
Formula 1, each R17 is independently H or methyl.
Embodiment 192. The composition of Embodiment 191 wherein each R17 is H.
Embodiment 193. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 192 wherein in
Formula 1, when each R18a and R18b is separate (i.e. not taken together to
form a
ring), then each R18a and R18b is independently H, methyl or ethyl.
Embodiment 194. The composition of Embodiment 193 wherein each R18a and R18b
is
independently H or methyl.
Embodiment 195. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 194 wherein in
Formula 1, when R18a and R18b are taken together to form a 5- to 6-membered
fully
saturated heterocyclic ring, then said ring contains ring members, in addition
to the
connecting nitrogen atom, selected from carbon atoms and up to 1 heteroatom
selected from up to 1 0, up to 1 S and up to 1 N atom, each ring optionally
substituted with up to 2 methyl groups.
Embodiment 196. The composition of Embodiment 195 wherein R18a and R18b are
taken
together to form an azetidinyl, morpholinyl, pyrrolidinyl, piperidinyl,
piperazinyl, or
thiomorpholinyl ring, each ring optionally substituted with up to 2 methyl
groups.
Embodiment 197. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 196 wherein in
Formula 1, each R19 is independently cyano, halogen, hydroxy, C1-C3 alkyl, C1-
C3
haloalkyl, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C3
alkoxyalkoxy,
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
63
C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3
haloalkylsulfonyl,
C2-C3 alkylcarbonyl, C2-C3 haloalkylcarbonyl, C2-C3 alkoxycarbonyl, C2-C3
alkylaminocarbonyl or C3-05 dialkylaminocarbonyl.
Embodiment 198. The composition of Embodiment 197 wherein each R19 is
independently
cyano, halogen, hydroxy, C1-C2 alkyl, C1-C2 haloalkyl, C3-C6 cycloalkyl, C1-C2
alkoxy, C1-C2 haloalkoxy, C1-C2 alkylthio, C1-C2 alkylsulfonyl, C1-C2
haloalkylsulfonyl, C2-C3 alkylcarbonyl, C2-C3 haloalkylcarbonyl, C2-C3
alkoxycarbonyl or C2-C3 alkylaminocarbonyl.
Embodiment 199. The composition of Embodiment 197 wherein each R19 is
independently
cyano, halogen, C1-C2 alkyl, C1-C2 haloalkyl, C3-C6 cycloalkyl, C1-C2 alkoxy,
C1-C2 haloalkoxy, C2-C3 alkylcarbonyl, C2-C3 haloalkylcarbonyl or C2-C3
alkoxycarbonyl.
Embodiment 200. The composition of Embodiment 199 wherein each R19 is
independently
cyano, halogen, cyclopropyl, cyclobutyl, methoxy, halomethoxy or
methoxycarbonyl.
Embodiment 200a. The composition of Embodiment 200 wherein each R19 is
independently cyano, halogen, cyclopropyl or methoxy.
Embodiment 200b. The composition of Embodiment 200a wherein each R19 is
independently cyano, Cl, F, cyclopropyl or methoxy.
Embodiment 201. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 200b wherein in
Formula 1, each U is independently a direct bond, C(=0)0 or C(=0)N(R25).
Embodiment 202. The composition of Embodiment 201 wherein each U is
independently a
direct bond or C(=0)0.
Embodiment 203. The composition of Embodiment 202 wherein each U is C(=0)0.
Embodiment 204. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 203 wherein in
Formula 1, each V is independently a direct bond; or C1-C6 alkylene, C2-C6
alkenylene or C3-C6 alkynylene, each optionally substituted with up to 2
substituents independently selected from halogen, cyano, nitro, hydroxy, C1-C2
alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy.
Embodiment 205. The composition of Embodiment 204 wherein each V is
independently a
direct bond; or C1-C3 alkylene, each optionally substituted with up to 2
substituents
independently selected from halogen, hydroxy, C1-C2 alkyl, C1-C2 alkoxy and
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
64
C1-C2 haloalkoxy.
Embodiment 206. The composition of Embodiment 205 wherein each V is
independently a
direct bond or C1-C3 alkylene.
Embodiment 207. The composition of Embodiment 206 wherein each V is
independently a
direct bond or CH2.
Embodiment 208. The composition of Embodiment 207 wherein each V is a direct
bond.
Embodiment 209. The composition of Embodiment 207 wherein each V is
independently
C1-C2 alkylene.
Embodiment 210. The composition of Embodiment 209 wherein each V is CH2.
Embodiment 211. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 210 wherein in
Formula 1, each Q is independently phenyl optionally substituted with up to 2
substituents independently selected from R27; or a 5- to 6-membered
heteroaromatic
ring, each ring containing ring members selected from carbon atoms and 1 to 4
heteroatoms independently selected from up to 2 0, up to 2 S and up to 4 N
atoms,
each ring optionally substituted with up to 2 substituents independently
selected
from R27; or a 3- to 6-membered nonaromatic heterocyclic ring, each ring
containing ring members selected from carbon atoms and 1 to 4 heteroatoms
independently selected from up to 2 0, up to 2 S and up to 4 N atoms, wherein
up to
2 ring members are independently selected from C(=0), C(=S), S(=0) and S(=0)2,
each ring optionally substituted with up to 2 substituents independently
selected
from R27.
Embodiment 212. The composition of Embodiment 210 wherein each Q is
independently
phenyl optionally substituted with up to 2 substituents independently selected
from
R27; or pyridinyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl,
isoxazolyl,
thienyl, isoxazolinyl, piperidinyl, morpholinyl or piperazinyl, each
optionally
substituted with up to 2 substituents independently selected from R27.
Embodiment 213. The composition of Embodiment 212 wherein each Q is
independently
phenyl optionally substituted with up to 2 substituents independently selected
from
R27; or pyridinyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl or oxazolyl,
each
optionally substituted with up to 2 substituents independently selected from
R27.
Embodiment 214. The composition of Embodiment 213 wherein each Q is
independently
phenyl optionally substituted with up to 2 substituents independently selected
from
R27; or pyridinyl or pyrazolyl, each optionally substituted with up to 2
substituents
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
independently selected from R27.
Embodiment 214a. The composition of Embodiment 214 wherein each Q is
independently
phenyl or pyridinyl, each optionally substituted with up to 2 substituents
independently selected from R27.
5 Embodiment 214b. The composition of Embodiment 214a wherein each Q is
independently phenyl optionally substituted with up to 2 substituents
independently
selected from R27.
Embodiment 215. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 214b wherein in
10 Formula 1, when each R20a is separate (i.e. not taken together with
R20b to form a
ring), then each R20a is independently H, methyl or methylcarbonyl.
Embodiment 216. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 215 wherein in
Formula 1, when each R20b is separate (i.e. not taken together with R20a to
form a
15 ring), then each R20b is independently H, cyano, methyl,
methylcarbonyl,
methoxycarbonyl, methoxycarbonylmethyl, methylaminocarbonyl or
dimethylaminocarbonyl.
Embodiment 217. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 216 wherein in
20 Formula 1, when R20a and R20b are taken together to form a 5- to 6-
membered fully
saturated heterocyclic ring, then said ring contains ring members, in addition
to the
connecting nitrogen atom, selected from carbon atoms and up to 1 heteroatom
selected from up to 1 0, up to 1 S and up to 1 N atom, each ring optionally
substituted with up to 2 methyl groups.
25 Embodiment 218. The composition of Embodiment 217 wherein R20a and R20b
are taken
together to form an azetidinyl, morpholinyl, pyrrolidinyl, piperidinyl,
piperazinyl or
thiomorpholinyl ring, each ring optionally substituted with up to 2 methyl
groups.
Embodiment 219. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 218 wherein in
30 Formula 1, each R21 and R23 is independently H, cyano, halogen,
methyl or
methoxy.
Embodiment 220. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 219 wherein in
Formula 1, each R22 is independently H, C1-C3 alkyl, C1-C3 haloalkyl, C2-C3
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
66
alkylcarbonyl or C2-C3 alkoxycarbonyl; or phenyl optionally substituted with
up to
2 substituents independently selected halogen and methyl; or a 5- to 6-
membered
fully saturated heterocyclic ring, each ring containing ring members selected
from
carbon atoms and up to 2 heteroatoms independently selected from up to 2 0, up
to
2 S and up to 2 N atoms, each ring optionally substituted with up to 2
substituents
independently selected from halogen and methyl.
Embodiment 221. The composition of Embodiment 220 wherein each R22 is
independently
H or C1-C2 alkyl.
Embodiment 222. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 221 wherein in
Formula 1, each R24 is independently H, cyano or C1-C2 alkyl.
Embodiment 223. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 222 wherein in
Formula 1, each R25 and R26 is independently H, cyano, hydroxy, C1-C4 alkyl or
C1-C4 haloalkyl.
Embodiment 224. The composition of Embodiment 223 wherein each R25 and R26 is
independently H, cyano, hydroxy or C1-C2 alkyl.
Embodiment 225. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 224 wherein in
Formula 1, each R27 is independently halogen, cyano, C1-C4 alkyl, C1-C4
haloalkyl
or C1-C4 alkoxy.
Embodiment 226. The composition of Embodiment 225 wherein each R27 is
independently
halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl or C1-C2 alkoxy.
Embodiment 227. The composition of Embodiment 226 wherein each R27 is
independently
halogen, methyl or methoxy.
Embodiment 228. The composition of Embodiment 227 wherein each R27 is
independently
halogen.
Embodiment 229. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 228 wherein in
Formula 1, Z is a direct bond, 0, NH, C(=0), C(=0)NH, NHC(=0), NHC(=0)NH,
OC(=0)NH, NHC(=0)0, S(=0)2NH, NHS(=0)2 or NHS(=0)2NH.
Embodiment 230. The composition of Embodiment 229 wherein Z is a direct bond,
0, NH,
C(=0), C(=0)NH or NHC(=0).
Embodiment 231. The composition of Embodiment 230 wherein Z is a direct bond,
0, NH
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
67
or C(=0).
Embodiment 232. The composition of Embodiment 231 wherein Z is a direct bond.
Embodiment 233. The composition of Formula 1 or any one of Embodiments 1
through
232 wherein each R28 is independently H or C1-C3 alkyl.
Embodiment 234. The composition of Embodiment 233 wherein each R28 is
independently
H or methyl.
Embodiment 235. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 234 wherein in
Formula 1, m is 0 or 2.
Embodiment 236. The composition of Embodiment 235 wherein m is 2.
Embodiment 237. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 236 wherein
component (a) does not comprise an N-oxide of a compound of Formula 1.
Embodiment 238. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 236 wherein
component (a) comprises a compound selected from the group consisting of
ethyl 1-[[4-(3,3,3-trifluoro-2,2-dihydroxypropoxy)phenyl]methy1]-1H-pyrazole-4-
carboxylate
(Compound 1);
ethyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methy1]-1H-
pyrazole-4-
carboxylate (Compound 32);
ethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methy1]-
1H-pyrazole-4-
carboxylate (Compound 64);
ethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methy1]-
1H-pyrazole-3-
carboxylate (Compound 231);
ethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]-3-
fluorophenyl]methy1]-1H-
pyrazole-4-carboxylate (Compound 262);
ethyl 1-[[3-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methy1]-
1H-pyrazole-4-
carboxylate (Compound 265);
ethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenoxy]methy1]-
1H-pyrazole-
4-carboxylate (Compound 364);
N-(cyclopropylmethyl)-2-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxy]pheny1]-
methyl]thiazole-4-carboxamide (Compound 71);
2-methylpropyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxy]phenyl]methy1]-1H-
pyrazole-4-carboxylate (Compound 126);
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
68
cyclopropylmethyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxy]phenyl]methy1]-
1H-pyrazole-4-carboxylate (Compound 127);
ethyl 1-[2-[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]ethy1]-
1H-pyrazole-4-
carboxylate (Compound 132);
2-methoxyethyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxy]phenyl]methy1]-1H-
pyrazole-4-carboxylate (Compound 162);
2-butyn-1-y1 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxy]phenyl]methy1]-1H-
pyrazole-4-carboxylate (Compound 163);
3-cyanopropyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxy]phenyl]methy1]-1H-
pyrazole-4-carboxylate (Compound 171);
phenylmethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-
yl]oxy]phenyl]methy1]-1H-
pyrazole-4-carboxylate (Compound 186);
butyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methy1]-
1H-pyrazole-4-
carboxylate (Compound 218);
3-chloropropyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-
yl]oxy]phenyl]methy1]-1H-
pyrazole-4-carboxylate (Compound 221);
methyl 4-(3,3,3-trifluoro-2,2-dihydroxypropoxy)phenylcarboxylate (Compound
229);
ethyl 1-[[3-fluoro-4-[[2-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxy]phenyl]methy1]-1H-
pyrazole-4-carboxylate (Compound 263);
ethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-
yl]oxy]phenylmethoxy]methy1]-1H-
pyrazole-4-carboxylate (Compound 297);
methyl 1-[[3-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methy1]-
1H-pyrazole-
4-carboxylate (Compound 330); and
propyl 1-[[3-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-yl]oxy]phenyl]methy1]-
1H-pyrazole-
4-carboxylate (Compound 331).
Embodiment 239. The composition of Embodiment 238 wherein component (a)
comprises
a compound selected from the group consisting of Compounds 32, 64, 71, 126,
127,
132, 162, 163, 171, 186, 218, 229, 263, 297, 330 and 331.
Embodiment 240. The composition of Embodiment 239 wherein component (a)
comprises
a compound selected from the group consisting of Compounds 32, 64, 71, 126,
127,
132, 162, 163, 171, 218, 229 and 263.
Embodiment 241. The composition of Embodiment 240 wherein component (a)
comprises
a compound selected from the group consisting of Compounds 32, 64, 126, 127,
132, 162, 163, 171 and 263.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
69
Embodiment 242. The composition of Embodiment 241 wherein component (a)
comprises
a compound selected from the group consisting of Compounds 32, 64, 126, 132,
163
and 263.
Embodiment 243. The composition of Embodiment 242 wherein component (a)
comprises
a compound selected from the group consisting of Compounds 32 and 64.
Embodiment 243a. The composition of Embodiment 243 wherein component (a) is
Compound 32.
Embodiment 243b. The composition of Embodiment 243 wherein component (a) is
Compound 64.
Embodiment 244. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is ethyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxy]phenyl]methy1]-1H-pyrazole-4-carboxylate, its (E)-isomer or a
mixture
thereof.
Embodiment 245. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is ethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-
yl]oxy]phenyl]methy1]-1H-pyrazole-4-carboxylate, its (E)-isomer or a mixture
thereof.
Embodiment 246. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is ethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-
yl]oxy]-3-
fluorophenyl]methy1]-1H-pyrazole-4-carboxylate, its (E)-isomer or a mixture
thereof.
Embodiment 247. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is ethyl 1-[[3-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-
yl]oxy]phenyl]methy1]-1H-pyrazole-4-carboxylate, its (E)-isomer or a mixture
thereof.
Embodiment 248. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is ethyl 1-[[4-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-
yl]oxy]phenoxy]methy1]-1H-pyrazole-4-carboxylate, its (E)-isomer or a mixture
thereof.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
Embodiment 249. The composition comprising components (a) and (b) described in
the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is ethyl 1- [2-[4- [[(1Z)-2-ethoxy-3,3,3-trifluoro-l-propen-l-
yl]oxy]phenyl]ethyl]-1H-pyrazole-4-carboxylate, its (E)-isomer or a mixture
thereof.
5 Embodiment 250. The composition comprising components (a) and (b)
described in the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is phenylmethyl 1- [ [4- [ [(1Z)-2-ethoxy-3 ,3 ,3 -trifluoro-1 -
propen- 1-
yl]oxy]phenyl]methy1]-1H-pyrazole-4-carboxylate, its (E)-isomer or a mixture
thereof.
10 Embodiment 251. The composition comprising components (a) and (b)
described in the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is butyl 1- [ [4- [[(1Z)-2-ethoxy-3,3,3-trifluoro-l-propen-l-
yl]oxy]phenyl]methy1]-1H-pyrazole-4-carboxylate, its (E)-isomer or a mixture
thereof.
15 Embodiment 252. The composition comprising components (a) and (b)
described in the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is 3 -chloropropyl 1- [ [4- [ [(1Z)-2-ethoxy-3 ,3 ,3 -trifluoro-
1 -propen- 1-
yl]oxy]phenyl]methy1]-1H-pyrazole-4-carboxylate, its (E)-isomer or a mixture
thereof.
20 Embodiment 253. The composition comprising components (a) and (b)
described in the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is ethyl 1- [ [4- [[(1Z)-2-ethoxy-3,3,3-trifluoro-l-propen-l-
yl]oxy]phenylmethoxy]methyl]-1H-pyrazole-4-carboxylate, its (E)-isomer or a
mixture thereof.
25 Embodiment 254. The composition comprising components (a) and (b)
described in the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is methyl 1- [ [3 - [[(1Z)-2-ethoxy-3,3,3-trifluoro-l-propen-l-
yl]oxy]phenyl]methy1]-1H-pyrazole-4-carboxylate, its (E)-isomer or a mixture
thereof.
30 Embodiment 255. The composition comprising components (a) and (b)
described in the
Summary of the Invention or any one of Embodiments 1 through 243 wherein
component (a) is propyl 14[3-[[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-
yl]oxy]phenyl]methy1]-1H-pyrazole-4-carboxylate, its (E)-isomer or a mixture
thereof.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
71
Embodiment 256. The composition of Embodiments 238 through 255 wherein wherin
component (b) comprises at least two fungicidal compounds, and when component
(b) consists of a binary combination of two fungicidal compounds, wherein one
of
the fungicidal compounds is cyproconazole, difenconazole, epoxiconazole,
flutriafol, metconazole, prothioconazole or tebuconazole then the other
fungicidal
compound is other than azoxystrobin, benzovindiflupyr, bixafen, boscalid,
fluopyram, luindapyr, fluxapyroxad, isopyrazam, kresoxim-methyl, penthiopyrad,
picoxystrobin, proquinazid, pyraclostrobin, quinoxyfen, sedaxane or
trifloxystrobin.
Embodiment 257. The composition of Embodiments 238 through 256 wherein wherin
component (b) comprises at least two fungicidal compounds, and when component
(b) consists of a binary combination of two fungicidal compounds, wherein one
of
the fungicidal compounds is cyproconazole, difenconazole, epoxiconazole,
flutriafol, prothioconazole or tebuconazole then the other fungicidal compound
is
other than azoxystrobin, benzovindiflupyr, bixafen, fluindapyr, fluxapyroxad,
isopyrazam, picoxystrobin, pyraclostrobin, or trifloxystrobin.
Embodiment 258. The composition of Embodiment 257 wherein (b) comprises at
least two
fungicidal compounds, and when component (b) consists of a binary combination
of
two fungicidal compounds, wherein one of the fungicidal compounds is
cyproconazole, difenconazole, epoxiconazole, flutriafol, prothioconazole or
tebuconazole then the other fungicidal compound is other than azoxystrobin,
benzovindiflupyr, bixafen, fluindapyr, fluxapyroxad, isopyrazam,
picoxystrobin,
pyraclostrobin or trifloxystrobin.
Embodiments of this invention, including Embodiments 1-258 above as well as
any other
embodiments described herein, can be combined in any manner, and the
descriptions of variables
in the embodiments not only to the compositions comprising compounds of
Formula 1 with at
least one other fungicidal compound but also to compositions comprising
compounds of Formula
1 with at least one invertebrate pest control compound or agent, and also to
the compounds of
Formula 1 and their compositions, and also to the starting compounds and
intermediate
compounds useful for preparing the compounds of Formula 1. In addition,
embodiments of this
invention, including Embodiments 1-258 above as well as any other embodiments
described
herein, and any combination thereof, pertain to the methods of the present
invention. Therefore
of note as a further embodiment is the composition disclosed above comprising
(a) at least one
compound selected from the compounds of Formula 1 described above, N-oxides,
and salts
thereof; and at least one invertebrate pest control compound or agent.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
72
Combinations of Embodiments 1-258 are illustrated by:
Embodiment A. The composition comprising components (a) and (b) described
Summary of the
Invention wherein component (a) comprises a compound of Formula 1 or salt
thereof,
wherein in Formula 1,
R1 is CF3, CC13 or CF2C1;
W is 0;
R5a and R5b are each independently H, hydroxy or methyl;
R2a and R2b are each independently H or methyl; or
R2a and R2b are taken together with the atoms X and Y to which they are
attached to form a
5- to 6-membered saturated ring containing ring members, in addition to the
atoms
X and Y, selected from carbon atoms, wherein up to 1 carbon atom ring member
is
selected from C(=0), the ring optionally substituted with up to 2 substituents
independently selected from halogen, cyano, methyl, halomethyl, methoxy and
halomethoxy on carbon atom ring members;
R2c is C1-C2 alkyl, C2-C3 alkenyl or C2-C3 alkynyl;
R2d is H or methyl;
A1 is cR6cR6d or 0;
A2 is a direct bond, CR6eR6f or 0;
R6a, R6b, R6c, R6d, R6e and R6f are each independently H, cyano, hydroxy, Br,
Cl, F or
methyl;
J is J-1, J-6 or J-14;
each R8 is independently F, Cl or methyl;
each R9a and R9b is independently H, halogen or methyl;
n is 0, 1 or 2;
El is C1-C6 alkoxy, C1-C6 alkylsulfonyl, C2-C6 alkylcarbonyl or C2-C6
alkoxycarbonyl,
wherein each carbon atom is optionally substituted with up to 1 substituent
selected
from R10a and up to 3 substituents independently selected from RlOb;
R10a is phenyl optionally substituted with up to 2 substituents independently
selected from
Ri I a; or a 5- to 6-membered heterocyclic ring containing ring members
selected
from carbon atoms and 1 to 4 heteroatoms independently selected from up to 2
0, up
to 2 S and up to 4 N atoms, each ring optionally substituted with up to 2
substituents
independently selected from R11' on carbon atom ring members and Rub on
nitrogen atom ring members;
each RlOb is independently halogen, hydroxy, C1-C4 alkyl, C1-C4 haloalkyl, C1-
C4 alkoxy,
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
73
C1-C4 haloalkoxy, C1-C4 alkylsulfonyl, C2-C4 alkylcarbonyl or C2-05
alkoxycarbonyl;
each R11' is independently halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy
or C2-C3
alkoxycarbonyl;
each R1 lb is independently methyl, methoxy, methylcarbonyl or
methoxycarbonyl;
G is selected from the group consisting of:
5 5 13 5 13 5 13
S-X(R13 )x ) x
,4 , 4 , 4
,
L............ ....,
2 N 2c N 2 N 2
G-1 G-2 G-3 G-4
2 2
5 13 R13
0,R )x 1\10R )x
1..............-N&R13
4 , 4 , k
,
,
......, ........
2 2 51----N 5 N
4 4
G-5 G-6 G-7 G-8
2 2 2 2
13) ,===N (R13)x .....-13
,Rx
0N(R13) x
NN (R )
I .,.j -Ts...
, S.:x
4 4 4 4
G-9 G-10
4 N....,sc(R13)x G-11 G-12
2 2 13 2 13
N X CIR
S<R
N 1
...1...1 , 1,-...z....õ11
5 3 NY 5 N 5 N
4 2 4 4
G-13 G-14 G-15 G-16
3 4
2 N R13 2 (R13)x 2 (R13
NN (R13)x , 1 1
N ---
N N Nc
I A4 I :5
N---- NNj-
1 5 2 1 N 4 4
G-17 G-18 G-19 G-20
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
74
(R )7( 2 (R13)x (03)x
1N*1\1)c 1 1 S'''......R13)x
N N 3 N
2 N
4 4 3
G-21 G-22 G-23 G-24
5 5 , 5
........x(R13 1
)x : 13),( a(R '''')x S..
..--LR13)x
0 .7:
, 1........,, ,
2 L---1\1)C 2 N 2 N 2 N''
3 3 3 3
G-25 G-26 G-27 G-28
5 13 5 13
035: )x NaR )x 5 (Ri3)x 5 ,R13 )x
, Na4
oa4
1 4 I 4
N ----- ,
2 N ----- -......... , .........
2 2 2 ,
3 3 3 3
G-29 G-30 G-31 G-32
......2N (RI3)x
5 13 5
SaR )x 4 (R13)x 4N >((R13)x
4
= 3 , N X
N I N
,
.........
2
5 1\1%if
3 2 2
4
G-33 G-34 G-35 G-36
5 5
5 5
10.....)((R13)x I S>((1Z13)x 4N'..)(.(R13)x 40' X _...--x _(R13),
'
,
2 2 1,1
2 2
G-37 G-38 G-39 G-40
2 (R13)x
a x
(R13) (R13)
c (R13)x
3 N41\T , N
_ NII
' N ,
4)- ,
5
G-41 G-42 G-43 G-44
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
(R13)x
2 (R13)x 2 (R13)x 2 (R13)x
1
1
4 4 4
G-45 G-46 G-47 G-48
2 (R13)x 13\
(R hc (R (R13)
13)x
x
3 1 0/1 1 sVic
4
N' ' -S 1 N
, 1
,
S 4 ,
2/ 4 2
4 3
3
G-49 G-50 G-51 G-52
8 (R13)x 4 (R13)x 4 (R13)x 4 (R13)x
7 ------' 0 \
\ 2 \ 2
2 , ,
N 7
N 7 0 0 '
4 3 8 1 8 1 8 1
G-53 G-54 G-55 G-56
4 (R13 )x 4 (R13)x 4 (R13)x 4 (R13)x
N
, \ N \ N 2
N 2
0 * , *
'
7 1.1 N 7
8 1 8 1 8 1 8 1
G-57 G-58 G-59 G-60
5 (R13)x 5 (R13 )x 5 (R13 )x 5 (R13)x
0 N3N¨ 3 3 3
7 7 N 7 7 N N
8 1 8 1 8 1 8 1
G-61 G-62 G-63 G-64
)x 5 (R13)x (R13)x (R13)
5 (R13 x
5
\ N 33
I N 10 ¨H ,
7 ,. 7 N
7 N
8 1 8 1 8 1
G-65 G-66 G-67 G-68
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
76
1 3S (R13)x
(03)x 3
* , 3 2
a
)õ 2 0 (R13)x
,
, 0
, ..........4
S
5 ,
G-69 G-70 G-71 G-72
5 (03)x
3 3
2 raR13)x 3 4
2 rõ....-N (R13)x 2N,R13)x
1,4 I 4 , , , ,
3N y0
N 0 0 1
I 5 1 5 1 5
0
G-73 G-74 G-75 G-76
3 3
3 3 0 (R13)x 0
0 13 (R13)x
o),....:2,1:13)x Nx(R )x
4 4
O 1 5 1 5
5
0 0
G-77 G-78 G-79 G-80
1
04R13)x 4 (R13)x 4 (R13)x 4 (R13)x
3 3 3 rc 5 N 5 NC 5
5 I -
k k
N '
N
2 0 2 N/
4 2 0
0 1 1 1
G-81 G-82 G-83 G-84
(R
13)x (R13) (R 13 \h R 13 h
\
( ( ((
N
N \
N N N N N
G-85 G-86 G-87 G-88
13\ (R13)x (R13)x 13 \ 0
(R /x (R /x B
N( I N< ' 0
N '
N N
N N/ , I" -J----***N
G-89 G-90 G-91 G-92
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
77
(R13)x
I / 0
(R'')x
13 , 13
,7 1 (R (x (R L))
i
.....--N 0
.,...,...v....i 9Z ,
.------N1 N N
0
G-93 G-94 G-95 G-96
0
%
(EZ13 )x 3 , (R13)x
A \ (R1 ,x yx...s.\. (R13)x
i
1
N
0
G-97 98 -,( 0
(R/ G-99 G-100
(R1)
(R13/x (R13)x 13,
x
' 1 ' I ' II '
NO No N N
N
G-101 G-102 G-103 G-104
(R13)x (R13)x (R13)x
N
(IV
/V,
, - N ......-N (R13)x
k ______
t _______________________________________________ ,
----_.> ,
Ni) NO
N 0
G-105 G-106 G-107 G-108
(R13)x (R13)x (R13)x (R13)x
c...------*--- ".......-1
N '
rCI------ACT I ' NUs....
1\1/
N===.,õ,,,,..:N/ N/ I
G-109 G-110 G-111 G-112
4 (R13)x
(R13), (R13)x 0
N 04 IN 5
.5
I I
NNO ' N /L0 (R13)\U 6
1\1
S
0 0
G-113 G-114 G-115 G-116
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
78
(R13),
N¨N
0/1 (R13)x.... . A _
yN and o'N/\1>c 3 ,
CH3
0
G-117 G-118
wherein the floating bond is connected to Z in Formula 1 through any available
carbon or
nitrogen atom of the depicted ring or ring system; and x is 0, 1, 2 or 3;
each R13 is independently C(=0)NR14aRl4b or _i_j_v_Q; or C1-C6 alkyl, C2-C6
alkenyl,
C2-C6 alkynyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C1-C6
alkylsulfonyl, C1-C6 alkylsulfonyloxy, C1-C6 alkylsulfonylamino, C2-C6
alkylcarbonyl, C2-C6 alkoxycarbonyl, C3-C6 alkenyloxycarbonyl, C3-C6
alkynyloxycarbonyl, C4-C6 cycloalkoxycarbonyl or C2-C6 alkoxycarbonyloxy, each
optionally substituted with up to 3 substituents independently selected from
R19;
each R14a is independently H, C1-C2 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4
alkylcarbonyl or C2-C4 alkoxycarbonyl;
each R14b is independently H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-
C4
haloalkenyl, C2-C4 alkynyl, C3-05 cycloalkyl, C4-C6 cycloalkylalkyl, C2-C4
alkoxyalkyl, C2-C4 haloalkoxyalkyl, C2-C4 alkylaminoalkyl or C3-05
dialkylaminoalkyl; or
R14a and R14b are taken together to form an azetidinyl, morpholinyl,
pyrrolidinyl,
piperidinyl, piperazinyl or thiomorpholinyl ring, each ring optionally
substituted
with up to 2 substituents independently selected from halogen or methyl;
each R19 is independently cyano, halogen, C1-C2 alkyl, C1-C2 haloalkyl, C3-C6
cycloalkyl,
C1-C2 alkoxy, C1-C2 haloalkoxy, C2-C3 alkylcarbonyl, C2-C3 haloalkylcarbonyl
or
C2-C3 alkoxycarbonyl;
each U is independently a direct bond, C(=0)0 or C(=0)N(R25);
each V is independently a direct bond; or C1-C3 alkylene, each optionally
substituted with
up to 2 substituents independently selected from halogen, hydroxy, C1-C2
alkyl,
C1-C2 alkoxy and C1-C2 haloalkoxy;
each Q is independently phenyl optionally substituted with up to 2
substituents
independently selected from R27; or pyridinyl, pyrazolyl, imidazolyl,
triazolyl,
thiazolyl or oxazolyl, each optionally substituted with up to 2 substituents
independently selected from R27;
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
79
each R25 is independently H, cyano, hydroxy or C1-C2 alkyl;
each R27 is independently halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl or C1-
C2 alkoxy;
and
Z is a direct bond, 0, NH, C(=0), C(=0)NH, NHC(=0), NHC(=0)NH, 0C(=0)NH,
NHC(=0)0, S(=0)2NH, NHS(=0)2 or NHS(=0)2NH.
Embodiment AA. The composition of Embodiment A wherein in Formula 1,
R1 is CF3;
X is 0;
Y is 0;
L is a direct bond or CH2; and
Z is a direct bond.
Embodiment AAA. The composition of Embodiment A wherein in Formula 1,
R1 is CF3;
Z is a direct bond.
Embodiment B. The composition of Embodiment A wherein in Formula 1,
T is T-2 or T-3;
R1 is CF3;
X is 0;
Y is 0;
R2a and R2b are each independently H or methyl; or
R2a and R2b are taken together with the atoms X and Y to which they are
attached to form a
5-membered saturated ring containing ring members, in addition to the atoms X
and
Y, selected from carbon atoms, the ring optionally substituted with up to 1
substituent selected from halogen, methyl and halomethyl on a carbon atom ring
member;
R2c is methyl or ethyl;
R2d is H;
Al is 0;
A2 is a direct bond or CH2;
R6a and R6b are each independently H, cyano hydroxy or methyl;
J is J-1 or J-6;
q is 0 or 1;
each R9a and R9b is independently H or methyl;
El is C1-C3 alkoxy, C2-C3 alkylcarbonyl or C2-C3 alkoxycarbonyl, wherein each
carbon
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
atom is optionally substituted with up to 1 substituent selected from R113a
and up to 3
substituents independently selected from R10b;
R10a is pyrazolyl, imidazolyl or triazolyl, each optionally substituted with
up to 2
substituents independently selected from R11a on carbon atom ring members;
5 each R10b is independently halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2
alkoxy or C2-C4
alkoxycarbonyl;
G is G-1, G-3, G-12 or G-22;
xis 1 or 2;
each R13 is independently C(=0)NR14aRl4b or _u_v_Q; or C2-05 alkoxycarbonyl,
C3-05
10 alkenyloxycarbonyl, C3-05 alkynyloxycarbonyl or C4-C6
cycloalkoxycarbonyl, each
optionally substituted with up to 3 substituents independently selected from
R19;
each R14a is independently H or C1-C2 alkyl;
each R14b is independently H, C1-C3 alkyl, C1-C3 haloalkyl, cyclopropylmethyl
or C2-C4
alkoxyalkyl;
15 each R19 is independently cyano, halogen, cyclopropyl, cyclobutyl,
methoxy, halomethoxy
or methoxycarbonyl;
each U is independently a direct bond or C(=0)0;
each V is independently a direct bond or CH2;
each Q is independently phenyl or pyridinyl, each optionally substituted with
up to 2
20 substituents independently selected from R27;
each R27 is independently halogen, methyl or methoxy; and
Z is a direct bond, 0, NH, C(=0), C(=0)NH or NHC(=0).
Embodiment BB. The composition of Embodiment B wherein in Formula 1,
L is a direct bond or CH2;
25 G is G-1 or G-12; and
Z is a direct bond.
Embodiment BBB. The composition of Embodiment B wherein in Formula 1,
Z is a direct bond.
Embodiment C. The composition of Embodiment B wherein in Formula 1,
30 R2a and R2b are each H; or
R2a and R2b are taken together with the atoms X and Y to which they are
attached to form a
5-membered saturated ring containing ring members, in addition to the atoms X
and
Y, selected from carbon atoms;
A2 is a direct bond;
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
81
R6a and R6b are each H;
R8 is F or Cl;
L is a direct bond, CH2 or CH2CH2;
El is C1-C2 alkoxy or C2-C3 alkoxycarbonyl, wherein each carbon atom is
optionally
substituted with up to 1 substituent selected from R10a;
R10a is pyrazolyl or imidazolyl, each optionally substituted with up to 2
substituents
independently selected from R11' on carbon atom ring members;
each R11' is independently methoxycarbonyl or ethoxycarbonyl;
G is G-1 and the 2-position of G-1 is connected to Z and the 4-position is
connected to R13;
or G is G-12 and the 1-position of G-12 is connected to Z and the 4-position
is
connected to R13; or G is G-12 and the 1-position of G-12 is connected to Z
and the
3-position is connected to R13;
xis 1;
R13 is C(=0)NR14aRl4b or _u_v_Q; or C2-05 alkoxycarbonyl, C3-05
alkynyloxycarbonyl
or C4-C6 cycloalkoxycarbonyl, each optionally substituted with up to 1
substituent
selected from R19;
R14a is H;
R14b is H, methyl or cyclopropylmethyl;
R19 is cyano, halogen, cyclopropyl or methoxy;
U is C(=0)0;
V is CH2;
Q is phenyl optionally substituted with up to 2 substituents independently
selected from
R27; and
Z is a direct bond, 0, NH or C(=0).
Embodiment CC. The composition of Embodiment C wherein in Formula 1,
L is a direct bond or CH2; and
Z is a direct bond.
Embodiment D. The composition of Embodiment C wherein in Formula 1,
R8 is F;
L is a direct bond or CH2;
El is methoxy substituted with 1 substituent selected from R10a;
R10a is pyrazolyl optionally substituted with up to 1 substituent selected
from R11' on a
carbon atom ring member;
G is G-12 and the 1-position of G-12 is connected to Z and the 4-position is
connected to
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
82
R13; or G is G-12 and the 1-position of G-12 is connected to Z and the 3-
position is
connected to R13; and
R13 is C2-05 alkoxycarbonyl optionally substituted with up to 1 substituent
selected from
R19;
R19 is cyano, Cl, F, cyclopropyl or methoxy; and
Z is a direct bond.
Embodiment DD. The composition of Embodiment D wherein in Formula 1,
L is a direct bond or CH2, provided that when L is a direct bond, then E is
El, and when L
is CH2, then E is E2.
Embodiment E. The composition of Embodiment D wherein in Formula 1,
J is J-1;
q is 0;
L is CH2;
E is E2;
G is G-12 and the 1-position of G-12 is connected to Z and the 4-position is
connected to
R13; and
R13 is methoxycarbonyl or ethoxycarbonyl.
Embodiment EE. The composition of Embodiment E wherein in Formula 1,
R2a and R2b are taken together with the atoms X and Y to which they are
attached to form a
5-membered saturated ring containing ring members, in addition to the atoms X
and
Y, selected from carbon atoms.
Embodiment F. The composition of any one of Embodiments A through EE wherein
in
Formula 1,
T is T-2; and
R13 is ethoxycarbonyl.
Embodiment G. The composition of any one of Embodiments A through E wherein in
Formula
1,
T is T-3; and
R13 is ethoxycarbonyl.
Embodiment H. The composition any one of Embodiments A through G wherein
component (a)
comprises a compound selected from the group consisting of: Compound 1,
Compound 32,
Compound 64, Compound 71, Compound 126, Compound 127, Compound 132, Compound
162, Compound 163, Compound 171, Compound 186, Compound 218, Compound 221,
Compound 229, Compound 231, Compound 262, Compound 263, Compound 265,
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
83
Compound 297, Compound 330, Compound 331 and Compound 364.
Embodiment I. The composition of Embodiment H wherein component (a) comprises
a
compound selected from the group consisting of: Compound 32, Compound 64,
Compound
71, Compound 126, Compound 127, Compound 132, Compound 162, Compound 163,
Compound 171, Compound 186, Compound 218, Compound 229, Compound 263,
Compound 297, Compound 330 and Compound 331.
Embodiment J. The composition of Embodiment I wherein component (a) comprises
a
Compound 32.
Embodiment K. The composition of Embodiment I wherein component (a) comprises
Compound 64.
Embodiment Bl. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (Ill)
methyl
benzimidazole carbamate fungicides such as benomyl, carbendazim, fuberidazole
thiabendazole, thiophanate and thiophanate-methyl.
Embodiment B2. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b2)
dicarboximide
fungicides such as chlozolinate, dimethachlone, iprodione, procymidone and
vinclozolin.
Embodiment B3. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b3)
demethylation
inhibitor fungicides such as triforine, buthiobate, pyrifenox, pyrisoxazole
fenarimol,
nuarimol, triarimol econazole, imazalil, oxpoconazole, pefurazoate,
prochloraz,
triflumizoleazaconazole, bitertanol, bromuconazole, cyproconazole,
difenoconazole,
diniconazole (including diniconazole-M), epoxiconazole, etaconazole,
fenbuconazole,
fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole,
ipconazole,
mefentrifluconazole, metconazole, myclobutanil, penconazole, propiconazole,
ipfentrifluconazole, quinconazole, simeconazole, tebuconazole, tetraconazole
triadimefon,
triadimenol, triticonazole, uniconazole and uniconazole-P.
Embodiment B4. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b4)
phenylamide
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
84
fungicides such as metalaxyl, metalaxyl-M, benalaxyl, benalaxyl-M, furalaxyl,
ofurace and
oxadixyl.
Embodiment B5. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b5)
amine/morpholine fungicides such as aldimorph, dodemorph, fenpropimorph,
tridemorph,
trimorphamide, fenpropidin, piperalin and spiroxamine.
Embodiment B6. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b6)
phospholipid
biosynthesis inhibitor fungicides such as edifenphos, iprobenfos, pyrazophos
and
isoprothiolane.
Embodiment B7. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b7)
succinate
dehydrogenase inhibitor fungicides such as benodanil, flutolanil, mepronil,
isofetamid,
fluopyram, fenfuram, carboxin, oxycarboxin thifluzamide, benzovindiflupyr,
bixafen,
fluindapyr, fluxapyroxad, furametpyr, inpyrfluxam, isopyrazam, penflufen,
penthiopyrad,
pyrapropoyne, sedaxane, flubeneteram, isoflucypram, pydiflumetofen, boscalid
and
pyraziflumid.
Embodiment B8. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b8)
hydroxy(2-
amino-)pyrimidine fungicides such as bupirimate, dimethirimol and ethirimol.
Embodiment B9. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b9)
anilinopyrimidine fungicides such as cyprodinil, mepanipyrim and pyrimethanil.
Embodiment B10. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b10) N-
phenyl
carbamate fungicides such as diethofencarb.
Embodiment B11. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
wherein component (b) includes at least one compound selected from (1111)
fungicides
quinone outside inhibitor fungicides such as azoxystrobin, coumoxystrobin,
enoxastrobin,
flufenoxystrobin, picoxystrobin, pyraoxystrobin, mandestrobin, pyraclostrobin,
pyrametostrobin, triclopyricarb, kresoxim-methyl, trifloxystrobin,
dimoxystrobin,
5 fenaminstrobin, metominostrobin, orysastrobin, fluoxastrobin, famoxadone,
fenamidone
and pyribencarb.
Embodiment B12. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b12)
phenylpyrrole
10 fungicides compound such as fenpiclonil and fludioxonil.
Embodiment B13. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b13)
azanaphthalene
fungicides such as quinoxyfen and proquinazid.
15 Embodiment B14. The composition described in the Summary of the
Invention (including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b14) cell
peroxidation inhibitor fungicides such as biphenyl, chloroneb, dicloran,
quintozene,
tecnazene, tolclofos-methyl and etridiazole.
20 Embodiment B15. The composition described in the Summary of the
Invention (including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b15)
melanin
biosynthesis inhibitors-reductase fungicides such as fthalide, pyroquilon and
tricyclazole.
Embodiment B16a. The composition described in the Summary of the Invention
(including but
25 not limited to the composition of any one of Embodiments 1 through 258
and A through K)
wherein component (b) includes at least one compound selected from (b16a)
melanin
biosynthesis inhibitors-dehydratase fungicides such as carpropamid,
diclocymet, and
fenoxanil.
Embodiment B16b. The composition described in the Summary of the Invention
(including but
30 not limited to the composition of any one of Embodiments 1 through 258
and A through K)
wherein component (b) includes at least one compound selected from (b16b)
melanin
biosynthesis inhibitor-polyketide synthase fungicides such as tolprocarb.
Embodiment B17. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
86
wherein component (b) includes at least one compound selected from (b17) keto
reductase
inhibitor fungicides such as fenhexamid, fenpyrazamine, quinofumelin and
ipflufenoquin.
Embodiment B18. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b18)
squalene-
epoxidase inhibitor fungicides such as pyributicarb, naftifine and
terbinafine.
Embodiment B19. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b19)
polyoxin
fungicides such as polyoxin.
Embodiment B20. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 243 and A
through K)
wherein component (b) includes at least one compound selected from (b20)
phenylurea
fungicides such as pencycuron.
Embodiment B21. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b21)
quinone inside
inhibitor fungicides such as cyazofamid, amisulbrom and fenpicoxamid (Registry
Number
517875-34-2).
.. Embodiment B22. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b22)
benzamide and
thiazole carboxamide fungicides such as zoxamide and ethaboxam.
Embodiment B23. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b23)
enopyranuronic
acid antibiotic fungicides such as blasticidin-S.
Embodiment B24. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b24)
hexopyranosyl
antibiotic fungicides such as kasugamycin.
Embodiment B25. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b25)
glucopyranosyl
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
87
antibiotic: protein synthesis fungicides such as streptomycin.
Embodiment B26. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b26)
glucopyranosyl
antibiotic: trehalase and inositol biosynthesis fungicides such as
validamycin.
Embodiment B27. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b27)
cyanoacetylamideoxime fungicides such as cymoxanil.
Embodiment B28. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b28)
carbamate
fungicides such as propamacarb, prothiocarb and iodocarb.
Embodiment B29. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b29)
oxidative
phosphorylation uncoupling fungicides such as fluazinam, binapacryl,
meptyldinocap and
dinocap.
Embodiment B30. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b30)
organo tin
fungicides such as fentin acetate, fentin chloride and fentin hydroxide.
Embodiment B31. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b31)
carboxylic acid
fungicides such as oxolinic acid.
Embodiment B32. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b32)
heteroaromatic
fungicides such as hymexazole and octhilinone.
Embodiment B33. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b33)
phosphonate
fungicides such as phosphorous acid and its various salts, including fosetyl-
aluminum.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
88
Embodiment B34. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b34)
phthalamic acid
fungicides such as teclofthalam.
Embodiment B35. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b35)
benzotriazine
fungicides such as triazoxide.
Embodiment B36. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b36)
benzene-
sulfonamide fungicides such as flusulfamide.
Embodiment B37. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b37)
pyridazinone
fungicides such as diclomezine.
Embodiment B38. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b38)
thiophene-
carboxamide fungicides such as silthiofam.
Embodiment B39. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b39)
complex I
NADH oxidoreductase inhibitor fungicides such as diflumetorim, tolfenpyrad and
fenazaquin.
Embodiment B40. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b40)
carboxylic acid
amide fungicides such as dimethomorph, benthiavalicarb, benthiavalicarb-
isopropyl,
iprovalicarb, valifenalate, mandipropamid, flumorph, dimethomorph, flumorph,
pyrimorph,
benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb, tolprocarb,
valifenalate and
mandipropamid.
Embodiment B41. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
89
wherein component (b) includes at least one compound selected from (b41)
tetracycline
antibiotic fungicides such as oxytetracycline.
Embodiment B42. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b42)
thiocarbamate
fungicides such as methasulfocarb.
Embodiment B43. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b43)
benzamide
fungicides such as fluopicolide and fluopimomide.
Embodiment B44. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b44)
microbial
fungicides such as Bacillus arnyloliquefaciens strains Q5T713, FZB24, MB1600,
D747,
F727, TJ100 (also called strain 1 BE; known from EP2962568) and the fungicidal
lipopeptides which they produce.
Embodiment B45. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b45)
quinone outside
inhibitor, stigmatellin binding fungicides such as ametoctradin.
Embodiment B46. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b46) plant
extract
fungicides such as Melaleuca altemifolia, eugenol, geraniol and thymol.
Embodiment B47. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b47)
cyanoacrylate
fungicides such as phenamacril.
Embodiment B48. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b48)
polyene
fungicides such as natamycin.
Embodiment B49. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
wherein component (b) includes at least one compound selected from (b49)
oxysterol
binding protein inhibitor fungicides such as oxathiapiprolin and
fluoxapiprolin.
Embodiment B50. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
5 wherein component (b) includes at least one compound selected from (b50)
aryl-phenyl-
ketone fungicides such as metrafenone and pyriofenone.
Embodiment B51. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b51) host
plant
10 defense induction fungicides such as acibenzolar-S-methyl, probenazole,
tiadinil, isotianil,
laminarin, extract from Reynoutria sachalinensis and Bacillus rnycoides
isolate J and cell
walls of Saccharornyces cerevisiae strain LAS117.
Embodiment B52. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
15 wherein component (b) includes at least one compound selected from (b52)
multi-site
activity fungicides such as copper oxychloride, copper sulfate, copper
hydroxide, Bordeaux
composition (tribasic copper sulfide), elemental sulfur, ferbam, mancozeb,
maneb, metiram,
propineb, thiram, zinc thiazole, zineb, ziram, folpet, captan, captafol,
chlorothalonil,
dichlofluanid, tolyfluanid, guazatine, iminoctadine albesilate, iminoctadine
triacetate,
20 anilazine, dithianon, quinomethionate and fluoroimide.
Embodiment B53. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b53)
biological
fungicides with multiple modes of action such as extract from the cotyledons
of lupine
25 plantlets.
Embodiment B54. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b54)
fungicides other
than fungicides of component (a) and components (bl) through (b53), such as
30 cyflufenamid, bethoxazin, neo-asozin, pyrrolnitrin, tebufloquin, dodine,
flutianil, ferimzone,
picarbutrazox, dichlobentiazox (Registry Number 957144-77-3), dipymetitrone
(Registry
Number 16114-35-5), flometoquin, tolnifanide (Registry Number 304911-98-6), N-
[4-[4-
chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyll-N-ethyl-N-
methylmethanimid-
amide, 5-fluoro-2-[(4-fluorophenyl)methoxy]-4-pyrimidinamine and 4-
fluorophenyl N-[1-
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
91
[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate (XR-539).
Embodiment B55. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes (1S)-2,2-bis(4-fluoropheny1)-1-methylethyl N-[
[3-
(acetyloxy)-4-methoxy-2-pyridinyl]carbony1]-L-alaninate (provisional common
name
florylpicoxamid).
Embodiment B56. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes 1-[2-[[[1-(4-chloropheny1)-1H-pyrazol-3-
yl]oxylmethyl]-
3-methylpheny1]-1,4-dihydro-4-methy1-5H-tetrazol-5-one (provisional common
name
metyltetraprole).
Embodiment B57. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes 3-chloro-4-(2,6-difluoropheny1)-6-methy1-5-
phenylpyridazine (provisional common name pyridachlometyl).
Embodiment B58. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes (4-phenoxyphenyl)methyl 2-amino-6-methyl-
pyridine-3-
carboxylate (provisional common name aminopyrifen).
Embodiment B59. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b54.11)
(i.e Formula
b54.11)
H3C
Rb10
u
Rb13
0
b54.11
Rbll
wherein
Rb10 and Rb11 are each independently halogen; and
R6 is H, halogen, C1-C3 alkyl, C1-C3 haloalkyl or C3-C6 cycloalkyl.
Embodiment B60. The composition of Embodiment B59 wherein component (b)
includes at
least one fungicidal compound selected from the group consisting of methyl
N4[541-(2,6-
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
92
difluoro-4-formylpheny1)-1H-pyrazol-3-y1]-2-methylphenyl] methyl]carbamate,
methyl N-
[[5-[1-(4-cyclopropy1-2,6-dichloropheny1)-1H-pyrazol-3-y1]-2-
methylphenyl]methy1]-
carbamate, methyl N-[[5-[1-(4-chloro-2,6-difluoropheny1)-1H-pyrazol-3-y1]-2-
methyl-
phenyl]methyl]carbamate, methyl N- [[5-[1-(4-cyclopropy1-2,6-difluoropheny1)-
1H-pyrazol-
3-y1]-2-methylphenyl]methyl]carbamate, methyl N-[[5-[1-[2,6-difluoro-4-(1-
methylethyl)
pheny1]-1H-pyrazol-3-y1]-2-methylphenyl]methyl]carbamate and methyl N-[[5-[1-
[2,6-di
fluoro-4-(trifluoromethyl)pheny1]-1H-pyrazol-3-y1]-2-
methylphenyl]methyl]carbamate.
Embodiment B61. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b54.12)
(i.e Formula
b54.12)
Rb5
04
b54.12
wherein
Rb4 is
Rb6
NN
Rb6 or
0
Rb6 is C2-C4 alkoxycarbonyl or C2-C4 haloalkylaminocarbonyl;
L is CH2 or CH20, wherein the atom to the right is connected to the phenyl
ring in Formula
b54.12; and
Rb5 is
0
)----CF3
Embodiment B62. The composition of Embodiment B61 wherein component (b)
includes at
least one fungicidal compound selected from the group consisting of N-(2,2,2-
trifluoroethyl)-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methy1]-
4-
oxazolecarboxamide and ethyl 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-
yl]phenoxy]
methy1]-1H-pyrazole-4-carboxylate.
Embodiment B63. The composition described in the Summary of the Invention
(including but
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
93
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one compound selected from (b54.13)
(i.e Formula
b54.13)
Rb8
411 Rb7
Rb 1 0 D b9 CH3
b 1 1
R \\T
C
NO2 H3
b54.13
wherein
Rb7, Rb8 and Rb9 are each independently H, halogen or cyano; and
Rb10 and Rbll are each independently H, halogen, C1-C3 alkyl or C1-C3 methoxy
Embodiment B64. The composition of Embodiment B63 wherein component (b)
includes at
least one fungicidal compound selected from the group consisting of 4-(2-
chloro-4-
fluoropheny1)-N-(2-fluoro-4-methyl-6-nitropheny1)-1,3-dimethyl-1H-pyrazol-5-
amine, 4-(2-
chloro-4-fluoropheny1)-N-(2-fluoro-6-nitropheny1)-1,3-dimethyl-1H-pyrazol-5-
amine, 3,5-
difluoro-4-[5-[(4-methoxy-2-nitrophenyl)amino]-1,3-dimethy1-1H-pyrazol-4-y11-
benzonitrile and N-(2-chloro-4-fluoro-6-nitropheny1)-4-(2-chloro-4-
fluoropheny1)-1,3-
dimethyl-1H-pyrazol-5-amine.
.. Embodiment B65. The composition described in the Summary of the Invention
(including but
not limited to the composition of any one of Embodiments 1 through 258 and A
through K)
wherein component (b) includes at least one fungicidal compound (fungicide)
selected from
the group consisting of azoxystrobin, benzovindiflupyr, boscalid (nicobifen),
bixafen,
bromuconazole, carbendazim, chlorothalonil, copper hydroxide, cyflufenamid,
cyproconazole, difenoconazole, dimoxystrobin, epoxiconazole, famoxadone,
fenbuconazole, fenpropidin, fenpropimorph, fluindapyr, flusilazole,
flutriafol, fluxapyroxad,
hexaconazole, ipconazole kresoxim-methyl, manzate, metconazole,
metominostrobin,
metrafenone, myclobutanil, penconazole, penthiopyrad, picoxystrobin,
prochloraz,
propiconazole, proquinazid, prothioconazole, pydiflumetofen, pyraclostrobin,
pyrametostrobin, pyraoxystrobin, pyriofenone quinoxyfen, tebuconazole,
trifloxystrobin,
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
94
triticonazole, methyl N-[[5-[1- [2,6-difluoro-4-(1-methylethyl)pheny1]-1H-
pyrazol-3-y1]-2-
methylphenyl]methyl]carbamate, methyl N- [[5-[1-[2,6-difluoro-4-
(trifluoromethyl)pheny1]-
1H-pyrazol-3-y1]-2-methylphenyl]methyl]carbamate, N-(2,2,2-trifluoroethyl)-2-
[[4-[5-
(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methy1]-4-oxazolecarboxamide,
ethyl 1-[[4-
[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenoxy]methy1]-1H-pyrazole-4-
carboxylate, 4-
(2-chloro-4-fluoropheny1)-N-(2-fluoro-4-methy1-6-nitropheny1)-1,3-dimethyl-1H-
pyrazol-5-
amine, 4-(2-chloro-4-fluoropheny1)-N-(2-fluoro-6-nitropheny1)-1,3-dimethyl-1H-
pyrazol-5-
amine and 3,5-difluoro-4-[5-[(4-methoxy-2-nitrophenyl)amino]-1,3-dimethy1-1H-
pyrazol-
4-y1]-benzonitrile.
Embodiment B66. The composition of Embodiment B65 wherein component (b)
includes at
least one compound selected from the group consisting of azoxystrobin,
benzovindiflupyr,
bixafen, chlorothalonil, copper hydroxide, cyflufenamid, cyproconazole,
difenoconazole,
dimoxystrobin, epoxiconazole, famoxadone, fenpropidin, fenpropimorph,
fluindapyr,
flusilazole, flutriafol, fluxapyroxad, kresoxim-methyl, manzate, metconazole,
metominostrobin, metrafenone, myclobutanil, penthiopyrad, picoxystrobin,
propiconazole,
proquinazid, prothioconazole, pydiflumetofen, pyraclostrobin, pyrametostrobin,
pyraoxystrobin, pyriofenone, quinoxyfen, tebuconazole, trifloxystrobin,
triticonazole,
methyl N- [[5-[1-[2,6-difluoro-4-(1-methylethyl)pheny1]-1H-pyrazol-3-y1]-2-
methylphenyl]
methyl]carbamate, methyl N- [[5-[1-[2,6-difluoro-4-(trifluoromethyl)pheny1]-1H-
pyrazol-3-
y1]-2-methylphenyl]methyl]carbamate, N-(2,2,2-trifluoroethyl)-2-[[4-[5-
(trifluoromethyl)-1,
2,4-oxadiazol-3-yl]phenyl]methy1]-4-oxazolecarboxamide, ethyl 1-[[4-[5-
(trifluoromethyl)-
1,2,4-oxadiazol-3-yl]phenoxy]methy1]-1H-pyrazole-4-carboxylate, 4-(2-chloro-4-
fluoropheny1)-N-(2-fluoro-4-methy1-6-nitropheny1)-1,3-dimethyl-1H-pyrazol-5-
amine, 4-(2-
chloro-4-fluoropheny1)-N-(2-fluoro-6-nitropheny1)-1,3-dimethyl-1H-pyrazol-5-
amine and 3,
5-difluoro-4-[5-[(4-methoxy-2-nitrophenyl)amino]-1,3-dimethy1-1H-pyrazol-4-y1]-
benzonitrile.
Embodiment B67. The composition of Embodiment B66 wherein component (b)
includes at
least one compound selected from the group consisting of azoxystrobin,
benzovindiflupyr,
bixafen, chlorothalonil, copper hydroxide, cyproconazole, difenoconazole,
epoxiconazole,
fenpropidin, fenpropimorph, fluindapyr, flutriafol, fluxapyroxad, manzate,
metominostrobin, picoxystrobin, prothioconazole, pydiflumetofen,
pyraclostrobin,
tebuconazole, trifloxystrobin, methyl N- [[5-[1-[2,6-difluoro-4-(1-
methylethyl)pheny1]-1H-
pyrazol-3-y1]-2-methylphenyl]methyl]carbamate, methyl N-[[5-[1-[2,6-difluoro-4-
(trifluoromethyl)pheny1]-1H-pyrazol-3-y1]-2-methylphenyl]methyl]carbamate, N-
(2,2,2-
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
trifluoroethyl)-2- [ [4- [5 -(trifluoromethyl)- 1,2,4-ox adiazol-3 -yl]phenyl]
methyl] -4-
oxazolecarboxamide, ethyl 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-
yl]phenoxy]
methy1]-1H-pyrazole-4-carboxylate, 4-(2-chloro-4-fluoropheny1)-N-(2-fluoro-4-
methy1-6-
nitropheny1)-1,3 -dimethy1-1H-pyrazol-5- amine, 4-(2-chloro-4 -fluoropheny1)-N-
(2-fluoro-6-
5 nitropheny1)-1,3 -dimethy1-1H-pyrazol-5- amine and 3 ,5-difluoro-4- [5-
[(4 -methoxy-2-
nitrophenyl)amino] -1,3 -dimethyl- 1H-pyrazol-4-yl] -benzonitrile.
Embodiment B68. The composition of Embodiment B67 wherein component (b)
includes at
least one compound selected from the group consisting of azoxystrobin,
benzovindiflupyr,
bixafen, chlorothalonil, copper hydroxide, cyproconazole, epoxiconazole,
fenpropidin,
10 fenpropimorph, fluindapyr, flutriafol, fluxapyroxad, manzate,
metominostrobin,
picoxystrobin, prothioconazole, pydiflumetofen, pyraclostrobin, tebuconazole,
trifloxystrobin.
Of note is the composition of any one of the embodiments described herein,
including any
Embodiments 1 through 258, A through K, and B1 through B68, wherein reference
to Formula 1
15
includes salts thereof but not N-oxides thereof; therefore the phrase "a
compound of Formula 1"
can be replaced by the phrase "a compound of Formula 1 or a salt thereof'. In
this composition
of note, component (a) comprises a compound of Formula 1 or a salt thereof.
Also noteworthy as embodiments are fungicidal compositions of the present
invention
comprising a fungicidally effective amount of a composition of Embodiments 1
through 258, A
20
through K, and B1 through B68, and at least one additional component selected
from the group
consisting of surfactants, solid diluents and liquid diluents.
Embodiments of the invention further include methods for controlling plant
diseases caused
by fungal plant pathogens comprising applying to the plant or portion thereof,
or to the plant seed
or seedling, a fungicidally effective amount of a composition any one of
Embodiments 1 through
25
258, A through K, and B1 through B68 (e.g., as a composition including
formulation ingredients
as described herein). Embodiments of the invention also include methods for
protecting a plant
or plant seed from diseases caused by fungal pathogens comprising applying a
fungicidally
effective amount of a composition of any one of Embodiments 1 through 258, A
through K, and
B1 through B68 to the plant or plant seed.
30
Some embodiments of the invention involve control of a plant disease or
protection from a
plant disease that primarily afflicts plant foliage and/or applying the
composition of the invention
to plant foliage (i.e. plants instead of seeds). The preferred methods of use
include those involving
the above preferred compositions; and the diseases controlled with particular
effectiveness include
plant diseases caused by fungal plant pathogens. Combinations of fungicides
used in accordance
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
96
with this invention can facilitate disease control and retard resistance
development.
Method embodiments further include:
Embodiment Cl. A method for protecting a plant from a disease selected from
rust,
powdery mildew and Sep toria diseases comprising applying to the plant a
fungicidally effective amount of the composition comprising components (a) and
(b)
described in the Summary of the Invention or any one of Embodiments 1 through
258.
Embodiment C2. The method of Embodiment Cl wherein the disease is a rust
disease and
component (b) of the composition includes at least one fungicidal compound
selected from (b3) demethylation inhibitor (DMI) fungicides, (b5)
amine/morpholine
fungicides, (b7) succinate dehydrogenase inhibitor fungicides, (1111) quinone
outside
inhibitor (QoI) fungicides, (b13) methyl benzimidazole carbamate fungicides
and
(b52) multi-site activity fungicides.
Embodiment C3. The method of Embodiment C2 wherein component (b) of the
composition includes at least one fungicidal compound selected from (b3)
demethylation inhibitor (DMI) fungicides, (b7) succinate dehydrogenase
inhibitor
fungicides and (b11) quinone outside inhibitor (QoI) fungicides.
Embodiment C4. The method of Embodiment C3 wherein component (b) of the
composition includes at least one fungicidal compound selected from the group
consisting of azoxystrobin, cyproconazole, difenoconazole, epoxiconazole,
fluindapyr, flutriafol, fluxapyroxad, picoxystrobin, prothioconazole,
pyraclostrobin,
tebuconazole and trifloxystrobin.
Embodiment C5. The method of Embodiments C2 through C4 wherein the disease is
Asian
soybean rust caused by Puccinia recondite.
Embodiment C6. The method of Embodiments C2 through C4 wherein the disease is
wheat
leaf rust caused by Phakopsora pachyrhizi.
Embodiment C7. The method of Embodiment Cl wherein the disease is a powdery
mildew
disease and component (b) of the composition includes at least one fungicidal
compound selected from (b3) demethylation inhibitor (DMI) fungicides, (b11)
quinine outside inhibitor (QoI) fungicides and (b13) azanaphthalene
fungicides.
Embodiment C8. The method of Embodiment C7 wherein the disease is wheat
powdery
mildew.
Embodiment C9. The method of Embodiment C7 wherein the disease is grape downy
mildew.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
97
Embodiment C10. The method of Embodiments C7 through C9 wherein component (b)
includes at least one fungicidal compound selected from (b3) DMI fungicides.
Embodiment C11. The method of Embodiment C10 wherein component (b) includes at
least one fungicidal compound selected from the group consisting of
cyproconazole,
difenoconazole, epoxiconazole, prothioconazole and tebuconazole.
Embodiment C12. The method of Embodiment C11 wherein component (b) includes at
least one fungicidal compound selected from the group consisting of
cyproconazole,
difenoconazole and prothioconazole.
Embodiment C13. The method of Embodiments C8 through C10 wherein component (b)
includes at least one fungicidal compound selected from (b11) QoI fungicides.
Embodiment C14. The method of Embodiment C12 wherein component (b) includes at
least one fungicidal compound selected from the group consisting of
azoxystrobin,
picoxystrobin and pyraclostrobin.
Embodiment C15. The method of Embodiment Cl wherein the disease is a Septoria
disease and component (b) of the composition includes at least one fungicidal
compound selected from the group consisting of epoxiconazole, metalaxyl
(including metalaxyl-M), iprovalicarb and fenpropimorph.
Embodiment C16. The method of Embodiment C15 wherein the disease is wheat leaf
blotch.
Embodiment C17. The method of any one of Embodiments Cl through C16 wherein
components (a) and (b) are applied in synergistically effective amounts (and
in a
synergistic ratio relative to each other).
Of note are embodiments that are counterparts of Embodiments Cl through C17
relating to
a method for controlling plant diseases caused by fungal plant pathogens
comprising applying to
the plant or portion thereof, a fungicidally effective amount of a fungicidal
composition of the
invention.
As noted in the Summary of the Invention, this invention also relates to a
compound of
Formula 1, or an N-oxide or salt thereof. Also noted is that the embodiments
of this invention,
including Embodiments 1-258, relate also to compounds of Formula 1.
Accordingly,
combinations of Embodiments 1-258 are further illustrated by:
Embodiment Dl. A compound of Formula 1, or an N-oxide or salt thereof, wherein
T is T-2;
R1 is CF3;
Xis 0;
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
98
Y is 0;
R2a is H or methyl;
R2b is C3-C15 trialkylsilyl or C3-C15 halotrialkylsilyl;
Al is 0;
A2 is a direct bond or CH2;
R6a and R6b are each independently H, cyano hydroxy or methyl;
J is J-1 or J-6;
q is 0 or 1;
L is a direct bond or CH2;
E is El or E2;
El is C1-C3 alkoxy, C2-C3 alkylcarbonyl or C2-C3 alkoxycarbonyl, wherein each
carbon
atom is optionally substituted with up to 1 substituent selected from R113a
and up to 3
substituents independently selected from R10b;
R10a is pyrazolyl, imidazolyl or triazolyl, each optionally substituted with
up to 2
substituents independently selected from R11' on carbon atom ring members;
each RlOb is independently halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy
or C2-C4
alkoxycarbonyl;
each R11' is independently methoxycarbonyl or ethoxycarbonyl;
G is G-1, G-3, G-12 or G-22;
x is 1 or 2;
each R13 is independently C(=0)NR14aRl4b or _u_v_Q; or C2-05 alkoxycarbonyl,
C3-05
alkenyloxycarbonyl, C3-05 alkynyloxycarbonyl or C4-C6 cycloalkoxycarbonyl,
each
optionally substituted with up to 3 substituents independently selected from
R19;
each R14a is independently H or C1-C2 alkyl;
each R14b is independently H, C1-C3 alkyl, C1-C3 haloalkyl, cyclopropylmethyl
or C2-C4
alkoxyalkyl;
each R19 is independently cyano, halogen, cyclopropyl, cyclobutyl, methoxy,
halomethoxy
or methoxycarbonyl;
each U is independently a direct bond or C(=0)0;
each V is independently a direct bond or CH2;
each Q is independently phenyl or pyridinyl, each optionally substituted with
up to 2
substituents independently selected from R27;
each R27 is independently halogen, methyl or methoxy; and
Z is a direct bond, 0, NH, C(=0), C(=0)NH or NHC(=0).
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
99
Embodiment D2. A compound of Embodiment D1 wherein
R2a is H or methyl;
R2b is trimethylsilyl or halotrimethylsilyl;
A2 is a direct bond;
R6a and R6b are each H;
R8 is F or Cl;
El is C1-C2 alkoxy or C2-C3 alkoxycarbonyl, wherein each carbon atom is
optionally
substituted with up to 1 substituent selected from R10a;
R10a is pyrazolyl or imidazolyl, each optionally substituted with up to 2
substituents
independently selected from R11' on carbon atom ring members;
each R11' is independently methoxycarbonyl or ethoxycarbonyl;
G is G-1 and the 2-position of G-1 is connected to Z and the 4-position is
connected to R13;
or G is G-12 and the 1-position of G-12 is connected to Z and the 4-position
is
connected to R13; or G is G-12 and the 1-position of G-12 is connected to Z
and the
3-position is connected to R13;
xis 1;
R13 is C(=0)NR14aRl4b or _u_v_Q; or C2-05 alkoxycarbonyl, C3-05
alkynyloxycarbonyl
or C4-C6 cycloalkoxycarbonyl, each optionally substituted with up to 1
substituent
selected from R19;
104a is H;
R14b is H, methyl or cyclopropylmethyl;
R19 is cyano, halogen, cyclopropyl or methoxy;
U is C(=0)0;
V is CH2;
Q is phenyl optionally substituted with up to 2 substituents independently
selected from
R27; and
Z is a direct bond, 0, NH or C(=0).
Embodiment D3. A compound of Embodiment D2 wherein
R2a is H or methyl;
R2b is trimethylsilyl;
R8 is F;
El is methoxy substituted with 1 substituent selected from RiOa;
R10a is pyrazolyl optionally substituted with up to 1 substituent selected
from R11' on a
carbon atom ring member;
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
100
G is G-12 and the 1-position of G-12 is connected to Z and the 4-position is
connected to
R13; or G is G-12 and the 1-position of G-12 is connected to Z and the 3-
position is
connected to R13; and
R13 is C2-05 alkoxycarbonyl optionally substituted with up to 1 substituent
selected from
R19;
R19 is cyano, Cl, F, cyclopropyl or methoxy; and
Z is a direct bond.
Embodiment D3. A compound of Embodiment D3 wherein
R2a is methyl;
J is J-1;
q is 0;
L is CH2;
E is E2;
G is G-12 and the 1-position of G-12 is connected to Z and the 4-position is
connected to
R13; and
R13 is methoxycarbonyl or ethoxycarbonyl.
Additional embodiments include a fungicidal composition comprising: (1) a
compound of
any one of Embodiments D1 through D3; and (2) at least one additional
component selected from
the group consisting of surfactants, solid diluents and liquid diluents.
Additional embodiments
also include a method for protecting a plant or plant seed from diseases
caused by fungal
pathogens comprising applying a fungicidally effective amount of the compound
of any one of
Embodiments D1 through D3 to the plant (or portion thereof) or plant seed
(directly or through
the environment (e.g., growing medium) of the plant or plant seed). Of note
are embodiments
relating to a method for controlling plant diseases caused by fungal plant
pathogens comprising
applying to the plant or portion thereof, a fungicidally effective amount of a
compound of any one
of Embodiments D1 through D3.
This invention also provides a fungicidal composition comprising a compound of
Formula
1 (including all stereoisomers, N-oxides, and salts thereof) (i.e. in a
fungicidally effective amount),
and at least one additional component selected from the group consisting of
surfactants, solid
diluents and liquid diluents. Of note as embodiments of such compositions are
compositions
comprising a compound corresponding to any of the compound embodiments
described above.
One or more of the following methods and variations as described in Schemes 1-
17 can be
used to prepare the compounds of Formula 1. The definitions of E, L, A, A1,
A2, J, T, X, Y, R1,
R2a, R2b, R2c, R2d, R6a, R6b and R29 in the compounds of Formulae 1-14 below
are as defined
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
101
above in the Summary of the Invention unless otherwise noted. Compounds of
Formulae la-lal,
lb-lb6 and lc-lci are various subsets of Formula 1, and all substituents for
Formulae la-lal, lb-
1b6 and lc-lci are as defined above for Formula 1 unless otherwise noted. As
the synthetic
literature includes many halomethyl ketone and hydrate-forming methods, which
can readily be
adapted to prepare compounds of the present invention, the following methods
in Schemes 1-17
are simply representative examples of a wide variety of procedures useful for
the preparation of
the compounds of Formula 1. For reviews of ketone and hydrate-forming methods,
see, for
example, Tetrahedron 1991, 47, 3207-3258 and Chem. Communications 2013,
49(95), 11133-
11148, and references cited therein. Also see the methods outlined in U.S.
Patent 6,350,892.
As shown in Scheme 1, Compounds of Formula la (i.e. Formula 1 wherein T is T-1
and
W is 0) wherein R1 is CF3 can be prepared by trifluoroacetylation of
organometallic compounds
of Formula 2. Typically, the ethyl ester of trifluoroacetic acid (i.e. ethyl
trifluoroacetate) is used
as the source of the trifluoroacetyl group in this method, but
trifluoroacetonitrile and various
trifluoroacetate salts can also be used. Depending on the reaction conditions,
double-addition on
the trifluoroacetyl compound can occur. Conducting the reaction at ¨65 C, or
more preferably
at ¨78 C, can reduce the occurrence of double addition adducts to trace
amounts, particularly
when using organometallic species of Formula 2 wherein M is Li or MgBr. Many
other
organometallic species yield similar results. For reaction conditions useful
in the method of
Scheme 1, as well as other well-established routes for the synthesize
trifluoromethyl ketones see,
for example, Journal of Organic Chemistry 1987, 52(22), 5026-5030; Chemical
Communications
2013, 49(95), 11133-11148; and Journal of Fluorine Chemistry 1981, 18, 117-
129. Conditions
described in these references can easily be modified to prepare compounds of
Formula la wherein
R1 is other than CF3 (e.g., dihalo- or trichloro-moieties).
Scheme 1
Et0R1 0
E M E )\
A A
1 i wherein R s CF3
2 la
M is, e.g., Li, Na, K, Cs or MgBr wherein R1 is CF3
Compounds of Formula la (i.e. Formula 1 wherein T is T-1 and W is 0) wherein
R1 is
CF3 can also be prepared via alkylation of ethyl 4,4,4-trifluoroacetoacetate
(ETFAA) with
compounds of Formula 3 wherein La is a leaving group such as halogen (e.g.,
Cl, Br) or sulfonate
(e.g., mesylate). In this method ETFAA is first treated with a base such as
sodium hydride in a
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
102
polar aprotic solvent such tetrahydrofuran (THF), THF/hexamethylphosphoramide
(HMPA) or
acetone. The ETFAA anion then displaces the leaving group in compounds of
Formula 3 to give
an intermediate ester which undergoes hydrolysis and decarboxylation in the
presence of lithium
chloride (LiC1) and N,N-dimethylformamide (DMF) to give the ketone compound of
Formula la.
For reaction conditions see Journal Chemical Society, Chemical Communications
1989, (2), 83-
84; Chemical Communications 2013, 49(95), 11133-11148; and Journal of Fluorine
Chemistry
1989, 44, 377-394.
Scheme 2
0 0 I. base (e.g., NaH) 0
E
Et0 R1 A
2. a
ETFAA A la
3
wherein R is CF3 3. LiCI, DMF wherein R1 is
CF3
La is a leaving group such as Cl, Br or 0Ms
As shown in Scheme 3, compounds of Formula la (i.e. Formula 1 wherein T is T-1
and W
is 0) wherein R1 is CF3 can also be prepared by trifluoromethylation of an
ester of Formula 5
with trifluoromethyltrimethylsilane (TMS-CF3). The reaction is run in the
present of a fluoride
initiator such as tetrabutylammonium fluoride, and in an anhydrous solvent
such as toluene or
dichloromethane at about ¨78 C (for reaction conditions see, for example,
Angew. Chem., Int.
Ed. 1998, 37(6), 820-821). Cesium fluoride can also be used as an initiator in
a solvent such as
1,2-dimethoxyethane (glyme) at room temperature (for reaction conditions see,
for example, J.
Org. Chem., 1999, 64, 2873). The reaction proceeds through a trimethylsilicate
intermediate,
which is hydrolyzed with aqueous acid to give the desired trifluoromethyl
ketone compound of
Formula la. Weinreb amides may also be used in place of the starting esters
(see, for example,
Chem. Commun. 2012, 48, 9610).
Scheme 3
0 0
TMS-CF3
J )L )L
A RI
3 ______________________________________________
A 0
5 la
wherein R1 is CF3
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
103
As shown in Scheme 4, compounds of Formula 1a1 (i.e. Formula la wherein A is
A1-A2-
cR6aR6b) wherein R1 is CF3 and at least one R6a or R6b is H can be prepared by
reacting acid
chlorides of Formula 6 with trifluoroacetic anhydride (TFAA) and pyridine in a
solvent such as
dichloromethane or toluene at a temperature between about 0 to 80 C followed
by aqueous
hydrolysis (for reaction conditions see, for example, Tetrahedron 1995, 51,
2573-2584).
Compounds of Formula 6 can be prepared from compounds of Formula 5 by ester
hydrolysis to
the corresponding carboxylic acid and treatment with oxalyl chloride, as known
to one skilled in
the art.
Scheme 4
0 0
TFAA A2)(L
1' E
A CI A R
pyridine
py
R6a R6b lal R6a R6b
6
wherein at least one R6a or R6b is H wherein R is CF3 and
at least one R6a or R61) is H
As shown in Scheme 5, compounds of Formula lb (i.e. Formula 1 wherein T is T-
2)
wherein R2aX and R2bY are OH can be prepared by oxidation of alcohols of
Formula 4 to the
corresponding dihydroxy. The oxidation reaction can be performed by a variety
of means, such
as by treatment of the alcohols of Formula 4 with manganese dioxide, Dess-
Martin periodinane,
pyridinium chlorochromate or pyridinium dichromate. For typical reaction
conditions, see present
Example 6, Step F and Example 8, Step F.
Scheme 5
RZX YR2b
OH
oxidation
ER1 /j\ X R1
A 0.= A
4 lb
wherein R2a X and R2bY are both OH
Scheme 6 illustrates a specific example of the general method of Scheme 5 for
the
preparation of a compound of Formula lb 1 (i.e. Formula lb wherein L is CH2, J
is phenyl (i.e.
J-1), A is OCH2 and R1 is CF3). In this method a compound of Formula 4a (i.e.
Formula 4
wherein L is CH2, J is phenyl (i.e. J-1), A is OCH2 and R1 is CF3) is reacted
with an oxidizing
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
104
reagent such as Des s-Martin periodinane in a solvent such as dichloromethane
at a temperature
between about 0 to 80 C. Present Example 1, Step C illustrates the method of
Scheme 6.
Scheme 6
R2a R2b
OH X Y
=
0)(Oj Dess-Martin periodinane
CF3
CF3
lbl
4a
wherein R2a X and R2bY are both OH
As shown in Scheme 7, compounds of Formula 4 can be prepared by reaction of
compounds of Formula 2 with R1CHO. For reactions conditions see, Tetrahedron
Letters 2007,
48, 6372-6376.
Scheme 7
OH
E J M RiCHO
A A
2 4
M is, e.g., Li, Na, K, Cs or MgBr
As shown in Scheme 8, compounds of Formula 4b (i.e. Formula 4 wherein A is
OcR6aR6b) can be prepared by reacting a compound of Formula 7 with an epoxide
of Formula 8.
The reaction is typically carried out in a solvent such as acetonitrile with a
catalytic amount of a
base such as cesium or potassium carbonate at a temperature between about 20
to 80 C; or in a
solvent such as dichloromethane with a catalytic amount of a Lewis acid such
as boron trifluoride
etherate at a temperature between about 0 to 40 C. Present Example 8, Step E
illustrates the
method of Scheme 8. One skilled in the art will recognize that the method of
Scheme 8 can also
be performed when A is SCR6aR6b or N(R7a)cR6aR6b, thus providing other
compounds of
Formula 4b.
Compounds of Formulae 7 and 8 are available from commercial sources and can
easily be
prepared using commercial precursors and known methods. Present Example 1,
Step A, Example
6, Step D and Example 8, Step D illustrate the preparation of a compound of
Formula 7.
Scheme 8
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
105
0 OH
E R6a
0 J R
R6b
8 4b
R6a R6b
7
Scheme 9 illustrates a specific example of the general method of Scheme 8 for
the
preparation of a compound of Formula 4b1 (i.e. Formula 4b wherein L is CH2, J
is phenyl (i.e.
J-1), R6a and R6b are H and R1 is CF3) In this method a compound of Formula 7a
(i.e. Formula
7 wherein L is CH2 and J is phenyl (i.e. J-1)) is reacted with 2-
(trifluoromethyl)oxirane (i.e.
Formula 8a) in the presence of cesium carbonate in a solvent such as
acetonitrile at a temperature
between about 60 to 80 C. Present Example 1, Step B illustrates the method of
Scheme 9.
Scheme 9
1:1H OH
+ 0, cesium carbonate
N.--......CCF3 --CF3 E
7a 8a 4131
As illustrated in Scheme 10, ketones of Formula la (i.e. Formula 1 wherein T
is T-1 and
W is 0) may exist in equilibrium with their corresponding ketone hydrates
(i.e. dihydroxy) of
Formula lb (i.e. Formula 1 wherein T is T-2) wherein R2aX and R2bY are OH. The
predominance
of Formula la or Formula lb is dependent upon several factors, such as
environment and
structure. For example, in an aqueous environment ketones of Formula la can
react with water
to give ketone hydrates (also known as 1,1-geminal diols) of Formula lb.
Conversion back to the
keto-form can usually be achieved by treatment with a dehydrating agent such
as magnesium
sulfate or molecular sieves. When the ketone moiety is in close proximity to
an electron-
withdrawing group, such as when R1 is a trifluoromethyl group, the equilibrium
typically favors
the dihydrate form. In these cases, conversion back to the keto-form may
require a strong
dehydrating agent, such as phosphorus pentoxide (P205). For reaction
conditions see, for
example, Eur. J. Org. Chem. 2013, 3658-3661; and Chemical Communications 2013,
49(95),
11133-11148, and references cited therein.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
106
Scheme 10
0 R2a
/R2b
X Y
H20
A /j\ XR1
A
la dehydrating agent
lb
wherein R2aX and R2bY are both OH
As shown in Scheme 11, ketones of Formula la may also exist in equilibrium
with their
hemiketals, hemithioketals and hemiaminals of Formula 1b2 (i.e. Formula lb
wherein R2bY is
OH and R2a is other than H) along with their ketals, thioketals aminals of
Formula lb wherein
R2a and R2b are other than H. Compounds of Formula 1b2 can be prepared by
reacting a
compound of Formula la with a compound of formula R2aX-H (e.g., alcohols for X
being 0,
thiols for X being S or amines for X being NR5a), usually in the presence of
an catalysis, such as
a Bronsted (i.e. protic) acid or Lewis acid (e.g. BF3), (see, for example,
Master Organic Chemistry
(Online), On Acetals and Hemiacetals, May 28, 2010, www.masterorganic-
chemistry.com/2010/05/28/on-acetals-and-hemiacetals). In a subsequent step,
compounds of
Formula 1b2 can be treated with a compound of formula R2bY-H (e.g., alcohols
for Y being 0,
thiols for Y being S or amines for Y being NR5b) under dehydrating conditions,
or other means
of water removal that will drive the equilibrium in the reaction to the right,
to provide compounds
of Formula lb wherein R2a and R2b are other than H. Alternatively, ketones of
Formula la can
initially be treated with two equivalents (or an excess amount) of an alcohol,
thiol or amine
typically in the presence of a catalysis together with a dehydrating agent to
provide compounds
of Formula lb directly (see, for example, the preparation of the
dimethylketals using methanol
and trimethyl orthoformate in US 6,350,892).
Scheme 11
R2b
2a 2a
R, R,
X OH X Y
II RY-H
R2aX-H 2b
\ A R1 ______________________ A XR A 1 ¨ õ..===j,..,õ.. X 1
-
la 1132 lb
wherein R2a is other than H
wherein R2a and R2b are other than H
As illustrated in Scheme 12, cyclic ketals of Formula 1b3 (i.e. Formula lb
wherein X and
Y are 0, and R2a and R2b are taken together to form a 5- to 7-membered ring)
can be prepared by
treating the corresponding ketones of Formula la with haloalcohols (e.g., 2-
chloroethanol or 2-
bromopropanol) in the presence of a base such as potassium carbonate or
potassium tert-butoxide
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
107
and in as solvent such as acetonitrile or N,N-dimethylformamide (DMF). For
reactions conditions
see, Organic Letters 2006 8(17), 3745-3748.
Scheme 12
'2a 1211/
R
H0,11, Rh X Y
0
¨12-3 X
R I
ERI
base A
1 b3
wherein Rh is halogen
la wherein X and Y are O.
and
R2a and R2b are taken togher to fom a ring
The method of Scheme 12 is also useful for preparing cyclic ketals stating
from the
corresponding ketone hydrate form. Scheme 13 illustrates a specific example
where a ketone
hydrate of Formula 1134 (i.e. Formula lb wherein L is CH2, J is phenyl (i.e. J-
1), A is OCH2, R2aX
and R2bY are OH and R1 is CF3) is reacted with 2-chloroethanol in the presence
of potassium
carbonate in acetonitrile at a temperature between about 25 to 70 C to
provide a compound of
Formula 1b5 (i.e. Formula lb wherein L is CH2, J is phenyl (i.e. J-1), A is
OCH2, X and Y are 0,
R2a and R2b are taken together to form a 5-membered ring and R1 is CF3).
Present Example 2
illustrates the method of Scheme 13.
Scheme 13
0
HO OH OH
1:).)( CI C'')><CF:3
CF3 E
K2CO3
1b4 1b5
As shown in Scheme 14, Compounds of Formula 1b6 (i.e. compounds of Formula lb
wherein A is Ai_A2_cR6aR6b) wherein A1 is N(R7a), 0 or S and A2 is a direct
bond, or wherein
A1 is cR6cR6d and A2 is N(R7b), 0 or S can be prepared by reacting compounds
of Formula 9
wherein A1 is 0, S or N(R7a) and A2 is a direct bond, or where Al is cR6cR6d
and A2 is 0, S or
N(R7b) with compounds of Formula 10. The reaction is typically run in a
solvent such N,N-
dimethylformamide (DMF) or dimethyl sulfoxide with a base such as cesium or
potassium
carbonate or sodium hydride at a temperature between about 20 to 80 C. The
method of Scheme
14 is illustrated in Example 4, Step D.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
108
Scheme 14
R2a
R2a
R2b YR2b
X Y
A2
1' H A Ri
A R P29 I )(AC1 l'A2\i(K
9 R6a R6b R6a R6b
106
wherein Al is N(R7a), 0 or S and A2
wherein AI is N(R7a), 0 or S and A2 is a direct
is a direct bond, or wherein A1 is
bond, or wherein AI is CR6cR6d and A2 is N(R7b),
CR6cR6d and A2 is N(R7b), 0 or S
0 or S
Compounds of Formula 10 can be prepared using commercial precursors and known
methods. For example, as shown in Scheme 15, compounds of Formula 10a (i.e.
Formula 10
5 wherein R6a and R6b are H, X and Y are 0 and R2a and R2b are taken
together to form a 5-
membered ring) can be prepared reacting compounds of Formula 11 with
haloalcohols (e.g., 2-
chloroethanol or 3-bromopropanol) under basic conditions (e.g., potassium tert-
butoxide in a
solvent such as N,N-dimethylformamide or tetrahydrofuran) to provide compounds
of Formula
12. A variety of methods are disclosed in the chemical literature for the
conversion of ketones to
10 cyclic ketals and can be readily adapted to prepare compounds of Formula
12 (see, for example,
G. Hilgetag and A. Martini, Ed., Preparative Organic Chemistry, pp 381-387:
Wiley, New York,
1972, and references sited therein; also see present Example 4, Step A). The
ester moiety of the
resulting cyclic ketal of Formula 12 can be reduced to the corresponding
alcohol of Formula 13
by standard methods known to one skilled in the art (Example 4, Step B
illustrates a typical
procedure). The hydroxy moiety in the compounds of Formula 13 can then be
converted to a wide
variety of R29 groups to provide compounds of Formula 10a. For example, a
mesylate or tosylate
group can be installed by treating the alcohol with methanesulfonyl chloride
(mesyl chloride) or
4-toluenesulfonyl chloride (tosyl chloride) in the presence of a base such as
triethylamine at a
temperature between about 0 to 40 C and in a solvent such as dichloromethane.
A triflate group
can be installed by treating the alcohol with triflic anhydride (CF3502)20 as
illustrated in
Example 4, Step C. Compounds of Formula 11 are known and can be prepared by
methods known
to one skilled in the art.
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
109
Scheme 15
0 R
OH
,0yL 0 0
H3, Ri wherein Rh is halogen 0 0
>r C3
0 0
0
11 12 13
0 0
><R29
10a
Compounds of Formula lc (i.e. Formula 1 wherein T is T-3 and X is 0) can be
prepared
by reacting a compound of Formula la (i.e. Formula 1 wherein T is T-1 and W is
0) wherein at
least one of R6a and R6b is H with a compound of Formula 14 in the presence of
a base, as
illustrated in Scheme 16. Suitable bases include cesium or potassium carbonate
in a solvent such
as N,N-dimethylformamide (DMF) or dimethyl sulfoxide at temperatures from
about 20 to 80 C.
In some cases, the method of Scheme 16 results in a mixture of 0-alkylated
product (typically as
a mixture of (E)- and (Z)-isomers), along with C-alkylated product.
Purification can be achieved
using standard techniques such as column chromatography (see Magnetic
Resonance in Chemistry
1991, 29, 675-678). Compounds of Formula 14 are commercially available and can
be easily
synthesized by general methods known to one skilled in the art.
Scheme 16
0 oR2c
/
aõR2c .LR1
A base
EJR1
la 14 R2d
iC
wherein at least one La is a leaving group such as
of R6a and R6b is H Cl, Br, I, OMs, OTs or OTf
The method of Scheme 16 is also useful for preparing compounds of Formula lc
stating
from the corresponding ketone hydrate. Scheme 17 illustrates a specific
example where a ketone
hydrate of Formula 11)4 (i.e. Formula lb wherein L is CH2, J is phenyl (i.e. J-
1), A is OCH2, R2aX
and R2bY are OH and R1 is CF3) is reacted with iodoethane in the presence of
cesium carbonate
in dimethyl sulfoxide at a temperature between about 25 to 75 C to provide a
compound of
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
110
Formula 1c1 (i.e. Formula lc wherein L is CH2, J is phenyl (i.e. J-1), A is 0,
R2d is H, XR2c is
OCH2CH3 and R1 is CF3). Present Example 5 illustrates the method of Scheme 17.
Scheme 17
OCH2CH3
HO OH
0 0
)( CH3CH2I CF,
CF3
cesium carbonate
1c1
Compounds of Formula 1 wherein T is T-1 and W is S can be prepared from the
corresponding compounds wherein W is 0 by treatment with phosphorus
pentasulfide or 2,4-
bis(4-methoxypheny1)-1,3 -dithia-2,4-dipho sphetane-2,4-disulfide (Lawe s s
on' s reagent) in
solvents such as toluene, xylene or tetrahydrofuran. One skilled in the art
will also recognize that
the compounds of Formula 1 wherein T is T-1 and W is NR3 can be prepared from
the compounds
of Formula 1 wherein T is T-1 and W is 0 or S by treatment with an amine of
Formula R3NH2
under dehydrating conditions.
The E-L- moieties present in the compounds of Formula 1 and the intermediate
compounds
of Formulae 2 through 7 and 9 are common organic functional groups whose
methods of
preparation have been documented in the literature. One skilled in the art
will recognize that these
well-known chemistry classes (esters, amides, sulfonamides, sulfones, ethers,
carbamates, ureas,
heterocycles) can be readily prepared by a variety of methods (see, for
example,
WO 2018/080859, WO 2018/118781, WO 2018/187553 and WO 2019/010192).
It is recognized that some reagents and reaction conditions described above
for preparing
compounds of Formula 1 may not be compatible with certain functionalities
present in the
intermediates. In these instances, the incorporation of
protection/deprotection sequences or
functional group interconversions into the synthesis will aid in obtaining the
desired products.
The use and choice of the protecting groups will be apparent to one skilled in
chemical synthesis
(see, for example, T. W. Greene and P. G. M. Wuts, Protective Groups in
Organic Synthesis, 2nd
ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in
some cases, after the
introduction of a given reagent as it is depicted in any individual scheme, it
may be necessary to
perform additional routine synthetic steps not described in detail to complete
the synthesis of
compounds of Formula 1. One skilled in the art will also recognize that it may
be necessary to
perform a combination of the steps illustrated in the above schemes in an
order other than that
implied by the particular sequence presented to prepare the compounds of
Formula 1.
One skilled in the art will also recognize that compounds of Formula 1 and the
intermediates
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
111
described herein can be subjected to various electrophilic, nucleophilic,
radical, organometallic,
oxidation, and reduction reactions to add substituents or modify existing
substituents.
Without further elaboration, it is believed that one skilled in the art using
the preceding
description can utilize the present invention to its fullest extent. The
following Examples are,
therefore, to be construed as merely illustrative, and not limiting of the
disclosure in any way
whatsoever. Steps in the following Examples illustrate a procedure for each
step in an overall
synthetic transformation, and the starting material for each step may not have
necessarily been
prepared by a particular preparative run whose procedure is described in other
Examples or Steps.
Percentages are by weight except for chromatographic solvent mixtures or where
otherwise
indicated. Parts and percentages for chromatographic solvent mixtures are by
volume unless
otherwise indicated. 1H NMR spectra are reported in ppm downfield from
tetramethylsilane; "s"
means singlet, "br s" means broad singlet, "d" means doublet, "dd" means
doublet of doublets,
means triplet, "q" means quartet and "m" means multiplet. 19F NMR spectra are
reported in
ppm using trichlorofluoromethane as the reference.
EXAMPLE 1
Preparation of ethyl 1- ][4-(3,3,3-trifluoro-2,2-
dihydroxypropoxy)phenyl]methyl]-1H-pyrazole-
4-carboxylate (Compound 1)
Step A: Preparation of ethyl 1- [(4-hydroxyphenyl)methy1]-1H-pyrazole-
4-carboxylate
A mixture of ethyl 1H-pyrazole-4-carboxylate (1.40 g, 10 mmol), 4-
(chloromethyl)phenyl
acetate (2.0 g, 11 mmol) and potassium carbonate (1.6 g, 11 mmol) in N,N-
dimethylformamide
(10 mL) was stirred at room temperature for 16 h. Ethanol (10 mL) was added
and the reaction
mixture was heated at 65 C for 16 h, cooled, and poured into ice water. The
resulting precipitate
was collected by filtration, washed with water and air dried. The resulting
solid (2.0 g) was
crystalized from acetonitrile to provide the title compound as a white solid
melting at 113-115 C.
1H NMR (CDC13): 8 1.32 (t, 3H), 3.10 (d, 1H), 4.10-4.40 (m, 5H), 5.24 (s, 2H),
6.91 (d, 2H), 7.22
(d, 2H), 7.83 (s, 1H), 7.93 (s, 1H).
Step B: Preparation of ethyl 1- P-(3,3,3-trifluoro-2-
hydroxypropoxy)phenyl]methy1]-1H-
pyrazole-4-carboxylate
A mixture of ethyl 1- [(4-hydroxyphenyl)methy1]-1H-pyrazole-4-c arboxylate
(i.e. the
product of Step A) (2.36 g, 9.6 mmol), 2-(trifluoromethyl)oxirane (1.3 g, 11.6
mmol) and cesium
carbonate (50 mg, 0.15 mmol) in acetonitrile (20 mL) was heated at 65 C.
After 3 days, the
reaction mixture was cooled and concentrated under reduced pressure. The
resulting material was
purified by silica gel chromatography (eluting with a gradient of 0 to 50%
ethyl acetate in hexanes)
to provide the title compound as a white solid (2.46 g).
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
112
1H NMR (CDC13): 8 1.33 (t, 3H), 4.29 (q, 2H), 5.21 (s, 2H), 5.95 (br s, 1H),
6.76 (d, 2H), 7.09
(d, 2H), 7.84 (s, 1H), 7.95 (s, 1H).
19F NMR (CDC13): 8 ¨77.54.
Step C: Preparation of ethyl 1- P-(3 ,3 ,3 -trifluoro -2,2-dihy
droxypropoxy)phenyl] methyl] -
1H-pyrazole-4-carboxylate
A mixture of ethyl 1-P-(3,3,3-trifluoro-2-hydroxypropoxy)phenyl]methyl]-1H-
pyrazole-
4-carboxylate (i.e. the product of Step B) (1.23 g, 3.4 mmol) and Dess-Martin
periodinane (2.2 g,
5.2 mmol) in dichloromethane (20 mL) was stirred at room temperature for 16 h,
and then
concentrated under reduced pressure. The resulting material was dissolved in
ethyl acetate and
washed with sodium bisulfite solution (2 M aqueous solution), followed by
saturated aqueous
sodium bicarbonate solution. The organic layer was dried, filtered and the
filtrate was
concentrated under reduced pressure. The resulting tan solid (1.77 g) was
crystalized from
acetonitrile to provide the title compound, a compound of the present
invention, as solid needles
melting at 120-123 C.
1H NMR (CDC13): 8 1.32 (t, 3H), 3.80 (br s, 1.7H), 4.18 (s, 2H), 4.28 (q, 2H),
5.25 (s, 2H), 6.95
(d, 2H), 7.22 (d, 2H), 7.82 (s, 1H), 7.95 (s, 1H).
19F NMR (CDC13): 8 ¨84.92.
EXAMPLE 2
Preparation of ethyl 1-P-N-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxylphenyl]methyl]-1H-
pyrazole-4-carboxylate (Compound 32)
A mixture of ethyl 1-[[4-(3,3,3-trifluoro-2,2-dihydroxypropoxy)phenyl]methyl]-
1H-
pyrazole-4-carboxylate (i.e. the product of Example 1) (1.07 g, 3.0 mmol), 2-
chloroethanol
(0.24 g, 3.0 mmol) and potassium carbonate (0.5 g, 3.6 mmol) in N,N-
dimethylformamide
(3.5 mL) was stirred at room temperature for 16 h, and then heated at 65 C
(briefly). After
cooling to room temperature, the reaction mixture was concentrated under
reduced pressure. The
resulting material was diluted with diethyl ether and washed with saturated
aqueous sodium
chloride solution. The organic layer was dried, filtered and the filtrate was
concentrated under
reduced pressure to provide the title compound, a compound of the present
invention, as a
colorless oil (1.06 g).
1H NMR (CDC13): 8 1.32 (t, 3H), 4.21 (s, 4H), 4.23 (s, 2H), 4.27 (q, 2H), 5.24
(s, 2H), 6.94 (d,
2H), 7.20 (d, 2H), 7.81 (s, 1H), 7.93 (s, 1H).
19F NMR (CDC13): 8 ¨81.39.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
113
EXAMPLE 3
Preparation of ethyl 1-[[4-[[4,4-dimethy1-2-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxy]-
phenyllmethyl]-1H-pyrazole-4-carboxylate (Compound 12)
The title compound was prepared by a procedure analogous to Example 2.
.. 1H NMR (CDC13): 6 1.32 (t, 3H), 1.13 (s, 3H), 1.45 (s, 3H), 3.95 (d, 1H),
4.00 (d, 1H), 4.18 (m,
2H), 4.27 (q, 2H), 5.24 (s, 2H), 6.94 (d, 2H), 7.20 (d, 2H), 7.81 (s, 1H),
7.93 (s, 1H).
19F NMR (CDC13): 8 ¨81.01.
EXAMPLE 4
Alternative preparation of ethyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-
yl]methoxylpheny11-
methy1]-1H-pyrazole-4-carboxylate (Compound 32)
Step A: Preparation of methyl 2-(trifluoromethyl)-1,3-dioxolane-2-
carboxylate
To a mixture of methyl 3,3,3-trifluoro-2-oxopropanoate (31.2 g, 200 mmol) in
petroleum
ether (100 mL) was added 2-bromoethanol (25.0 g, 200 mmol) over a period of 15
minutes. The
reaction mixture was stirred at room temperature for 30 minutes, then cooled
to 5 C and
potassium carbonate (28 g, 200 mmol) was added with vigorous stirring.
Stirring was continued
for an additional 4 h at 5 C, and then the reaction mixture was allowed to
warm to room
temperature, diluted with diethyl ether (100 mL) and filtered. The filtrate
was concentrated under
reduced pressure, and the resulting material was dissolved in diethyl ether
(200 mL) and washed
with saturated aqueous sodium chloride solution (3x). The organic layer was
dried over
magnesium sulfate, filtered and the filtrate was concentrated under reduced
pressure to provide
the title compound as a colorless oil (29 g).
1H NMR (CDC13): 6 3.80 (s, 3H), 4.30 (m, 4H).
19F NMR (CDC13): 6 ¨80.52.
Step B: Preparation of 2-(trifluoromethyl)-1,3-dioxolane-2-methanol
To a mixture of methyl 2-(trifluoromethyl)-1,3-dioxolane-2-carboxylate (i.e.
the product
of Step A) (5 g, 25 mmol) in tetrahydrofuran (75 mL) was added sodium bis(2-
methoxy-
ethoxy)aluminum hydride (60% in toluene) (12.2 mL, 37.5 mmol). The reaction
mixture was
heated at 40 C for 1.5 h, and then cooled to room temperature and a solution
of ethyl acetate
(3.30 g, 37.5 mmol) in tetrahydrofuran (15 mL) was added dropwise over a
period of 15 minutes.
The reaction mixture was stirred for 45 minutes and then concentrated under
reduced pressure.
The resulting material was diluted with diethyl ether (400 mL), washed with
saturated aqueous
sodium chloride solution (2x), dried over magnesium sulfate and filtered. The
filtrate was
concentrated under reduced pressure to provide the title compound as an oil
(3.8 g).
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
114
1H NMR (CDC13): 6 2.59 (t, 1H), 3.82 (d, 2H), 4.19 (m, 4H).
19F NMR (CDC13): 6 ¨81.50.
Step C: Preparation of [2- (trifluoromethyl)-1,3 -dio xolan-2-yl]
methyl 1,1,1-trifluoro-
methanesulfonate
A mixture of 2-(trifluoromethyl)-1,3-dioxolane-2-methanol (i.e. the product of
Step B)
(1.67 g, 9.70 mmol) and triethylamine (1.5 mL, 10.8 mmol) in dichloromethane
(50 mL) was
cooled to ¨78 C, and then a solution of trifluoromethanesulfonic anhydride
(1.81 mL,
10.8 mmol) in dichloromethane (50 mL) was added over a period of 30 minutes.
The reaction
mixture was stirred at ¨78 C for 1.5 h, and then water (50 mL) was added
dropwise while
allowing the reaction to warm to room temperature. The resulting mixture was
partitioned
between dichloromethane-water, and the organic layer washed with water, dried
over magnesium
sulfate and filtered. The filtrated was concentrated under reduced pressure to
provide the title
compound as a colorless solid (3.0 g).
1H NMR (CDC13): 6 4.24 (m, 4H), 4.60 (br s, 2H).
19F NMR (CDC13): 6 ¨74.84, ¨81.50.
Step D: Preparation of ethyl 1- [[4- [[2-(trifluoromethyl)-1,3-dioxolan-
2-yl[methoxyl -
phenyl[methyll-1H-pyrazole-4-carboxylate
To a mixture of ethyl 1-[(4-hydroxyphenyl)methyl]-1H-pyrazole-4-carboxylate
(i.e. the
product of Example 1, Step A) (16.85 g, 68.0 mmol) and cesium carbonate (53.53
g, 164.5 mmol)
in N,N-dimethylformamide (100 mL) was added [2-(trifluoromethyl)-1,3-dioxolan-
2-yl[methyl
1,1,1-trifluoromethanesulfonate (i.e. the product of Step C) (24.9 g, 82.0
mmol). The reaction
mixture was stirred for 24 h at room temperature, and then diluted with
diethyl ether. The organic
layer was washed with saturated aqueous sodium chloride solution, dried over
magnesium sulfate,
filtered and the filtrate was concentrated under reduced pressure. The
resulting material was
purified by silica gel chromatography (eluting with a gradient of 0 to 60%
ethyl acetate in hexanes)
to provide the title compound, a compound of the present invention, as a white
solid (23 g) melting
at 59-60 C.
1H NMR (CDC13): 6 1.32 (t, 3H), 4.21 (s, 4H), 4.23 (s, 2H), 4.27 (q, 2H), 5.24
(s, 2H), 6.94 (d,
2H), 7.20 (d, 2H), 7.81 (s, 1H), 7.93 (s, 1H).
19F NMR (CDC13): 6 ¨81.39.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
115
EXAMPLE 5
Preparation of ethyl 1- [[4- [[(1Z)-2-ethoxy-3,3,3-trifluoro-1-propen-1-
yl]oxylphenyllmethyl] -
1H-pyrazole-4-carboxylate (Compound 64)
A mixture of ethyl 1-[[4-(3,3,3-trifluoro-2,2-dihydroxypropoxy)phenyl]methyl]-
1H-
pyrazole-4-carboxylate (i.e. the product of Example 1) (1.0 g, 2.67 mmol),
iodoethane (2.5 g,
16 mmol) and cesium carbonate (1.75 g, 5.37 mmol) in dimethyl sulfoxide (10
mL) was heated at
40 C for 45 minutes. The reaction mixture was diluted with diethyl ether,
washed with water and
saturated aqueous sodium chloride solution, dried and filtered. The filtrate
was concentrated
under reduced pressure to provide the title compound, a compound of the
present invention, as a
white solid (0.80 g). A portion of the solid was further purified by silica
gel chromatography
(eluting with a gradient of 0 to 50% ethyl acetate in hexanes) to provide a
solid melting at 59-
60 C. A nuclear Overhauser effect (NOE) was observed between the
trifluoromethyl moiety and
the vinyl proton indicating a cis-configuration.
1H NMR (CDC13): 6 1.30-1.40 (m, 6H), 4.17 (q, 2H), 4.27 (q, 2H), 5.28 (s, 2H),
6.78 (q, 1H),
7.05 (m, 2H), 7.29 (m, 2H), 7.86 (s, 1H), 7.94 (s, 1H).
19F NMR (CDC13): 6 ¨70.13.
EXAMPLE 6
Preparation of ethyl 1-[[3-(3,3,3-trifluoro-2,2-
dihydroxypropoxy)phenyl]methyl]-1H-pyrazole-
4-carboxylate (Compound 266)
Step A: Preparation of 3-(bromomethyl)phenol
A mixture of 1-(bromomethyl)-3-methoxybenzene (15.48 g, 76.99 mmol) in
dichloromethane (150 mL) was cooled to -78 C, and then boron tribromide (1 M
solution in
dichloromethane) was added dropwise. The reaction mixture was allowed to warm
to room
temperature, stirred for 2 h, and then cooled to ¨20 C and methanol (150 mL)
was added
dropwise. After warming to room temperature, the reaction mixture was
concentrated under
reduced pressure and the resulting material was diluted with dichloromethane
and washed with
saturated aqueous sodium bicarbonate solution. The organic layer was dried
over magnesium
sulfate, filtered and the filtrate was concentrated under reduced pressure.
The resulting material
was purified by silica gel chromatography (eluting with a gradient of 0 to
100% ethyl acetate in
hexanes) to provide the title compound as a white solid (14.16 g).
1H NMR (CDC13): 6 4.44 (s, 2H), 4.89 (s, 1H), 6.76 (dd, 1H), 6.87 (s, 1H),
6.95 (d, 1H), 7.19-
7.23 (t, 1H).
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
116
Step B: Preparation of 3-(bromomethyl)phenyl acetate
A solution of 3-(bromomethyl)phenol (i.e. the product of Step A) (14.16 g,
75.7 mmol) in
dichloromethane (130 mL) was cooled to 0 C, and then acetic anhydride was
added (12.96 g,
12 mL, 126.9 mmol), followed by concentrated sulfuric acid (5 drops). The
reaction mixture was
allowed to warm to room temperature, stirred for 1 h, and then saturated
aqueous sodium
bicarbonate solution (300 mL, 318 mmol) was added. The organic layer was
separated, washed
with water, dried over magnesium sulfate, filtered and the filtrate was
concentrated under reduced
pressure to provide the title compound as a solid (16.68 g).
1H NMR (CDC13): 8 4.47 (s, 2H), 7.02-7.04 (m, 1H), 7.14 (s, 1H), 7.25 (m, 1H),
7.35 (t, 1H).
Step C: Preparation of ethyl 1-V-(acetyloxy)phenyl]methyl]-1H-pyrazole-4-
carboxylate
To a mixture of 3-(bromomethyl)phenyl acetate (i.e. the product of Step B)
(16.68 g,
72.8 mmol) in acetonitrile (300 mL) was added ethyl 1H-pyrazole-4-carboxylate
(10.61 g,
75.7 mmol) followed by potassium carbonate (19.35 g, 140 mmol). The reaction
mixture was
heated at 70 C overnight, cooled to room temperature and filtered. The
filtrate was concentrated
under reduced pressure to provide the title compound as a yellow oil (20.5 g).
1H NMR (CDC13): 8 2.30 (s, 3H), 4.47 (s, 2H), 7.02 (dd, 1H), 7.15 (s, 1H),
7.25 (m, 1H).
Step D: Preparation of ethyl 1-[(3-hydroxyphenyl)methyl]-1H-pyrazole-4-
carboxylate
To a mixture of ethyl 1-0-(acetyloxy)phenyl]methyl]-1H-pyrazole-4-carboxylate
(i.e. the
product of Step C) (20.5 g, 72.8 mmol) in ethanol was added potassium
carbonate (10.1 g,
73 mmol). The reaction mixture was heated at reflux for 3 h, cooled to room
temperature and
filtered. The filtrate was concentrated under reduced pressure and the
resulting material was
purified by MPLC silica gel chromatography (eluting with a gradient of 0 to
100% ethyl acetate
in hexanes) to provide the title compound as a white solid (10.02 g).
1H NMR (CDC13): 8 1.33 (t, 3H) 4.29 (q, 2H), 5.20 (br s, 1H), 5.25 (s, 2H),
6.66 (m, 1H), 6.78-
6.81 (m, 2H), 7.21-7.24 (m, 1H), 7.87 (s, 1H), 7.94 (s, 1H).
Step E: Preparation of ethyl 1-V-(3,3,3-trifluoro-2-
hydroxypropoxy)phenyl]methyl]-1H-
pyrazole-4-carboxylate
To a mixture of ethyl 1[(3-hydroxyphenyl)methy1]-1H-pyrazole-4-carboxylate
(i.e. the
product of Step D) (2.38 g 9.66 mmol) in acetonitrile (100 mL) was added 3-
bromo-1,1,1-
trifluoro-2-propanol (1.93 g, 1.04 mL, 10 mmol) followed by potassium
carbonate (2.86 g,
20.7 mmol). The reaction mixture was heated at reflux for 48 h, cooled to room
temperature,
filtered and the filtrate was concentrated under reduced pressure. The
resulting material was
purified by MPLC silica gel chromatography, (eluting with a gradient of 0 to
100% ethyl acetate
in hexanes) to provide the title compound as a solid (2.75 g).
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
117
1H NMR (CDC13): 6 1.33 (q, 3H), 4.1-4.4 (m, 5H), 5.27 (s, 2H), 6.80 (m, 1H),
6.87-6.89 (m, 2H),
7.28-7.31 (m, 1H), 7.88 (s, 1H), 7.94 (s, 1H).
19F NMR (CDC13): 6 ¨77.53.
Step F: Preparation of ethyl 1-V-(3,3,3-trifluoro-2,2-
dihydroxypropoxy)phenyl]methyl]-
1H-pyrazole-4-carboxylate
To a mixture of ethyl 1-V-(3,3,3-trifluoro-2-hydroxypropoxy)phenyl]methyl]-1H-
pyrazole-4-carboxylate (i.e. the product of Step E) (5.7 g, 14.9 mmol) in
dichloromethane
(300 mL) was added Dess-Martin periodinane (9.13 g, 20.3 mmol) in one portion.
After 3 h, the
reaction mixture was concentrated under reduced pressure, diluted with ethyl
acetate and washed
with sodium bisulfite solution (10% aqueous solution), saturated aqueous
sodium bicarbonate
solution and saturated aqueous sodium chloride solution. The organic layer was
dried over
magnesium sulfate, filtered and the filtrate was concentrated under reduced
pressure. The
resulting material was triturated with 1-chlorobutane to provide the title
compound, a compound
of the present invention, as a white solid (4.89 g).
1H NMR (DMSO-d6): 6 1.27 (t, 3H), 4.01 (s, 2H), 4.20 (m, 2H), 5.33 (s, 2H),
6.86-6.92 (m, 3H),
7.26-7.29 (m, 1H), 7.31 (s, 2H,), 7.87 (s, 1H), 8.48 (s, 1H).
19F NMR (DMSO-d6): 6 ¨81.82.
EXAMPLE 7
Preparation of ethyl 1- [[3- [[(1Z)-2-ethoxy-3 ,3 ,3 -trifluoro- 1-propen- 1-
yl] oxy] phenyl] methyl] -
1H-pyrazole-4-carboxylate (Compound 265)
To a mixture of ethyl 1-[[3-(3,3,3-trifluoro-2,2-
dihydroxypropoxy)phenyl]methyl]-1H-
pyrazole-4-carboxylate (i.e. the product of Example 6) (2.94 g, 7.85 mmol) in
dimethyl sulfoxide
(24 mL) was added iodoethane (2.39 g, 15.3 mmol). The reaction mixture was
heated at 65 C,
and then cesium carbonate (4.21 g, 12.92 mmol) was added. After 45 minutes,
the reaction
mixture was cooled to room temperature, and poured into diethyl ether/water
(400 mL, 1:1 ratio).
The organic layer was separated and washed with water, saturated aqueous
sodium chloride
solution, dried over magnesium sulfate, filtered and the filtrate was
concentrated under reduced
pressure. The resulting material was purified by silica gel chromatography
(eluting with a gradient
of 0 to 100% ethyl acetate in hexanes) to provide the title compound, a
compound of the present
invention, as a white solid (2.59 g) melting at 41-43 C.
1H NMR (CDC13): 6 1.32 (m, 6H), 4.16 (m, 2H,), 4.30 (m, 2H,), 5.31 (s, 2H,),
6.76 (s, 1H), 6.93
(m, 1H), 7.00-7.03 (m, 2H), 7.34-7.37 (m, 1H), 7.90 (s, 1H), 7.95 (s, 1H).
19F NMR (CDC13): 6 ¨70.09.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
118
EXAMPLE 8
Preparation of ethyl 1- [[4-(3 ,3 ,3 -trifluoro -2,2-dihydroxypropoxy)phenoxy
] methyl] - 1H-
pyrazole-4-carboxylate (Compound 366)
Step A: Preparation of ethyl 1-(hydroxymethyl)-1H-pyrazole-4-
carboxylate
A mixture of ethyl 1H-pyrazole-4-carboxylate (6.0 g, 43 mmol), formaldehyde
(37%
aqueous solution, 12 mL) and ethanol (50 mL) was heated at reflux overnight.
The reaction
mixture was cooled to room temperature and concentrated under reduced
pressure. The resulting
material was triturated with 1-chlorobutane to provide the title compound as a
white solid (6.2 g).
1H NMR (DMSO-d6): 8 1.27 (t, 3H) 4.22 (q, 2H), 5.41 (s, 2H), 7.89 (s, 1H),
8.36 (s, 1H).
Step B: Preparation of ethyl 1-(chloromethyl)-1H-pyrazole-4-carboxylate
To a mixture of ethyl 1-(hydroxymethyl)-1H-pyrazole-4-carboxylate (i.e. the
product of
Step A) (6.2 g, 36 mmol) in dichloroethane (100 mL) was added N,N-
dimethylformamide
(2 drops), followed by thionyl chloride (5.3 mL, 73 mmol) dropwise. After 3 h,
the reaction
mixture, was concentrated under reduced pressure to provide the title compound
as a yellow solid
(6.2g).
1H NMR (CDC13): 8 1.35 (t, 3H), 4.31 (q, 2H), 5.85 (s, 2H), 7.99 (s, 1H), 8.11
(s, 1H).
Step C: Preparation of ethyl 1- [(4-methoxyphenoxy)methy1]-1H-pyrazole-
4-carboxylate
A mixture of ethyl 1-(chloromethyl)-1H-pyrazole-4-carboxylate (i.e. the
product of Step B)
(2.0 g, 11 mmol), 4-methoxyphenol (1.24 g, 10 mmol), potassium carbonate (2.8
g, 20 mmol) and
N,N-dimethylformamide (25 mL) was stirred at room temperature. After 3 days,
the reaction
mixture was poured into ice water (150 mL) and extracted with diethyl ether (2
x 100 mL). The
combined organic layers were washed with water (50 mL), saturated aqueous
sodium chloride
solution (25 mL), dried over magnesium sulfate, filtered and the filtrate was
concentrated under
reduced pressure. The resulting material was purified by silica gel
chromatography (eluting with
a gradient of 10 to 100% ethyl acetate in hexanes) to provide the title
compound as a colorless oil
(2.7 g).
1H NMR (CDC13): 8 1.34 (t, 3H), 3.78 (s, 3H), 4.29 (q, 2H), 5.90 (s, 2H), 6.80-
6.84 (m, 2H), 6.88-
6.91 (m, 2H), 7.96 (s, 1H), 8.05 (s, 1H).
Step D: Preparation of ethyl 1- [(4-hydroxyphenoxy)methy1]-1H-pyrazole-
4-carboxylate
To a mixture of ethyl 1- [(4-methoxyphenoxy)methy1]-1H-pyrazole-4-carboxylate
(i.e. the
product of Step C) (1.7 g, 6.2 mmol) in dichloromethane (3 mL) was added boron
tribromide
solution (1 M in dichloromethane, 12.4 mL, 12.4 mmol). After 4 h, saturated
aqueous ammonium
chloride solution (25 mL) was added to the reaction mixture and stirring was
continued for another
15 minutes. The reaction mixture was diluted with dichloromethane (25 mL) and
saturated
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
119
aqueous ammonium chloride solution (25 mL). The organic layer was separated
and washed with
saturated aqueous sodium bicarbonate solution (25 mL) and saturated aqueous
sodium chloride
solution (25 mL), drying over magnesium sulfate and filtered. The filtrate was
concentrated under
reduced pressure to provide the title compound as a solid (1.65 g).
1H NMR (DMSO-d6): 8 1.26 (t, 3H), 4.21 (q, 2H), 5.76 (s, 1H), 5.96 (s, 2H),
6.62-6.71 (m, 2H),
6.82-6.88 (m, 2H), 7.93 (d, 1H), 8.48 (d, 1H).
Step E: Preparation of ethyl 1- [[4-(3,3,3-trifluoro-2-
hydroxypropoxy)phenoxy[methyll-
1H-pyrazole-4-carboxylate
To a mixture of ethyl 1-[(4-hydroxyphenoxy)methyl]-1H-pyrazole-4-carboxylate
(i.e. the
product of Step D) (6.2 mmol) in acetonitrile (20 mL) was added 2-
(trifluoromethyl)oxirane
(0.62 mL, 7.6 mmol) and cesium carbonate (approximately 10 mg). The reaction
mixture was
heated at 75 C overnight, and then cooled to room temperature and
concentrated under reduced
pressure. The resulting material was purified by silica gel chromatography
(eluting with a gradient
of 10 to 100% ethyl acetate in hexanes) to provide the title compound as a
white solid (0.95 g).
1H NMR (DMSO-d6): 8 1.26 (t, 3H), 3.96-4.08 (m, 1H), 4.12 (dd, 1H), 4.22 (q,
2H), 4.33-4.36
(m, 1H), 6.04 (s, 2H), 6.62 (d, 1H), 6.88-6.97 (m, 2H), 7.00-7.03 (m, 2H),
7.95 (s, 1H), 8.54 (s,
1H).
Step F: Preparation of ethyl 1- [[4-(3,3,3-trifluoro-2,2-
dihydroxypropoxy)phenoxy]-
methyl]-1H-pyrazole-4-carboxylate
To a mixture of ethyl 1- [[4-(3,3,3-trifluoro-2-hydroxypropoxy)phenoxy[methyl[-
1H-
pyrazole-4-carboxylate (i.e. the product of Step E) (0.95 g, 2.5 mmol) in
dichloromethane
(25 mL) was added Dess-Martin periodinane (1.5 g, 3.5 mmol) in one portion.
The reaction
mixture was stirred for 2.5 h, and then saturated aqueous sodium thiosulfate
solution (30 mL) was
added and the mixture was concentrated under reduced pressure. The resulting
mixture was
extracted with ethyl acetate (150 mL) and the combined organic layers were
washed with
saturated aqueous sodium thiosulfate solution (50 mL), saturated aqueous
sodium bicarbonate
solution (50 mL) and saturated aqueous sodium chloride solution (25 mL),
drying over
magnesium sulfate and filtered. The filtered was concentrated under reduced
pressure and the
resulting material was triturated with dichloromethane to provide the title
compound, a compound
of the present invention, as a solid (0.65 g).
1H NMR (DMSO-d6): 8 1.26 (t, 3H), 3.98 (s, 2H), 4.21 (q, 2H), 6.03 (s, 2H),
6.86-6.94 (m, 2H),
6.95-7.06 (m, 2H), 7.27 (s, 2H), 7.94 (s, 1H), 8.53 (s, 1H).
EXAMPLE 9
Preparation of ethyl 1- [[4- [[(1Z)-2 -ethoxy-3 ,3 ,3 -trifluoro- 1-propen- 1-
y1] oxyl phenoxyl methyl] -
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
120
1H-pyrazole-4-carboxylate (Compound 364)
A mixture of iodoethane (2.7 mL, 34 mmol), potassium carbonate (0.84 g, 6.1
mmol) and
dimethyl sulfoxide (7 mL) was stirred at room temperature for 20 minutes, and
then a solution of
ethyl 1- [[4-(3 ,3 ,3 -trifluoro-2,2-dihydroxypropoxy )phenoxy] methyl] - 1H-
pyrazole-4-c arboxylate
(i.e. the product of Example 8) (0.64 g, 1.6 mmol) in dimethyl sulfoxide (7
mL) was added
portionwise over 20 minutes. After stirring at room temperature for 1.5 hours,
the reaction
mixture was poured into ice water (150 mL) and extracted with ethyl acetate
(125 mL). The
organic layer was washed with water (2 x 50 mL) and saturated aqueous sodium
chloride solution
(50 mL), drying over magnesium sulfate and filtered. The filtrate was
concentrated under reduced
pressure and the resulting material was purified by silica gel chromatography
(eluting with a
gradient of 10 to 100% ethyl acetate in hexanes) to provide the title
compound, a compound of
the present invention, as a colorless oil (0.46 g).
1H NMR (DMSO-d6): 6 1.23-1.27 (m, 6H), 4.11 (q, 2H), 4.22 (q, 2H), 6.10 (s,
2H), 7.07-7.24
(m, 4H) 7.95 (s, 1H) 8.58 (s, 1H).
By the procedures described herein, together with methods known in the art,
the following
compounds of Tables 1, 1A-48A, 2, and 1B-48B can be prepared. The following
abbreviations
are used in the Tables: t means tertiary, s means secondary, n means normal, i
means iso, c means
cyclo, Me means methyl, Et means ethyl, Pr means propyl, i-Pr means isopropyl,
c-Pr means
cyclopropyl, Bu means butyl, i-Bu means isobutyl, t-Bu means tert-butyl, and
Ph means phenyl.
Table 1
(R13)x HO OH
G /()
CF3
In the above formula, E is equal to E2, E2 is equal G-Z-, and G is optionally
substituted with R13. The
definitions of G are as defined Exhibit A in the above Embodiments. In the
column G, the number in parentheses
refers to the attachment point of the G-ring to Z. The (R13)x column refers to
the substituent(s) attached to the
G-ring as shown in Exhibit A above. A dash "¨" in the (R13)x column means that
no R13 substituent is present
and the remaining valences on the G-ring are occupied by hydrogen atoms.
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
(R13)x G (R13)x
G-1(4) G-12(1)
G-1 (4) 2-Me G-12 (1) 4-Me
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
121
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-1 (4) 2-Et G-12 (1) 4-Et
G-1 (4) 2-n-Pr G-12 (1) 4-n-Pr
G-1 (4) 2-i-Pr G-12 (1) 4-i-Pr
G-1 (4) 2-c-Pr G-12 (1) 4-c-Pr
G-1 (4) 2-n-Bu G-12 (1) 4-n-Bu
G-1 (4) 2-i-Bu G-12 (1) 4-i-Bu
G-1 (4) 2-t-Bu G-12 (1) 4-t-Bu
G-1 (4) 2-F G-12 (1) 4-F
G-1 (4) 2-C1 G-12 (1) 4-C1
G-1 (4) 2-Br G-12 (1) 4-Br
G-1 (4) 2-CF3 G-12 (1) 4-CF3
G-1 (4) 2-HO G-12 (1) 4-HO
G-1 (4) 2-NEC G-12 (1) 4-NEC
G-1 (4) 2-I\TCCH2 G-12 (1) 4-I\TCCH2
G-1 (4) 2-(Me0) G-12 (1) 4-(Me0)
G-1 (4) 2-(MeOCH2) G-12 (1) 4-(MeOCH2)
G-1 (4) 2-(EtOCH2) G-12 (1) 4-(EtOCH2)
G-1 (4) 2-(CH(=0)) G-12 (1) 4-(CH(=0))
G-1 (4) 2-(HOC(=0)) G-12 (1) 4-(HOC(=0))
G-1 (4) 2-(Me0C(=0)) G-12 (1) 4-(Me0C(=0))
G-1 (4) 2-(Et0C(=0)) G-12 (1) 4-(Et0C(=0))
G-1 (4) 2-(i-PrOC(=0)) G-12 (1) 4-(i-PrOC(=0))
G-1 (4) 2-(n-PrOC(=0)) G-12 (1) 4-(n-PrOC(=0))
G-1 (4) 2-(BuOC(=0)) G-12 (1) 4-(BuOC(=0))
G-1 (4) 2-(i-BuOC(=0)) G-12 (1) 4-(i-BuOC(=0))
G-1 (4) 2-(t-BuOC(=0)) G-12 (1) 4-(t-BuOC(=0))
G-1 (4) 2-(CF3CH20C(=0) G-12 (1) 4-(CF3CH20C(=0)
G-1 (4) 2-(CH2=CHOC(=0)) G-12 (1) 4-(CH2=CHOC(=0))
G-1 (4) 2-(CH2=CHCH20C(=0)) G-12 (1) 4-(CH2=CHCH20C(=0))
G-1 (4) 2-(CH2=CBrCH20C(=0)) G-12 (1) 4-(CH2=CBrCH20C(=0))
G-1 (4) 2-(CH2=CHCF20C(=0)) G-12 (1) 4-(CH2=CHCF20C(=0))
G-1 (4) 2-(Me2C=CHCH20C(=0)) G-12 (1) 4-(Me2C=CHCH20C(=0))
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
122
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-1 (4) 2-(CH2=C(Me)CH20C(=0)) G-12 (1) 4-(CH2=C(Me)CH20C(=0))
G-1 (4) 2-(CHCCH20C(=0)) G-12 (1) 4-(CHCCH20C(=0))
G-1 (4) 2-(NCCH20C(=0)) G-12 (1) 4-(NCCH20C(=0))
G-1 (4) 2-(MeNHC(=0)) G-12 (1) 4-(MeNHC(=0))
G-1 (4) 2-(Me2NC(=0)) G-12 (1) 4-(Me2NC(=0))
G-1 (4) 2-(MeNHC(=0)) G-12 (1) 4-(MeNHC(=0))
G-1 (4) 2-(EtNHC(=0)) G-12 (1) 4-(EtNHC(=0))
G-1 (4) 2-(PrNHC(=0)) G-12 (1) 4-(PrNHC(=0))
G-1 (4) 2-(i-PrNHC(=0)) G-12 (1) 4-(i-PrNHC(=0))
G-1 (4) 2-(BuNHC(=0)) G-12 (1) 4-(BuNHC(=0))
G-1 (4) 2-(t-BuNHC(=0)) G-12 (1) 4-(t-BuNHC(=0))
G-1 (4) 2-(i-BuNHC(=0)) G-12 (1) 4-(i-BuNHC(=0))
G-1 (4) 2-(CF3CH2NHC(=0)) G-12 (1) 4-(CF3CH2NHC(=0))
G-1 (4) 2-(c-PrCH2NHC(=0)) G-12 (1) 4-(c-PrCH2NHC(=0))
G-1 (4) 2-(MeOCH2NHC(=0)) G-12 (1) 4-(MeOCH2NHC(=0))
G-1 (4) 2-(MeOCH2CH2NHC(=0)) G-12 (1) 4-(MeOCH2CH2NHC(=0))
G-1 (4) 2-(CH2=CHCH2NHC(=0)) G-12 (1) 4-(CH2=CHCH2NHC(=0))
G-1 (4) 2-(NCCH2NHC(=0)) G-12 (1) 4-(NCCH2NHC(=0))
G-1 (4) 2-(OH-N=CH) G-12 (1) 4-(OH-N=CH)
G-1 (4) 2-(Me2NN=CH) G-12 (1) 4-(Me2NN=CH)
G-1 (4) 2-(Me0C(=0)NHN=CH) G-12 (1) 4-(Me0C(=0)NHN=CH)
G-1 (4) 2-(OHC(=0)CH2ON=CH) G-12 (1) 4-(OHC(=0)CH2ON=CH)
G-1 (2) G-12 (1) 5-Me, 3-(Et0C(=0))
G-1 (2) 4-Me G-12 (1) 3-Me
G-1 (2) 4-Et G-12 (1) 3-Et
G-1 (2) 4-n-Pr G-12 (1) 3-n-Pr
G-1 (2) 4-i-Pr G-12 (1) 3-i-Pr
G-1 (2) 4-c-Pr G-12 (1) 3-c-Pr
G-1 (2) 4-n-Bu G-12 (1) 3-n-Bu
G-1 (2) 4-i-Bu G-12 (1) 3-i-Bu
G-1 (2) 4-t-Bu G-12 (1) 3-t-Bu
G-1 (2) 4-F G-12 (1) 3-F
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
123
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-1 (2) 4-C1 G-12 (1) 3-C1
G-1 (2) 4-Br G-12 (1) 3-Br
G-1 (2) 4-CF3 G-12 (1) 3-CF3
G-1 (2) 4-HO G-12 (1) 3-HO
G-1 (2) 4-NEC G-12 (1) 3-NEC
G-1 (2) 4-I\TCCH2 G-12 (1) 3-I\TCCH2
G-1 (2) 4-(Me0) G-12 (1) 3-(Me0)
G-1 (2) 4-(MeOCH2) G-12 (1) 3-(MeOCH2)
G-1 (2) 4-(EtOCH2) G-12 (1) 3-(EtOCH2)
G-1 (2) 4-(CH(=0)) G-12 (1) 3-(CH(=0))
G-1 (2) 4-(HOC(=0)) G-12 (1) 3-(HOC(=0))
G-1 (2) 4-(Me0C(=0)) G-12 (1) 3-(Me0C(=0))
G-1 (2) 4-(Et0C(=0)) G-12 (1) 3-(Et0C(=0))
G-1 (2) 4-(i-PrOC(=0)) G-12 (1) 3-(i-PrOC(=0))
G-1 (2) 4-(n-PrOC(=0)) G-12 (1) 3-(n-PrOC(=0))
G-1 (2) 4-(BuOC(=0)) G-12 (1) 3-(BuOC(=0))
G-1 (2) 4-(i-BuOC(=0)) G-12 (1) 3-(i-BuOC(=0))
G-1 (2) 4-(t-BuOC(=0)) G-12 (1) 3-(t-BuOC(=0))
G-1 (2) 4-(CF3CH20C(=0) G-12 (1) 3-(CF3CH20C(=0)
G-1 (2) 4-(CH2=CHOC(=0)) G-12 (1) 3-(CH2=CHOC(=0))
G-1 (2) 4-(CH2=CHCH20C(=0)) G-12 (1) 3-(CH2=CHCH20C(=0))
G-1 (2) 4-(CH2=CBrCH20C(=0)) G-12 (1) 3-(CH2=CBrCH20C(=0))
G-1 (2) 4-(CH2=CHCF20C(=0)) G-12 (1) 3-(CH2=CHCF20C(=0))
G-1 (2) 4-(Me2C=CHCH20C(=0)) G-12 (1) 3-(Me2C=CHCH20C(=0))
G-1 (2) 4-(CH2=C(Me)CH20C(=0)) G-12 (1) 3-(CH2=C(Me)CH20C(=0))
G-1 (2) 4-(CHCCH20C(=0)) G-12 (1) 3-(CHCCH20C(=0))
G-1 (2) 4-(NCCH20C(=0)) G-12 (1) 3-(NCCH20C(=0))
G-1 (2) 4-(MeNHC(=0)) G-12 (1) 3-(MeNHC(=0))
G-1 (2) 4-(Me2NC(=0)) G-12 (1) 3-(Me2NC(=0))
G-1 (2) 4-(MeNHC(=0)) G-12 (1) 3-(MeNHC(=0))
G-1 (2) 4-(EtNHC(=0)) G-12 (1) 3-(EtNHC(=0))
G-1 (2) 4-(PrNHC(=0)) G-12 (1) 3-(PrNHC(=0))
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
124
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-1 (2) 4-(i-PrNHC(=0)) G-12 (1) 3-(i-PrNHC(=0))
G-1 (2) 4-(BuNHC(=0)) G-12 (1) 3-(BuNHC(=0))
G-1 (2) 4-(t-BuNHC(=0)) G-12 (1) 3-(t-BuNHC(=0))
G-1 (2) 4-(i-BuNHC(=0)) G-12 (1) 3-(i-BuNHC(=0))
G-1 (2) 4-(CF3CH2NHC(=0)) G-12 (1) 3-(CF3CH2NHC(=0))
G-1 (2) 4-(c-PrCH2NHC(=0)) G-12 (1) 3-(c-PrCH2NHC(=0))
G-1 (2) 4-(MeOCH2NHC(=0)) G-12 (1) 3-(MeOCH2NHC(=0))
G-1 (2) 4-(MeOCH2CH2NHC(=0)) G-12 (1) 3-(MeOCH2CH2NHC(=0))
G-1 (2) 4-(CH2=CHCH2NHC(=0)) G-12 (1) 3-(CH2=CHCH2NHC(=0))
G-1 (2) 4-(NCCH2NHC(=0)) G-12 (1) 3-(NCCH2NHC(=0))
G-1 (2) 4-(OH-N=CH) G-12 (1) 3-(OH-N=CH)
G-1 (2) 4-(Me2NN=CH) G-12 (1) 3-(Me2NN=CH)
G-1 (2) 4-(Me0C(=0)NHN=CH) G-12 (1) 3-(Me0C(=0)NHN=CH)
G-1 (2) 4-(OHC(=0)CH2ON=CH) G-12 (1) 3-(OHC(=0)CH2ON=CH)
G-3 (1) G-13 (1)
G-3 (1) 4-Me G-13 (1) 5-Me
G-3 (1) 4-Et G-13 (1) 5-Et
G-3 (1) 4-n-Pr G-13 (1) 5-n-Pr
G-3 (1) 4-i-Pr G-13 (1) 5-i-Pr
G-3 (1) 4-c-Pr G-13 (1) 5-c-Pr
G-3 (1) 4-n-Bu G-13 (1) 5-n-Bu
G-3 (1) 4-i-Bu G-13 (1) 5-i-Bu
G-3 (1) 4-t-Bu G-13 (1) 5-t-Bu
G-3 (1) 4-F G-13 (1) 5-F
G-3 (1) 4-C1 G-13 (1) 5-C1
G-3 (1) 4-Br G-13 (1) 5-Br
G-3 (1) 4-CF3 G-13 (1) 5-CF3
G-3 (1) 4-HO G-13 (1) 5-HO
G-3 (1) 4-NEC G-13 (1) 5-NEC
G-3 (1) 4-I\TCCH2 G-13 (1) 5-I\TCCH2
G-3 (1) 4-(Me0) G-13 (1) 5-(Me0)
G-3 (1) 4-(MeOCH2) G-13 (1) 5-(MeOCH2)
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
125
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is
CH2 and Z is a direct bond.
G (R13)x G (R13)x
G-3 (1) 4-(EtOCH2) G-13 (1) 5-(EtOCH2)
G-3 (1) 4-(CH(=0)) G-13 (1) 5-(CH(=0))
G-3 (1) 4-(HOC(=0)) G-13 (1) 5-(HOC(=0))
G-3 (1) 4-(Me0C(=0)) G-13 (1) 5-(Me0C(=0))
G-3 (1) 4-(Et0C(=0)) G-13 (1) 5-(Et0C(=0))
G-3 (1) 4-(i-PrOC(=0)) G-13 (1) 5-(i-PrOC(=0))
G-3 (1) 4-(n-PrOC(=0)) G-13 (1) 5-(n-
PrOC(=0))
G-3 (1) 4-(BuOC(=0)) G-13 (1) 5-(BuOC(=0))
G-3 (1) 4-(i-BuOC(=0)) G-13 (1) 5-(i-
BuOC(=0))
G-3 (1) 4-(t-BuOC(=0)) G-13 (1) 5-(t-
BuOC(=0))
G-3 (1) 4-(CF3CH20C(=0) G-13 (1) 5-(CF3CH20C(=0)
G-3 (1) 4-(CH2=CHOC(=0)) G-13 (1) 5-(CH2=CHOC(=0))
G-3 (1) 4-(CH2=CHCH20C(=0)) G-13 (1) 5-(CH2=CHCH20C(=0))
G-3 (1) 4-(CH2=CBrCH20C(=0)) G-13 (1) 5-(CH2=CBrCH20C(=0))
G-3 (1) 4-(CH2=CHCF20C(=0)) G-13 (1) 5-(CH2=CHCF20C(=0))
G-3 (1) 4-(Me2C=CHCH20C(=0)) G-13 (1) 5-(Me2C=CHCH20C(=0))
G-3 (1) 4-(CH2=C(Me)CH20C(=0)) G-13 (1) 5-(CH2=C(Me)CH20C(=0))
G-3 (1) 4-(CHCCH20C(=0)) G-13 (1) 5-(CHCCH20C(=0))
G-3 (1) 4-(NCCH20C(=0)) G-13 (1) 5-(NCCH20C(=0))
G-3 (1) 4-(MeNHC(=0)) G-13 (1) 5-
(MeNHC(=0))
G-3 (1) 4-(Me2NC(=0)) G-13 (1) 5-
(Me2NC(=0))
G-3 (1) 4-(MeNHC(=0)) G-13 (1) 5-
(MeNHC(=0))
G-3 (1) 4-(EtNHC(=0)) G-13 (1) 5-
(EtNHC(=0))
G-3 (1) 4-(PrNHC(=0)) G-13 (1) 5-
(PrNHC(=0))
G-3 (1) 4-(i-PrNHC(=0)) G-13 (1) 5-(i-
PrNHC(=0))
G-3 (1) 4-(BuNHC(=0)) G-13 (1) 5-
(BuNHC(=0))
G-3 (1) 4-(t-BuNHC(=0)) G-13 (1) 5-(t-BuNHC(=0))
G-3 (1) 4-(i-BuNHC(=0)) G-13 (1) 5-(i-BuNHC(=0))
G-3 (1) 4-(CF3CH2NHC(=0)) G-13 (1) 5-(CF3CH2NHC(=0))
G-3 (1) 4-(c-PrCH2NHC(=0)) G-13 (1) 5-(c-PrCH2NHC(=0))
G-3 (1) 4-(MeOCH2NHC(=0)) G-13 (1) 5-(MeOCH2NHC(=0))
G-3 (1) 4-(MeOCH2CH2NHC(=0)) G-13 (1) 5-(MeOCH2CH2NHC(=0))
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
126
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-3 (1) 4-(CH2=CHCH2NHC(=0)) G-13 (1) 5-(CH2=CHCH2NHC(=0))
G-3 (1) 4-(1\TCCH2NHC(=0)) G-13 (1) 5-(1\TCCH2NHC(=0))
G-3 (1) 4-(OH-N=CH) G-13 (1) 5-(OH-N=CH)
G-3 (1) 4-(Me2NN=CH) G-13 (1) 5-(Me2NN=CH)
G-3 (1) 4-(Me0C(=0)NHN=CH) G-13 (1) 5-(Me0C(=0)NHN=CH)
G-3 (1) 4-(OHC(=0)CH2ON=CH) G-13 (1) 5-(OHC(=0)CH2ON=CH)
G-9(1) G-17(1)
G-9 (1) 3-Me G-17 (1) 4-Me
G-9(1) 3-Et G-17(1) 4-Et
G-9(1) 3-n-Pr G-17(1) 4-n-Pr
G-9 (1) 3-i-Pr G-17 (1) 4-i-Pr
G-9 (1) 3-c-Pr G-17 (1) 4-c-Pr
G-9 (1) 3-n-Bu G-17 (1) 4-n-Bu
G-9 (1) 3-i-Bu G-17 (1) 4-i-Bu
G-9 (1) 3-t-Bu G-17 (1) 4-t-Bu
G-9(1) 3-F G-17(1) 4-F
G-9 (1) 3-C1 G-17 (1) 4-C1
G-9(1) 3-Br G-17(1) 4-Br
G-9 (1) 3-CF3 G-17 (1) 4-CF3
G-9(1) 3-HO G-17(1) 4-HO
G-9 (1) 3-NEC G-17 (1) 4-NEC
G-9 (1) 3-I\TCCH2 G-17 (1) 4-I\TCCH2
G-9 (1) 3-(Me0) G-17 (1) 4-(Me0)
G-9 (1) 3-(MeOCH2) G-17 (1) 4-(MeOCH2)
G-9 (1) 3-(EtOCH2) G-17 (1) 4-(EtOCH2)
G-9 (1) 3-(CH(=0)) G-17 (1) 4-(CH(=0))
G-9 (1) 3-(HOC(=0)) G-17 (1) 4-(HOC(=0))
G-9 (1) 3-(Me0C(=0)) G-17 (1) 4-(Me0C(=0))
G-9 (1) 3-(Et0C(=0)) G-17 (1) 4-(Et0C(=0))
G-9 (1) 3-(i-PrOC(=0)) G-17 (1) 4-(i-PrOC(=0))
G-9 (1) 3-(n-PrOC(=0)) G-17 (1) 4-(n-PrOC(=0))
G-9 (1) 3-(BuOC(=0)) G-17 (1) 4-(BuOC(=0))
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
127
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-9 (1) 3-(i-BuOC(=0)) G-17 (1) 4-(i-BuOC(=0))
G-9 (1) 3-(t-BuOC(=0)) G-17 (1) 4-(t-BuOC(=0))
G-9 (1) 3-(CF3CH20C(=0) G-17 (1) 4-(CF3CH20C(=0)
G-9 (1) 3-(CH2=CHOC(=0)) G-17 (1) 4-(CH2=CHOC(=0))
G-9 (1) 3-(CH2=CHCH20C(=0)) G-17 (1) 4-(CH2=CHCH20C(=0))
G-9 (1) 3-(CH2=CBrCH20C(=0)) G-17 (1) 4-(CH2=CBrCH20C(=0))
G-9 (1) 3-(CH2=CHCF20C(=0)) G-17 (1) 4-(CH2=CHCF20C(=0))
G-9 (1) 3-(Me2C=CHCH20C(=0)) G-17 (1) 4-(Me2C=CHCH20C(=0))
G-9 (1) 3-(CH2=C(Me)CH20C(=0)) G-17 (1) 4-(CH2=C(Me)CH20C(=0))
G-9 (1) 3-(CHCCH20C(=0)) G-17 (1) 4-(CHCCH20C(=0))
G-9 (1) 3-(NCCH20C(=0)) G-17 (1) 4-(NCCH20C(=0))
G-9 (1) 3-(MeNHC(=0)) G-17 (1) 4-(MeNHC(=0))
G-9 (1) 3-(Me2NC(=0)) G-17 (1) 4-(Me2NC(=0))
G-9 (1) 3-(MeNHC(=0)) G-17 (1) 4-(MeNHC(=0))
G-9 (1) 3-(EtNHC(=0)) G-17 (1) 4-(EtNHC(=0))
G-9 (1) 3-(PrNHC(=0)) G-17 (1) 4-(PrNHC(=0))
G-9 (1) 3-(i-PrNHC(=0)) G-17 (1) 4-(i-PrNHC(=0))
G-9 (1) 3-(BuNHC(=0)) G-17 (1) 4-(BuNHC(=0))
G-9 (1) 3-(t-BuNHC(=0)) G-17 (1) 4-(t-BuNHC(=0))
G-9 (1) 3-(i-BuNHC(=0)) G-17 (1) 4-(i-BuNHC(=0))
G-9 (1) 3-(CF3CH2NHC(=0)) G-17 (1) 4-(CF3CH2NHC(=0))
G-9 (1) 3-(c-PrCH2NHC(=0)) G-17 (1) 4-(c-PrCH2NHC(=0))
G-9 (1) 3-(MeOCH2NHC(=0)) G-17 (1) 4-(MeOCH2NHC(=0))
G-9 (1) 3-(MeOCH2CH2NHC(=0)) G-17 (1) 4-(MeOCH2CH2NHC(=0))
G-9 (1) 3-(CH2=CHCH2NHC(=0)) G-17 (1) 4-(CH2=CHCH2NHC(=0))
G-9 (1) 3-(NCCH2NHC(=0)) G-17 (1) 4-(NCCH2NHC(=0))
G-9 (1) 3-(OH-N=CH) G-17 (1) 4-(OH-N=CH)
G-9 (1) 3-(Me2NN=CH) G-17 (1) 4-(Me2NN=CH)
G-9 (1) 3-(Me0C(=0)NHN=CH) G-17 (1) 4-(Me0C(=0)NHN=CH)
G-9 (1) 3-(OHC(=0)CH2ON=CH) G-17 (1) 4-(OHC(=0)CH2ON=CH)
The present disclosure also includes Tables lA through 48A, each of which is
constructed
the same as Table 1 above, except that the row heading in Table 1 (i.e. "J is
J-1, L is CH2 and Z
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
128
is a direct bond") is replaced with the respective row headings shown below.
Table Row Heading Table Row Heading
1A J is J-1, L is CH2CH2 and Z is a direct bond. 25A J is J-10, L is
CH2 and Z is a direct bond.
2A J is J-1, L is CH2(Me) and Z is a direct bond. 26A J is J-10, L is
CH2CH2 and Z is a direct bond.
3A J is J-1, L is (CH2)3 and Z is a direct bond. 27A J is J-10, L is
CH2(Me) and Z is a direct bond.
4A J is J-1, L is CH2 and Z is 0. 28A J is J-10, L is (CH2)3 and Z is
a direct bond.
5A J is J-2, L is CH2 and Z is a direct bond. 29A J is J-10, L is CH2
and Z is O.
6A J is J-2, L is CH2CH2 and Z is a direct bond. 30A J is J-14, L is
CH2 and Z is a direct bond.
7A J is J-2, L is CH2(Me) and Z is a direct bond. 31A J is J-14, L is
CH2CH2 and Z is a direct bond.
8A J is J-2, L is (CH2)3 and Z is a direct bond. 32A J is J-14, L is
CH2(Me) and Z is a direct bond.
9A J is J-2, L is CH2 and Z is 0. 33A J is J-14, L is (CH2)3 and Z is
a direct bond.
10A J is J-6, L is CH2 and Z is a direct bond. 34A J is J-14, L is CH2
and Z is O.
11A J is J-6, L is CH2CH2 and Z is a direct bond. 35A J is J-3, L is
CH2 and Z is a direct bond.
12A J is J-6, L is CH2(Me) and Z is a direct bond. 36A J is J-3, L is
CH2CH2 and Z is a direct bond.
13A J is J-6, L is (CH2)3 and Z is a direct bond. 37A J is J-3, L is
CH2(Me) and Z is a direct bond.
14A J is J-6, L is CH2 and Z is 0. 38A J is J-3, L is (CH2)3 and Z is
a direct bond.
15A J is J-7, L is CH2 and Z is a direct bond. 39A J is J-3, L is CH2
and Z is 0.
16A J is J-7, L is CH2CH2 and Z is a direct bond. 40A J is J-4, L is
CH2 and Z is a direct bond.
17A J is J-7, L is CH2(Me) and Z is a direct bond. 41A J is J-4, L is
CH2CH2 and Z is a direct bond.
18A J is J-7, L is (CH2)3 and Z is a direct bond. 42A J is J-4, L is
CH2(Me) and Z is a direct bond.
19A J is J-7, L is CH2 and Z is 0. 43A J is J-4, L is (CH2)3 and Z is
a direct bond.
20A J is J-8, L is CH2 and Z is a direct bond. 44A J is J-4, L is CH2
and Z is 0.
21A J is J-8, L is CH2CH2 and Z is a direct bond. 45A J is J-5, L is
CH2 and Z is a direct bond.
22A J is J-8, L is CH2(Me) and Z is a direct bond. 46A J is J-5, L is
CH2CH2 and Z is a direct bond.
23A J is J-8, L is (CH2)3 and Z is a direct bond. 47A J is J-5, L is
CH2(Me) and Z is a direct bond.
24A J is J-8, L is CH2 and Z is 0. 48A J is J-5, L is (CH2)3 and Z is
a direct bond.
Table 2
CH3
(R13)x 0)
OL G
CF3
In the above formula, E is equal to E2, E2 is equal G-Z-, and G is optionally
substituted with R13. The
definitions of G are as defined Exhibit A in the above Embodiments. In the
column G, the number in parentheses
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
129
refers to the attachment point of the G-ring to Z. The (R13)x column refers to
the substituent(s) attached to the
G-ring as shown in Exhibit A above. A dash "¨" in the (R13)x column means that
no R13 substituent is present
and the remaining valences on the G-ring are occupied by hydrogen atoms.
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-1(4) G-12(1)
G-1 (4) 2-Me G-12 (1) 4-Me
G-1 (4) 2-Et G-12 (1) 4-Et
G-1 (4) 2-n-Pr G-12 (1) 4-n-Pr
G-1 (4) 2-i-Pr G-12 (1) 4-i-Pr
G-1 (4) 2-c-Pr G-12 (1) 4-c-Pr
G-1 (4) 2-n-Bu G-12 (1) 4-n-Bu
G-1 (4) 2-i-Bu G-12 (1) 4-i-Bu
G-1 (4) 2-t-Bu G-12 (1) 4-t-Bu
G-1 (4) 2-F G-12 (1) 4-F
G-1 (4) 2-C1 G-12 (1) 4-C1
G-1 (4) 2-Br G-12 (1) 4-Br
G-1 (4) 2-CF3 G-12 (1) 4-CF3
G-1 (4) 2-HO G-12 (1) 4-HO
G-1 (4) 2-NEC G-12 (1) 4-NEC
G-1 (4) 2-I\TCCH2 G-12 (1) 4-I\TCCH2
G-1 (4) 2-(Me0) G-12 (1) 4-(Me0)
G-1 (4) 2-(MeOCH2) G-12 (1) 4-(MeOCH2)
G-1 (4) 2-(EtOCH2) G-12 (1) 4-(EtOCH2)
G-1 (4) 2-(CH(=0)) G-12 (1) 4-(CH(=0))
G-1 (4) 2-(HOC(=0)) G-12 (1) 4-(HOC(=0))
G-1 (4) 2-(Me0C(=0)) G-12 (1) 4-(Me0C(=0))
G-1 (4) 2-(Et0C(=0)) G-12 (1) 4-(Et0C(=0))
G-1 (4) 2-(i-PrOC(=0)) G-12 (1) 4-(i-PrOC(=0))
G-1 (4) 2-(n-PrOC(=0)) G-12 (1) 4-(n-PrOC(=0))
G-1 (4) 2-(BuOC(=0)) G-12 (1) 4-(BuOC(=0))
G-1 (4) 2-(i-BuOC(=0)) G-12 (1) 4-(i-BuOC(=0))
G-1 (4) 2-(t-BuOC(=0)) G-12 (1) 4-(t-BuOC(=0))
G-1 (4) 2-(CF3CH20C(=0) G-12 (1) 4-(CF3CH20C(=0)
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
130
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-1 (4) 2-(CH2=CHOC(=0)) G-12 (1) 4-(CH2=CHOC(=0))
G-1 (4) 2-(CH2=CHCH20C(=0)) G-12 (1) 4-(CH2=CHCH20C(=0))
G-1 (4) 2-(CH2=CBrCH20C(=0)) G-12 (1) 4-(CH2=CBrCH20C(=0))
G-1 (4) 2-(CH2=CHCF20C(=0)) G-12 (1) 4-(CH2=CHCF20C(=0))
G-1 (4) 2-(Me2C=CHCH20C(=0)) G-12 (1) 4-(Me2C=CHCH20C(=0))
G-1 (4) 2-(CH2=C(Me)CH20C(=0)) G-12 (1) 4-(CH2=C(Me)CH20C(=0))
G-1 (4) 2-(CHCCH20C(=0)) G-12 (1) 4-(CHCCH20C(=0))
G-1 (4) 2-(NCCH20C(=0)) G-12 (1) 4-(NCCH20C(=0))
G-1 (4) 2-(MeNHC(=0)) G-12 (1) 4-(MeNHC(=0))
G-1 (4) 2-(Me2NC(=0)) G-12 (1) 4-(Me2NC(=0))
G-1 (4) 2-(MeNHC(=0)) G-12 (1) 4-(MeNHC(=0))
G-1 (4) 2-(EtNHC(=0)) G-12 (1) 4-(EtNHC(=0))
G-1 (4) 2-(PrNHC(=0)) G-12 (1) 4-(PrNHC(=0))
G-1 (4) 2-(i-PrNHC(=0)) G-12 (1) 4-(i-PrNHC(=0))
G-1 (4) 2-(BuNHC(=0)) G-12 (1) 4-(BuNHC(=0))
G-1 (4) 2-(t-BuNHC(=0)) G-12 (1) 4-(t-BuNHC(=0))
G-1 (4) 2-(i-BuNHC(=0)) G-12 (1) 4-(i-BuNHC(=0))
G-1 (4) 2-(CF3CH2NHC(=0)) G-12 (1) 4-(CF3CH2NHC(=0))
G-1 (4) 2-(c-PrCH2NHC(=0)) G-12 (1) 4-(c-PrCH2NHC(=0))
G-1 (4) 2-(MeOCH2NHC(=0)) G-12 (1) 4-(MeOCH2NHC(=0))
G-1 (4) 2-(MeOCH2CH2NHC(=0)) G-12 (1) 4-(MeOCH2CH2NHC(=0))
G-1 (4) 2-(CH2=CHCH2NHC(=0)) G-12 (1) 4-(CH2=CHCH2NHC(=0))
G-1 (4) 2-(NCCH2NHC(=0)) G-12 (1) 4-(NCCH2NHC(=0))
G-1 (4) 2-(OH-N=CH) G-12 (1) 4-(OH-N=CH)
G-1 (4) 2-(Me2NN=CH) G-12 (1) 4-(Me2NN=CH)
G-1 (4) 2-(Me0C(=0)NHN=CH) G-12 (1) 4-(Me0C(=0)NHN=CH)
G-1 (4) 2-(OHC(=0)CH2ON=CH) G-12 (1) 4-(OHC(=0)CH2ON=CH)
G-1 (2) G-12 (1) 5-Me, 3-(Et0C(=0))
G-1 (2) 4-Me G-12 (1) 3-Me
G-1 (2) 4-Et G-12 (1) 3-Et
G-1 (2) 4-n-Pr G-12 (1) 3-n-Pr
G-1 (2) 4-i-Pr G-12 (1) 3-i-Pr
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
131
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-1 (2) 4-c-Pr G-12 (1) 3-c-Pr
G-1 (2) 4-n-Bu G-12 (1) 3-n-Bu
G-1 (2) 4-i-Bu G-12 (1) 3-i-Bu
G-1 (2) 4-t-Bu G-12 (1) 3-t-Bu
G-1 (2) 4-F G-12 (1) 3-F
G-1 (2) 4-C1 G-12 (1) 3-C1
G-1 (2) 4-Br G-12 (1) 3-Br
G-1 (2) 4-CF3 G-12 (1) 3-CF3
G-1 (2) 4-HO G-12 (1) 3-HO
G-1 (2) 4-NEC G-12 (1) 3-NEC
G-1 (2) 4-I\TCCH2 G-12 (1) 3-I\TCCH2
G-1 (2) 4-(Me0) G-12 (1) 3-(Me0)
G-1 (2) 4-(MeOCH2) G-12 (1) 3-(MeOCH2)
G-1 (2) 4-(EtOCH2) G-12 (1) 3-(EtOCH2)
G-1 (2) 4-(CH(=0)) G-12 (1) 3-(CH(=0))
G-1 (2) 4-(HOC(=0)) G-12 (1) 3-(HOC(=0))
G-1 (2) 4-(Me0C(=0)) G-12 (1) 3-(Me0C(=0))
G-1 (2) 4-(Et0C(=0)) G-12 (1) 3-(Et0C(=0))
G-1 (2) 4-(i-PrOC(=0)) G-12 (1) 3-(i-PrOC(=0))
G-1 (2) 4-(n-PrOC(=0)) G-12 (1) 3-(n-PrOC(=0))
G-1 (2) 4-(BuOC(=0)) G-12 (1) 3-(BuOC(=0))
G-1 (2) 4-(i-BuOC(=0)) G-12 (1) 3-(i-BuOC(=0))
G-1 (2) 4-(t-BuOC(=0)) G-12 (1) 3-(t-BuOC(=0))
G-1 (2) 4-(CF3CH20C(=0) G-12 (1) 3-(CF3CH20C(=0)
G-1 (2) 4-(CH2=CHOC(=0)) G-12 (1) 3-(CH2=CHOC(=0))
G-1 (2) 4-(CH2=CHCH20C(=0)) G-12 (1) 3-(CH2=CHCH20C(=0))
G-1 (2) 4-(CH2=CBrCH20C(=0)) G-12 (1) 3-(CH2=CBrCH20C(=0))
G-1 (2) 4-(CH2=CHCF20C(=0)) G-12 (1) 3-(CH2=CHCF20C(=0))
G-1 (2) 4-(Me2C=CHCH20C(=0)) G-12 (1) 3-(Me2C=CHCH20C(=0))
G-1 (2) 4-(CH2=C(Me)CH20C(=0)) G-12 (1) 3-(CH2=C(Me)CH20C(=0))
G-1 (2) 4-(CHCCH20C(=0)) G-12 (1) 3-(CHCCH20C(=0))
G-1 (2) 4-(1\TCCH20C(=0)) G-12 (1) 3-(1\TCCH20C(=0))
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
132
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-1 (2) 4-(MeNHC(=0)) G-12 (1) 3-(MeNHC(=0))
G-1 (2) 4-(Me2NC(=0)) G-12 (1) 3-(Me2NC(=0))
G-1 (2) 4-(MeNHC(=0)) G-12 (1) 3-(MeNHC(=0))
G-1 (2) 4-(EtNHC(=0)) G-12 (1) 3-(EtNHC(=0))
G-1 (2) 4-(PrNHC(=0)) G-12 (1) 3-(PrNHC(=0))
G-1 (2) 4-(i-PrNHC(=0)) G-12 (1) 3-(i-PrNHC(=0))
G-1 (2) 4-(BuNHC(=0)) G-12 (1) 3-(BuNHC(=0))
G-1 (2) 4-(t-BuNHC(=0)) G-12 (1) 3-(t-BuNHC(=0))
G-1 (2) 4-(i-BuNHC(=0)) G-12 (1) 3-(i-BuNHC(=0))
G-1 (2) 4-(CF3CH2NHC(=0)) G-12 (1) 3-(CF3CH2NHC(=0))
G-1 (2) 4-(c-PrCH2NHC(=0)) G-12 (1) 3-(c-PrCH2NHC(=0))
G-1 (2) 4-(MeOCH2NHC(=0)) G-12 (1) 3-(MeOCH2NHC(=0))
G-1 (2) 4-(MeOCH2CH2NHC(=0)) G-12 (1) 3-(MeOCH2CH2NHC(=0))
G-1 (2) 4-(CH2=CHCH2NHC(=0)) G-12 (1) 3-(CH2=CHCH2NHC(=0))
G-1 (2) 4-(NCCH2NHC(=0)) G-12 (1) 3-(NCCH2NHC(=0))
G-1 (2) 4-(OH-N=CH) G-12 (1) 3-(OH-N=CH)
G-1 (2) 4-(Me2NN=CH) G-12 (1) 3-(Me2NN=CH)
G-1 (2) 4-(Me0C(=0)NHN=CH) G-12 (1) 3-(Me0C(=0)NHN=CH)
G-1 (2) 4-(OHC(=0)CH2ON=CH) G-12 (1) 3-(OHC(=0)CH2ON=CH)
G-3 (1) G-13 (1)
G-3 (1) 4-Me G-13 (1) 5-Me
G-3 (1) 4-Et G-13 (1) 5-Et
G-3 (1) 4-n-Pr G-13 (1) 5-n-Pr
G-3 (1) 4-i-Pr G-13 (1) 5-i-Pr
G-3 (1) 4-c-Pr G-13 (1) 5-c-Pr
G-3 (1) 4-n-Bu G-13 (1) 5-n-Bu
G-3 (1) 4-i-Bu G-13 (1) 5-i-Bu
G-3 (1) 4-t-Bu G-13 (1) 5-t-Bu
G-3 (1) 4-F G-13 (1) 5-F
G-3 (1) 4-C1 G-13 (1) 5-C1
G-3 (1) 4-Br G-13 (1) 5-Br
G-3 (1) 4-CF3 G-13 (1) 5-CF3
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
133
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-3 (1) 4-HO G-13 (1) 5-HO
G-3 (1) 4-NEC G-13 (1) 5-NEC
G-3 (1) 4-I\TCCH2 G-13 (1) 5-I\TCCH2
G-3 (1) 4-(Me0) G-13 (1) 5-(Me0)
G-3 (1) 4-(MeOCH2) G-13 (1) 5-(MeOCH2)
G-3 (1) 4-(EtOCH2) G-13 (1) 5-(EtOCH2)
G-3 (1) 4-(CH(=0)) G-13 (1) 5-(CH(=0))
G-3 (1) 4-(HOC(=0)) G-13 (1) 5-(HOC(=0))
G-3 (1) 4-(Me0C(=0)) G-13 (1) 5-(Me0C(=0))
G-3 (1) 4-(Et0C(=0)) G-13 (1) 5-(Et0C(=0))
G-3 (1) 4-(i-PrOC(=0)) G-13 (1) 5-(i-PrOC(=0))
G-3 (1) 4-(n-PrOC(=0)) G-13 (1) 5-(n-PrOC(=0))
G-3 (1) 4-(BuOC(=0)) G-13 (1) 5-(BuOC(=0))
G-3 (1) 4-(i-BuOC(=0)) G-13 (1) 5-(i-BuOC(=0))
G-3 (1) 4-(t-BuOC(=0)) G-13 (1) 5-(t-BuOC(=0))
G-3 (1) 4-(CF3CH20C(=0) G-13 (1) 5-(CF3CH20C(=0)
G-3 (1) 4-(CH2=CHOC(=0)) G-13 (1) 5-(CH2=CHOC(=0))
G-3 (1) 4-(CH2=CHCH20C(=0)) G-13 (1) 5-(CH2=CHCH20C(=0))
G-3 (1) 4-(CH2=CBrCH20C(=0)) G-13 (1) 5-(CH2=CBrCH20C(=0))
G-3 (1) 4-(CH2=CHCF20C(=0)) G-13 (1) 5-(CH2=CHCF20C(=0))
G-3 (1) 4-(Me2C=CHCH20C(=0)) G-13 (1) 5-(Me2C=CHCH20C(=0))
G-3 (1) 4-(CH2=C(Me)CH20C(=0)) G-13 (1) 5-(CH2=C(Me)CH20C(=0))
G-3 (1) 4-(CHCCH20C(=0)) G-13 (1) 5-(CHCCH20C(=0))
G-3 (1) 4-(NCCH20C(=0)) G-13 (1) 5-(NCCH20C(=0))
G-3 (1) 4-(MeNHC(=0)) G-13 (1) 5-(MeNHC(=0))
G-3 (1) 4-(Me2NC(=0)) G-13 (1) 5-(Me2NC(=0))
G-3 (1) 4-(MeNHC(=0)) G-13 (1) 5-(MeNHC(=0))
G-3 (1) 4-(EtNHC(=0)) G-13 (1) 5-(EtNHC(=0))
G-3 (1) 4-(PrNHC(=0)) G-13 (1) 5-(PrNHC(=0))
G-3 (1) 4-(i-PrNHC(=0)) G-13 (1) 5-(i-PrNHC(=0))
G-3 (1) 4-(BuNHC(=0)) G-13 (1) 5-(BuNHC(=0))
G-3 (1) 4-(t-BuNHC(=0)) G-13 (1) 5-(t-BuNHC(=0))
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
134
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-3 (1) 4-(i-BuNHC(=0)) G-13 (1) 5-(i-BuNHC(=0))
G-3 (1) 4-(CF3CH2NHC(=0)) G-13 (1) 5-(CF3CH2NHC(=0))
G-3 (1) 4-(c-PrCH2NHC(=0)) G-13 (1) 5-(c-PrCH2NHC(=0))
G-3 (1) 4-(MeOCH2NHC(=0)) G-13 (1) 5-(MeOCH2NHC(=0))
G-3 (1) 4-(MeOCH2CH2NHC(=0)) G-13 (1) 5-(MeOCH2CH2NHC(=0))
G-3 (1) 4-(CH2=CHCH2NHC(=0)) G-13 (1) 5-(CH2=CHCH2NHC(=0))
G-3 (1) 4-(1\TCCH2NHC(=0)) G-13 (1) 5-(1\TCCH2NHC(=0))
G-3 (1) 4-(OH-N=CH) G-13 (1) 5-(OH-N=CH)
G-3 (1) 4-(Me2NN=CH) G-13 (1) 5-(Me2NN=CH)
G-3 (1) 4-(Me0C(=0)NHN=CH) G-13 (1) 5-(Me0C(=0)NHN=CH)
G-3 (1) 4-(OHC(=0)CH2ON=CH) G-13 (1) 5-(OHC(=0)CH2ON=CH)
G-9(1) G-17(1)
G-9 (1) 3-Me G-17 (1) 4-Me
G-9(1) 3-Et G-17(1) 4-Et
G-9(1) 3-n-Pr G-17(1) 4-n-Pr
G-9 (1) 3-i-Pr G-17 (1) 4-i-Pr
G-9 (1) 3-c-Pr G-17 (1) 4-c-Pr
G-9 (1) 3-n-Bu G-17 (1) 4-n-Bu
G-9 (1) 3-i-Bu G-17 (1) 4-i-Bu
G-9 (1) 3-t-Bu G-17 (1) 4-t-Bu
G-9(1) 3-F G-17(1) 4-F
G-9 (1) 3-C1 G-17 (1) 4-C1
G-9(1) 3-Br G-17(1) 4-Br
G-9 (1) 3-CF3 G-17 (1) 4-CF3
G-9(1) 3-HO G-17(1) 4-HO
G-9 (1) 3-NEC G-17 (1) 4-NEC
G-9 (1) 3-I\TCCH2 G-17 (1) 4-I\TCCH2
G-9 (1) 3-(Me0) G-17 (1) 4-(Me0)
G-9 (1) 3-(MeOCH2) G-17 (1) 4-(MeOCH2)
G-9 (1) 3-(EtOCH2) G-17 (1) 4-(EtOCH2)
G-9 (1) 3-(CH(=0)) G-17 (1) 4-(CH(=0))
G-9 (1) 3-(HOC(=0)) G-17 (1) 4-(HOC(=0))
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
135
J is J-1, L is CH2 and Z is a direct bond. J is J-1, L is CH2 and Z is a
direct bond.
G (R13)x G (R13)x
G-9 (1) 3-(Me0C(=0)) G-17 (1) 4-(Me0C(=0))
G-9 (1) 3-(Et0C(=0)) G-17 (1) 4-(Et0C(=0))
G-9 (1) 3-(i-PrOC(=0)) G-17 (1) 4-(i-PrOC(=0))
G-9 (1) 3-(n-PrOC(=0)) G-17 (1) 4-(n-PrOC(=0))
G-9 (1) 3-(BuOC(=0)) G-17 (1) 4-(BuOC(=0))
G-9 (1) 3-(i-BuOC(=0)) G-17 (1) 4-(i-BuOC(=0))
G-9 (1) 3-(t-BuOC(=0)) G-17 (1) 4-(t-BuOC(=0))
G-9 (1) 3-(CF3CH20C(=0) G-17 (1) 4-(CF3CH20C(=0)
G-9 (1) 3-(CH2=CHOC(=0)) G-17 (1) 4-(CH2=CHOC(=0))
G-9 (1) 3-(CH2=CHCH20C(=0)) G-17 (1) 4-(CH2=CHCH20C(=0))
G-9 (1) 3-(CH2=CBrCH20C(=0)) G-17 (1) 4-(CH2=CBrCH20C(=0))
G-9 (1) 3-(CH2=CHCF20C(=0)) G-17 (1) 4-(CH2=CHCF20C(=0))
G-9 (1) 3-(Me2C=CHCH20C(=0)) G-17 (1) 4-(Me2C=CHCH20C(=0))
G-9 (1) 3-(CH2=C(Me)CH20C(=0)) G-17 (1) 4-(CH2=C(Me)CH20C(=0))
G-9 (1) 3-(CHCCH20C(=0)) G-17 (1) 4-(CHCCH20C(=0))
G-9 (1) 3-(NCCH20C(=0)) G-17 (1) 4-(NCCH20C(=0))
G-9 (1) 3-(MeNHC(=0)) G-17 (1) 4-(MeNHC(=0))
G-9 (1) 3-(Me2NC(=0)) G-17 (1) 4-(Me2NC(=0))
G-9 (1) 3-(MeNHC(=0)) G-17 (1) 4-(MeNHC(=0))
G-9 (1) 3-(EtNHC(=0)) G-17 (1) 4-(EtNHC(=0))
G-9 (1) 3-(PrNHC(=0)) G-17 (1) 4-(PrNHC(=0))
G-9 (1) 3-(i-PrNHC(=0)) G-17 (1) 4-(i-PrNHC(=0))
G-9 (1) 3-(BuNHC(=0)) G-17 (1) 4-(BuNHC(=0))
G-9 (1) 3-(t-BuNHC(=0)) G-17 (1) 4-(t-BuNHC(=0))
G-9 (1) 3-(i-BuNHC(=0)) G-17 (1) 4-(i-BuNHC(=0))
G-9 (1) 3-(CF3CH2NHC(=0)) G-17 (1) 4-(CF3CH2NHC(=0))
G-9 (1) 3-(c-PrCH2NHC(=0)) G-17 (1) 4-(c-PrCH2NHC(=0))
G-9 (1) 3-(MeOCH2NHC(=0)) G-17 (1) 4-(MeOCH2NHC(=0))
G-9 (1) 3-(MeOCH2CH2NHC(=0)) G-17 (1) 4-(MeOCH2CH2NHC(=0))
G-9 (1) 3-(CH2=CHCH2NHC(=0)) G-17 (1) 4-(CH2=CHCH2NHC(=0))
G-9 (1) 3-(NCCH2NHC(=0)) G-17 (1) 4-(NCCH2NHC(=0))
G-9 (1) 3-(OH-N=CH) G-17 (1) 4-(OH-N=CH)
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
136
J is J-1, L is CH2 and Z is a direct bond.
J is J-1, L is CH2 and Z is a direct bond.
(R13) G (R13)x
G-9 (1) 3-(Me2NN=CH) G-17 (1) 4-(Me2NN=CH)
G-9 (1) 3-(Me0C(=0)NHN=CH) G-17 (1) 4-(Me0C(=0)NHN=CH)
G-9 (1) 3-(OHC(=0)CH2ON=CH) G-17 (1) 4-(OHC(=0)CH2ON=CH)
The present disclosure also includes Tables 1B through 48B, each of which is
constructed
the same as Table 2 above, except that the row heading in Table 2 (i.e. "J is
J-1, L is CH2, and Z
is a direct bond") is replaced with the respective row headings shown below.
Table Row Heading Table Row Heading
1B J is J-1, L is CH2CH2 and Z is a direct bond. 25B J is J-10, L is
CH2 and Z is a direct bond.
2B J is J-1, L is CH2(Me) and Z is a direct bond. 26B J is J-10, L is
CH2CH2 and Z is a direct bond.
3B J is J-1, L is (CH2)3 and Z is a direct bond. 27B J is J-10, L is
CH2(Me) and Z is a direct bond.
4B J is J-1, L is CH2 and Z is 0. 28B J is J-10, L is (CH2)3 and Z
is a direct bond.
5B J is J-2, L is CH2 and Z is a direct bond. 29B J is J-10, L is CH2
and Z is O.
6B J is J-2, L is CH2CH2 and Z is a direct bond. 30B J is J-14, L is
CH2 and Z is a direct bond.
7B J is J-2, L is CH2(Me) and Z is a direct bond. 31B J is J-14, L is
CH2CH2 and Z is a direct bond.
8B J is J-2, L is (CH2)3 and Z is a direct bond. 32B J is J-14, L is
CH2(Me) and Z is a direct bond.
9B J is J-2, L is CH2 and Z is 0. 33B J is J-14, L is (CH2)3 and Z
is a direct bond.
10B J is J-6, L is CH2 and Z is a direct bond.
34B J is J-14, L is CH2 and Z is O.
11B J is J-6, L is CH2CH2 and Z is a direct
bond. 35B J is J-3, L is CH2 and Z is a direct bond.
12B J is J-6, L is CH2(Me) and Z is a direct
bond. 36B J is J-3, L is CH2CH2 and Z is a direct bond.
13B J is J-6, L is (CH2)3 and Z is a direct
bond. 37B J is J-3, L is CH2(Me) and Z is a direct bond.
14B J is J-6, L is CH2 and Z is 0. 38B J
is J-3, L is (CH2)3 and Z is a direct bond.
15B J is J-7, L is CH2 and Z is a direct bond.
39B J is J-3, L is CH2 and Z is 0.
16B J is J-7, L is CH2CH2 and Z is a direct
bond. 40B J is J-4, L is CH2 and Z is a direct bond.
17B J is J-7, L is CH2(Me) and Z is a direct
bond. 41B J is J-4, L is CH2CH2 and Z is a direct bond.
18B J is J-7, L is (CH2)3 and Z is a direct
bond. 42B J is J-4, L is CH2(Me) and Z is a direct bond.
19B J is J-7, L is CH2 and Z is 0. 43B J
is J-4, L is (CH2)3 and Z is a direct bond.
20B J is J-8, L is CH2 and Z is a direct bond.
44B J is J-4, L is CH2 and Z is 0.
21B J is J-8, L is CH2CH2 and Z is a direct
bond. 45B J is J-5, L is CH2 and Z is a direct bond.
22B J is J-8, L is CH2(Me) and Z is a direct
bond. 46B J is J-5, L is CH2CH2 and Z is a direct bond.
23B J is J-8, L is (CH2)3 and Z is a direct
bond. 47B J is J-5, L is CH2(Me) and Z is a direct bond.
24B J is J-8, L is CH2 and Z is 0. 48B J
is J-5, L is (CH2)3 and Z is a direct bond.
Formulation/Utility
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
137
A compound of Formula 1 of this invention (including N-oxides and salts
thereof), or a
mixture (i.e. composition) comprising the compound with at least one
additional fungicidal
compound as described in the Summary of the Invention, will generally be used
as a fungicidal
active ingredient in a composition, i.e. formulation, with at least one
additional component
selected from the group consisting of surfactants, solid diluents and liquid
diluents, which serve
as a carrier. The formulation or composition ingredients are selected to be
consistent with the
physical properties of the active ingredient, mode of application and
environmental factors such
as soil type, moisture and temperature.
The mixtures of component (a) (i.e. at least one compound of Formula 1, N-
oxides, or salts
thereof) with component (b) (e.g., selected from (b 1) to (b54) and salts
thereof as described above)
and/or one or more other biologically active compound or agent (i.e.
insecticides, other fungicides,
nematocides, acaricides, herbicides and other biological agents) can be
formulated in a number of
ways, including:
(i) component (a), component (b) and/or one or more other biologically
active compounds
or agents can be formulated separately and applied separately or applied
simultaneously
in an appropriate weight ratio, e.g., as a tank mix; or
(ii) component (a), component (b) and/or one or more other biologically active
compounds
or agents can be formulated together in the proper weight ratio.
Useful formulations include both liquid and solid compositions. Liquid
compositions
include solutions (including emulsifiable concentrates), suspensions,
emulsions (including
microemulsions, oil-in-water emulsions, flowable concentrates and/or
suspoemulsions) and the
like, which optionally can be thickened into gels. The general types of
aqueous liquid
compositions are soluble concentrate, suspension concentrate, capsule
suspension, concentrated
emulsion, microemulsion, oil-in-water emulsion, flowable concentrate and
suspoemulsion. The
general types of nonaqueous liquid compositions are emulsifiable concentrate,
microemulsifiable
concentrate, dispersible concentrate and oil dispersion.
The general types of solid compositions are dusts, powders, granules, pellets,
prills,
pastilles, tablets, filled films (including seed coatings) and the like, which
can be water-dispersible
("wettable") or water-soluble. Films and coatings formed from film-forming
solutions or
flowable suspensions are particularly useful for seed treatment. Active
ingredient can be
(micro)encapsulated and further formed into a suspension or solid formulation;
alternatively the
entire formulation of active ingredient can be encapsulated (or "overcoated").
Encapsulation can
control or delay release of the active ingredient. An emulsifiable granule
combines the advantages
of both an emulsifiable concentrate formulation and a dry granular
formulation. High-strength
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
138
compositions are primarily used as intermediates for further formulation.
Of note is a composition embodiment wherein granules of a solid composition
comprising
a compound of Formula 1 (or an N-oxide or salt thereof) is mixed with granules
of a solid
composition comprising component (b). These mixtures can be further mixed with
granules
comprising additional agricultural protectants. Alternatively, two or more
agricultural protectants
(e.g., a component (a) (Formula 1) compound, a component (b) compound, an
agricultural
protectant other than component (a) or (b)) can be combined in the solid
composition of one set
of granules, which is then mixed with one or more sets of granules of solid
compositions
comprising one or more additional agricultural protectants. These granule
mixtures can be in
accordance with the general granule mixture disclosure of PCT Patent
Publication WO 94/24861
or more preferably the homogeneous granule mixture teaching of U.S. Patent
6,022,552.
Sprayable formulations are typically extended in a suitable medium before
spraying. Such
liquid and solid formulations are formulated to be readily diluted in the
spray medium, usually
water, but occasionally another suitable medium like an aromatic or paraffinic
hydrocarbon or
vegetable oil. Spray volumes can range from about one to several thousand
liters per hectare, but
more typically are in the range from about ten to several hundred liters per
hectare. Sprayable
formulations can be tank mixed with water or another suitable medium for
foliar treatment by
aerial or ground application, or for application to the growing medium of the
plant. Liquid and
dry formulations can be metered directly into drip irrigation systems or
metered into the furrow
during planting. Liquid and solid formulations can be applied onto seeds of
crops and other
desirable vegetation as seed treatments before planting to protect developing
roots and other
subterranean plant parts and/or foliage through systemic uptake.
The formulations will typically contain effective amounts of active
ingredient, diluent and
surfactant within the following approximate ranges which add up to 100 percent
by weight.
Weight Percent
Active
Ingredient Diluent Surfactant
Water-Dispersible and Water- 0.001-90 0-99.999 0-15
soluble Granules, Tablets and
Powders
Oil Dispersions, Suspensions, 1-50 40-99 0-50
Emulsions, Solutions
(including Emulsifiable
Concentrates)
Dusts 1-25 70-99 0-5
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
139
Granules and Pellets 0.001-95 5-99.999 0-15
High Strength Compositions 90-99 0-10 0-2
Solid diluents include, for example, clays such as bentonite, montmorillonite,
attapulgite
and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin,
sugars (e.g., lactose,
sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate,
sodium carbonate and
bicarbonate, and sodium sulfate. Typical solid diluents are described in
Watkins et al., Handbook
of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell,
New Jersey.
Liquid diluents include, for example, water, N,N-dimethylalkanamides (e.g.,
N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones
(e.g.,
N-methylpyrrolidinone), alkyl phosphates (e.g., triethyl phosphate), ethylene
glycol, triethylene
glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene
carbonate,
butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins,
isoparaffins),
alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol,
aromatic hydrocarbons,
dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as
cyclohexanone,
2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as
isoamyl acetate,
hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate
and isobornyl acetate,
other esters such as alkylated lactate esters, dibasic esters, alkyl and aryl
benzoates and y-
butyrolactone, and alcohols, which can be linear, branched, saturated or
unsaturated, such as
methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol,
n-hexanol, 2-
ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl
alcohol, lauryl alcohol,
tridecyl alcohol, ley' alcohol, cyclohexanol, tetrahydrofurfuryl alcohol,
diacetone alcohol, cresol
and benzyl alcohol. Liquid diluents also include glycerol esters of saturated
and unsaturated fatty
acids (typically C6¨C22), such as plant seed and fruit oils (e.g., oils of
olive, castor, linseed,
sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed,
soybean, rapeseed,
coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow,
lard, cod liver oil,
fish oil), and mixtures thereof. Liquid diluents also include alkylated fatty
acids (e.g., methylated,
ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of
glycerol esters from
plant and animal sources, and can be purified by distillation. Typical liquid
diluents are described
in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.
The solid and liquid compositions of the present invention often include one
or more
surfactants. When added to a liquid, surfactants (also known as "surface-
active agents") generally
modify, most often reduce, the surface tension of the liquid. Depending on the
nature of the
hydrophilic and lipophilic groups in a surfactant molecule, surfactants can be
useful as wetting
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
140
agents, dispersants, emulsifiers or defoaming agents.
Surfactants can be classified as nonionic, anionic or cationic. Nonionic
surfactants useful
for the present compositions include, but are not limited to: alcohol
alkoxylates such as alcohol
alkoxylates based on natural and synthetic alcohols (which may be branched or
linear) and
prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide
or mixtures
thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides;
alkoxylated
triglycerides such as ethoxylated soybean, castor and rapeseed oils;
alkylphenol alkoxylates such
as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol
ethoxylates and dodecyl
phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene
oxide, butylene
oxide or mixtures thereof); block polymers prepared from ethylene oxide or
propylene oxide and
reverse block polymers where the terminal blocks are prepared from propylene
oxide; ethoxylated
fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters;
ethoxylated tristyrylphenol
(including those prepared from ethylene oxide, propylene oxide, butylene oxide
or mixtures
thereof); fatty acid esters, glycerol esters, lanolin-based derivatives,
polyethoxylate esters such as
polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty
acid esters and
polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as
sorbitan esters;
polymeric surfactants such as random copolymers, block copolymers, alkyd peg
(polyethylene
glycol) resins, graft or comb polymers and star polymers; polyethylene glycols
(pegs);
polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-
derivatives such as
sucrose esters, alkyl polyglycosides; alkyl polysaccharides; and glucamides
such as mixtures of
octyl-N-methylglucamide and decyl-N-methylglucamide (e.g., products is
obtainable under the
Synergen GA name from Clariant).
Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic
acids and their
salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate
derivatives; lignin and
lignin derivatives such as lignosulfonates; maleic or succinic acids or their
anhydrides; olefin
sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates,
phosphate esters of
alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates;
protein-based
surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and
sulfonates of oils and
fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of
alcohols; sulfates of
ethoxylated alcohols; sulfonates of amines and amides such as N,N-
alkyltaurates; sulfonates of
benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates
of condensed
naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of
fractionated
petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives such
as dialkyl
sulfosuccinate salts.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
141
Useful cationic surfactants include, but are not limited to: amides and
ethoxylated amides;
amines such as N-alkyl propanediamines, tripropylenetriamines and
dipropylenetetramines, and
ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared
from the amines
and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof);
amine salts such as
amine acetates and diamine salts; quaternary ammonium salts such as quaternary
salts,
ethoxylated quaternary salts and diquaternary salts; and amine oxides such as
alkyldimethylamine
oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
Also useful for the present compositions are mixtures of nonionic and anionic
surfactants
or mixtures of nonionic and cationic surfactants. Nonionic, anionic and
cationic surfactants and
.. their recommended uses are disclosed in a variety of published references
including
McCutcheon's Emulsifiers and Detergents, annual American and International
Editions published
by McCutcheon' s Division, The Manufacturing Confectioner Publishing Co.;
Sisely and Wood,
Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York,
1964; and A. S.
Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley
and Sons, New
York, 1987.
Compositions of this invention may also contain formulation auxiliaries and
additives,
known to those skilled in the art as formulation aids (some of which may be
considered to also
function as solid diluents, liquid diluents or surfactants). Such formulation
auxiliaries and
additives may control: pH (buffers), foaming during processing (antifoams such
polyorganosiloxanes), sedimentation of active ingredients (suspending agents),
viscosity
(thixotropic thickeners), in-container microbial growth (antimicrobials),
product freezing
(antifreezes), color (dyes/pigment dispersions), wash-off (film formers or
stickers), evaporation
(evaporation retardants), and other formulation attributes. Film formers
include, for example,
polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl
acetate copolymer,
polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of
formulation
auxiliaries and additives include those listed in McCutcheon's Volume 2:
Functional Materials,
annual International and North American editions published by McCutcheon' s
Division, The
Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.
The compound of Formula 1 and any other active ingredients are typically
incorporated into
the present compositions by dissolving the active ingredient in a solvent or
by grinding in a liquid
or dry diluent. Solutions, including emulsifiable concentrates, can be
prepared by simply mixing
the ingredients. If the solvent of a liquid composition intended for use as an
emulsifiable
concentrate is water-immiscible, an emulsifier is typically added to emulsify
the active-containing
solvent upon dilution with water. Active ingredient slurries, with particle
diameters of up to 2,000
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
142
[tm can be wet milled using media mills to obtain particles with average
diameters below 3 [tm.
Aqueous slurries can be made into finished suspension concentrates (see, for
example, U.S.
3,060,084) or further processed by spray drying to form water-dispersible
granules. Dry
formulations usually require dry milling processes, which produce average
particle diameters in
the 2 to 10 [tm range. Dusts and powders can be prepared by blending and
usually grinding (such
as with a hammer mill or fluid-energy mill). Granules and pellets can be
prepared by spraying
the active material upon preformed granular carriers or by agglomeration
techniques. See
Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48,
Perry's
Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pp 8-57
and following,
and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-
dispersible
and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S.
3,920,442 and
DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S.
5,232,701 and U.S.
5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.
One embodiment of the present invention relates to a method for controlling
fungal
pathogens, comprising diluting the fungicidal composition of the present
invention (a compound
of Formula 1 formulated with surfactants, solid diluents and liquid diluents
or a formulated
mixture of a compound of Formula 1 and at least one other fungicide) with
water, and optionally
adding an adjuvant to form a diluted composition, and contacting the fungal
pathogen or its
environment with an effective amount of said diluted composition.
Although a spray composition formed by diluting with water a sufficient
concentration of
the present fungicidal composition can provide sufficient efficacy for
controlling fungal
pathogens, separately formulated adjuvant products can also be added to spray
tank mixtures.
These additional adjuvants are commonly known as "spray adjuvants" or "tank-
mix adjuvants",
and include any substance mixed in a spray tank to improve the performance of
a pesticide or alter
the physical properties of the spray mixture. Adjuvants can be anionic or
nonionic surfactants,
emulsifying agents, petroleum-based crop oils, crop-derived seed oils,
acidifiers, buffers,
thickeners or defoaming agents. Adjuvants are used to enhancing efficacy
(e.g., biological
availability, adhesion, penetration, uniformity of coverage and durability of
protection), or
minimizing or eliminating spray application problems associated with
incompatibility, foaming,
drift, evaporation, volatilization and degradation. To obtain optimal
performance, adjuvants are
selected with regard to the properties of the active ingredient, formulation
and target (e.g., crops,
insect pests).
The amount of adjuvants added to spray mixtures is generally in the range of
about 0.1 %
to 2.5% by volume. The application rates of adjuvants added to spray mixtures
are typically
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
143
between about 1 to 5 L per hectare. Representative examples of spray adjuvants
include: Adigor
(Syngenta) 47% methylated rapeseed oil in liquid hydrocarbons, Silwet (Helena
Chemical
Company) polyalkyleneoxide modified heptamethyltrisiloxane and Assist (BASF)
17%
surfactant blend in 83% paraffin based mineral oil.
One method of seed treatment is by spraying or dusting the seed with a
compound of the
invention (i.e. as a formulated composition) before sowing the seeds.
Compositions formulated
for seed treatment generally comprise a film former or adhesive agent.
Therefore typically a seed
coating composition of the present invention comprises a biologically
effective amount of a
compound of Formula 1 and a film former or adhesive agent. Seeds can be coated
by spraying a
flowable suspension concentrate directly into a tumbling bed of seeds and then
drying the seeds.
Alternatively, other formulation types such as wetted powders, solutions,
suspoemulsions,
emulsifiable concentrates and emulsions in water can be sprayed on the seed.
This process is
particularly useful for applying film coatings on seeds. Various coating
machines and processes
are available to one skilled in the art. Suitable processes include those
listed in P. Kosters et al.,
Seed Treatment: Progress and Prospects, 1994 BCPC Mongraph No. 57, and
references listed
therein.
For further information regarding the art of formulation, see T. S. Woods,
"The
Formulator's Toolbox ¨ Product Forms for Modern Agriculture" in Pesticide
Chemistry and
Bioscience, The Food¨Environment Challenge, T. Brooks and T. R. Roberts, Eds.,
Proceedings
of the 9th International Congress on Pesticide Chemistry, The Royal Society of
Chemistry,
Cambridge, 1999, pp. 120-133. Also see U.S. 3,235,361, Col. 6, line 16 through
Col. 7, line 19
and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62
and Examples 8, 12,
15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S.
2,891,855, Col. 3,
line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a
Science, John
Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance et al., Weed Control
Handbook, 8th Ed.,
Blackwell Scientific Publications, Oxford, 1989; and Developments in
formulation technology,
PJB Publications, Richmond, UK, 2000.
In the following Examples, all percentages are by weight and all formulations
are prepared
in conventional ways. Active ingredient refers to the compounds in Index
Tables A-L disclosed
herein. Without further elaboration, it is believed that one skilled in the
art using the preceding
description can utilize the present invention to its fullest extent. The
following Examples are,
therefore, to be constructed as merely illustrative, and not limiting of the
disclosure in any way
whatsoever.
Example A
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
144
High Strength Concentrate
Compound 263 98.5%
silica aerogel 0.5%
synthetic amorphous fine silica 1.0%
Example B
Wettable Powder
Compound 330 65.0%
dodecylphenol polyethylene glycol ether 2.0%
sodium ligninsulfonate 4.0%
sodium silicoaluminate 6.0%
montmorillonite (calcined) 23.0%
Example C
Granule
Compound 64 10.0%
attapulgite granules (low volatile matter, 0.71/0.30 mm; 90.0%
U.S.S. No. 25-50 sieves)
Example D
Extruded Pellet
Compound 32 25.0%
anhydrous sodium sulfate 10.0%
crude calcium ligninsulfonate 5.0%
sodium alkylnaphthalenesulfonate 1.0%
calcium/magnesium bentonite 59.0%
Example E
Emulsifiable Concentrate
Compound 64 10.0%
polyoxyethylene sorbitol hexoleate 20.0%
C6¨C10 fatty acid methyl ester 70.0%
Example F
Microemulsion
Compound 331 5.0%
polyvinylpyrrolidone-vinyl acetate copolymer 30.0%
alkylpolyglycoside 30.0%
glyceryl monooleate 15.0%
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
145
water 20.0%
Example G
Seed Treatment
Compound 297 20.00%
polyvinylpyrrolidone-vinyl acetate copolymer 5.00%
montan acid wax 5.00%
calcium ligninsulfonate 1.00%
polyoxyethylene/polyoxypropylene block copolymers 1.00%
stearyl alcohol (POE 20) 2.00%
polyorganosilane 0.20%
colorant red dye 0.05%
water 65.75%
Example H
Fertilizer Stick
Compound 126 2.50%
pyrrolidone-styrene copolymer 4.80%
tristyrylphenyl 16-ethoxylate 2.30%
talc 0.80%
corn starch 5.00%
slow-release fertilizer 36.00%
kaolin 38.00%
water 10.60%
Example I
Suspension Concentrate
Compound 163 35%
butyl polyoxyethylene/polypropylene block copolymer 4.0%
stearic acid/polyethylene glycol copolymer 1.0%
styrene acrylic polymer 1.0%
xanthan gum 0.1%
propylene glycol 5.0%
silicone based defoamer 0.1%
1,2-benzisothiazolin-3 -one 0.1%
water 53.7%
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
146
Example J
Emulsion in Water
Compound 71
10.0%
butyl polyoxyethylene/polypropylene block copolymer
4.0%
stearic acid/polyethylene glycol copolymer
1.0%
styrene acrylic polymer
1.0%
xanthan gum
0.1%
propylene glycol
5.0%
silicone based defoamer
0.1%
1,2-benzisothiazolin-3-one
0.1%
aromatic petroleum based hydrocarbon
20.0
water
58.7%
Example K
Oil Dispersion
Compound 229 25%
polyoxyethylene sorbitol hexaoleate 15%
organically modified bentonite clay
2.5%
fatty acid methyl ester
57.5%
Example L
Suspoemulsion
Compound 127
10.0%
imidacloprid
5.0%
butyl polyoxyethylene/polypropylene block copolymer
4.0%
stearic acid/polyethylene glycol copolymer
1.0%
styrene acrylic polymer
1.0%
xanthan gum
0.1%
propylene glycol
5.0%
silicone based defoamer
0.1%
1,2-benzisothiazolin-3-one
0.1%
aromatic petroleum based hydrocarbon
20.0%
water
53.7%
Water-soluble and water-dispersible formulations are typically diluted with
water to form
aqueous compositions before application. Aqueous compositions for direct
applications to the
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
147
plant or portion thereof (e.g., spray tank compositions) typically contain at
least about 1 ppm or
more (e.g., from 1 ppm to 100 ppm) of the compound(s) of this invention.
Seed is normally treated at a rate of from about 0.001 g (more typically about
0.1 g) to about
g per kilogram of seed (i.e. from about 0.0001 to 1% by weight of the seed
before treatment).
5
A flowable suspension formulated for seed treatment typically comprises from
about 0.5 to about
70% of the active ingredient, from about 0.5 to about 30% of a film-forming
adhesive, from about
0.5 to about 20% of a dispersing agent, from 0 to about 5% of a thickener,
from 0 to about 5% of
a pigment and/or dye, from 0 to about 2% of an antifoaming agent, from 0 to
about 1% of a
preservative, and from 0 to about 75% of a volatile liquid diluent.
10
The compositions of this invention are useful as plant disease control agents.
The present
invention therefore further comprises a method for controlling plant diseases
caused by fungal
plant pathogens comprising applying to the plant or portion thereof to be
protected, or to the plant
seed to be protected, an effective amount of a compound of the invention or a
fungicidal
composition containing said compound. The compounds and/or compositions of
this invention
provide control of diseases caused by a broad spectrum of fungal plant
pathogens in the
Ascomycota, Basidiomycota, Zygomycota phyla, and the fungal-like Oomycota
class. They are
effective in controlling a broad spectrum of plant diseases, particularly
foliar pathogens of
ornamental, turf, vegetable, field, cereal, and fruit crops. These pathogens
include but are not
limited to those listed in Table 1-1. For Ascomycetes and Basidiomycetes,
names for both the
sexual/teleomorph/perfect stage as well as names for the
asexual/anamorph/imperfect stage (in
parentheses) are listed where known. Synonymous names for pathogens are
indicated by an equal
sign. For example, the sexual/teleomorph/perfect stage name Phaeosphaeria
nodorum is followed
by the corresponding asexual/anamorph/imperfect stage name Stagnospora nodorum
and the
synonymous older name Septoria nodorum.
Table 1-1
Ascomycetes in the order Pleosporales including Altemaria solani, A. altemata
and A. brassicae,
Guignardia bidwellii, Venturia inaequalis, Pyrenophora tritici-repentis
(Dreschlera tritici-repentis =
Helminthosporium tritici-repentis) and Pyrenophora teres (Dreschlera teres =
Helminthosporium
teres), Cotynespora cassiicola, Phaeosphaeria nodorum (Stagonospora nodorum =
Septoria
nodorum), Cochliobolus carbonum and C. heterostrophus, Leptosphaeria biglobosa
and L.
maculans;
Ascomycetes in the order Mycosphaerellales including Mycosphaerella
graminicola (Zymoseptoria
tritici = Septoria tritici), M. berkeleyi (Cercosporidium personatum), M.
arachidis (Cercospora
arachidicola), Passalora sojina (Cercospora sojina), Cercospora zeae-maydis
and C. beticola;
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
148
Ascomycetes in the order Erysiphales (the powdery mildews) such as Blumeria
graminis f. sp. tritici
and Blumeria graminis tsp. hordei, Eiysiphe polygoni, E. necator (= Uncinula
necator),
Podosphaera fuliginea (= Sphaerotheca fuliginea), and Podosphaera leucotricha
(= Sphaerotheca
fiiliginea);
Ascomycetes in the order Helotiales such as Botiyotinia fuckeliana (Bonytis
cinerea), Oculimacula
yallundae (= Tapesia yallundae; anamorph Helgardia herpotrichoides =
Pseudocercosporella
herpetrichoides), Monilinia fructicola, Sclerotinia sclerotiorum, Sclerotinia
minor, and Sclerotinia
homoeocarpa;
Ascomycetes in the order Hypocreales such as Gibe rella zeae (Fusarium
graminearum), G.
monoliformis (Fusarium moniliforme), Fusarium solani and Verticillium dahliae;
Ascomycetes in the order Eurotiales such as Aspergillus flavus and A.
parasiticus;
Ascomycetes in the order Diaporthales such as Ciyptosphorella viticola (=
Phomopsis viticola),
Phomopsis longicolla, and Diaporthe phaseolorum;
Other Ascomycete pathogens including Magnaporthe grisea, Gaeumannomyces
graminis,
Rhynchosporium secalis, and anthracnose pathogens such as Glomerella acutata
(Colletotrichum
acutatum), G. graminicola (C. graminicola) and G. lagenaria (C. orbiculare);
Basidiomycetes in the order Urediniales (the rusts) including Puccinia
recondita, P. striiformis,
Puccinia hordei, P. graminis and P. arachidis), Hemileia vastatrix and
Phakopsora pachyrhizi;
Basidiomycetes in the order Ceratobasidiales such as Thanatophorum cucumeris
(Rhizoctonia solani)
and Ceratobasidium myzae-sativae (Rhizoctonia oryzae);
Basidiomycetes in the order Polyporales such as Athelia rolfsii (Sclerotium
rolfsii);
Basidiomycetes in the order Ustilaginales such as Ustilago maydis;
Zygomycetes in the order Mucorales such as Rhizopus stolonifer;
Oomycetes in the order Pythiales, including Phytophthora infestans, P.
megasperma, P. parasitica,
P. sojae, P. cinnamomi and P. capsici, and Pythium pathogens such as Pythium
aphanidermatum, P.
graminicola, P. irregulare, P. ultimum and P. dissoticum;
Oomycetes in the order Peronosporales such as Plasmopara viticola, P.
halstedii, Peronospora
hyoscyami (=Peronospora tabacina), P. manshurica, Hyaloperonospora parasitica
(=Peronospora
parasitica), Pseudoperonospora cubensis and Bremia lactucae;
and other genera and species closely related to all of the above pathogens.
In addition to their fungicidal activity, the compositions or combinations
also have activity
against bacteria such as Erwinia arnylovora, Xanthornonas carnpestris,
Pseudornonas syringae,
and other related species. By controlling harmful microorganisms, the
compositions of this
invention are useful for improving (i.e. increasing) the ratio of beneficial
to harmful
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
149
microorganisms in contact with crop plants or their propagules (e.g., seeds,
corms, bulbs, tubers,
cuttings) or in the agronomic environment of the crop plants or their
propagules.
Compositions of this invention are useful in treating all plants, plant parts
and seeds. Plant
and seed varieties and cultivars can be obtained by conventional propagation
and breeding
methods or by genetic engineering methods. Genetically modified plants or
seeds (transgenic
plants or seeds) are those in which a heterologous gene (transgene) has been
stably integrated into
the plant's or seed's genome. A transgene that is defined by its particular
location in the plant
genome is called a transformation or transgenic event.
Genetically modified plant cultivars which can be treated according to the
invention include
those that are resistant against one or more biotic stresses (pests such as
nematodes, insects, mites,
fungi, etc.) or abiotic stresses (drought, cold temperature, soil salinity,
etc.), or that contain other
desirable characteristics. Plants can be genetically modified to exhibit
traits of, for example,
herbicide tolerance, insect-resistance, modified oil profiles or drought
tolerance.
Treatment of genetically modified plants and seeds with compounds of the
invention may
result in super-additive or enhanced effects. For example, reduction in
application rates,
broadening of the activity spectrum, increased tolerance to biotic/abiotic
stresses or enhanced
storage stability may be greater than expected from just simple additive
effects of the application
of compounds of the invention on genetically modified plants and seeds.
Compounds and compositions of this invention are useful in seed treatments for
protecting
.. seeds from plant diseases. In the context of the present disclosure and
claims, treating a seed
means contacting the seed with a biologically effective amount of a compound
of this invention,
which is typically formulated as a composition of the invention. This seed
treatment protects the
seed from soil-borne disease pathogens and generally can also protect roots
and other plant parts
in contact with the soil of the seedling developing from the germinating seed.
The seed treatment
may also provide protection of foliage by translocation of the compound of
this invention or a
second active ingredient within the developing plant. Seed treatments can be
applied to all types
of seeds, including those from which plants genetically transformed to express
specialized traits
will germinate. Representative examples include those expressing proteins
toxic to invertebrate
pests, such as Bacillus thuringiensis toxin or those expressing herbicide
resistance such as
glyphosate acetyltransferase, which provides resistance to glyphosate. Seed
treatments with
compounds and compositions of this invention can also increase vigor of plants
growing from the
seed.
Compounds and compositions of this invention are particularly useful in seed
treatment for
crops including, but not limited to, maize or corn, soybeans, cotton, cereal
(e.g., wheat, oats,
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
150
barley, rye and rice), potatoes, vegetables and oilseed rape.
Furthermore, the compounds and compositions of this invention are useful in
treating
postharvest diseases of fruits and vegetables caused by fungi, oomycetes and
bacteria. These
infections can occur before, during and after harvest. For example, infections
can occur before
harvest and then remain dormant until some point during ripening (e.g., host
begins tissue changes
in such a way that infection can progress or conditions become conducive for
disease
development); also infections can arise from surface wounds created by
mechanical or insect
injury. In this respect, the compositions of this invention can reduce losses
(i.e. losses resulting
from quantity and quality) due to postharvest diseases which may occur at any
time from harvest
to consumption. Treatment of postharvest diseases with compounds of the
invention can increase
the period of time during which perishable edible plant parts (e.g., fruits,
seeds, foliage, stems,
bulbs, tubers) can be stored refrigerated or un-refrigerated after harvest,
and remain edible and
free from noticeable or harmful degradation or contamination by fungi or other
microorganisms.
Treatment of edible plant parts before or after harvest with compounds of the
invention can also
decrease the formation of toxic metabolites of fungi or other microorganisms,
for example,
mycotoxins such as aflatoxins.
Plant disease control is ordinarily accomplished by applying an effective
amount of a
compound of this invention either pre- or post-infection, to the portion of
the plant to be protected
such as the roots, stems, foliage, fruits, seeds, tubers or bulbs, or to the
media (soil or sand) in
which the plants to be protected are growing. The compounds can also be
applied to seeds to
protect the seeds and seedlings developing from the seeds. The compounds can
also be applied
through irrigation water to treat plants. Control of postharvest pathogens
which infect the produce
before harvest is typically accomplished by field application of a compound of
this invention, and
in cases where infection occurs after harvest the compounds can be applied to
the harvested crop
as dips, sprays, fumigants, treated wraps and box liners.
The compounds and compositions of this invention can also be applied using an
unmanned
aerial vehicle (UAV) for the dispension of the compositions disclosed herein
over a planted area.
In some embodiments the planted area is a crop-containing area. In some
embodiments, the crop
is selected from a monocot or dicot. In some embodiments, the crop is selected
form rice, corn,
barley, sobean, wheat, vegetable, tobacco, tea tree, fruit tree and sugar
cane. In some
embodiments, the compositions disclosed herein are formulated for spraying at
an ultra-low
volume. Products applied by drones may use water or oil as the spray carrier.
Typical spray
volume (including product) used for drone applications globally. 5.0 liters/ha
¨ 100 liters/ha
(approximately 0.5-10 gpa). This includes the range of ultra low spray volume
(ULV) to low
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
151
spray volume (LV). Although not common there may be situations where even
lower spray
volumes could be used as low as 1.0 liter/ha (0.1 gpa).
Suitable rates of application (e.g., fungicidally effective amounts) of
component (a) (i.e. at
least one compound selected from compounds of Formula 1, N-oxides and salts
thereof) as well
as suitable rates of applicaton (e.g., biologically effective amounts,
fungicidally effective amounts
or insecticidally effective amounts) for the mixtures and compositions
comprising component (a)
according to this invention can be influenced by factors such as the plant
diseases to be controlled,
the plant species to be protected, the population structure of the pathogen to
be controlled, ambient
moisture and temperature and should be determined under actual use conditions.
One skilled in
the art can easily determine through simple experimentation the fungicidally
effective amount
necessary for the desired level of plant disease control. Foliage can normally
be protected when
treated at a rate of from less than about 1 g/ha to about 5,000 g/ha of active
ingredient. Seed and
seedlings can normally be protected when seed is treated at a rate of from
about 0.001 g (more
typically about 0.1 g) to about 10 g per kilogram of seed. One skilled in the
art can easily
determine through simple experimentation the application rates of component
(a), and mixtures
and compositions thereof, containing particular combinations of active
ingredients according to
this invention needed to provide the desired spectrum of plant protection and
control of plant
diseases and optionally other plant pests.
Compounds and compositions of the present invention may also be useful for
increasing
vigor of a crop plant. This method comprises contacting the crop plant (e.g.,
foliage, flowers, fruit
or roots) or the seed from which the crop plant is grown with a composition
comprising a
compound of Formula 1 in amount sufficient to achieve the desired plant vigor
effect (i.e.
biologically effective amount). Typically the compound of Formula 1 is applied
in a formulated
composition. Although the compound of Formula 1 is often applied directly to
the crop plant or
its seed, it can also be applied to the locus of the crop plant, i.e. the
environment of the crop plant,
particularly the portion of the environment in close enough proximity to allow
the compound of
Formula 1 to migrate to the crop plant. The locus relevant to this method most
commonly
comprises the growth medium (i.e. medium providing nutrients to the plant),
typically soil in
which the plant is grown. Treatment of a crop plant to increase vigor of the
crop plant thus
comprises contacting the crop plant, the seed from which the crop plant is
grown or the locus of
the crop plant with a biologically effective amount of a compound of Formula
1.
Increased crop vigor can result in one or more of the following observed
effects: (a) optimal
crop establishment as demonstrated by excellent seed germination, crop
emergence and crop
stand; (b) enhanced crop growth as demonstrated by rapid and robust leaf
growth (e.g., measured
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
152
by leaf area index), plant height, number of tillers (e.g., for rice), root
mass and overall dry weight
of vegetative mass of the crop; (c) improved crop yields, as demonstrated by
time to flowering,
duration of flowering, number of flowers, total biomass accumulation (i.e.
yield quantity) and/or
fruit or grain grade marketability of produce (i.e. yield quality); (d)
enhanced ability of the crop
to withstand or prevent plant disease infections and arthropod, nematode or
mollusk pest
infestations; and (e) increased ability of the crop to withstand environmental
stresses such as
exposure to thermal extremes, suboptimal moisture or phytotoxic chemicals.
The compounds and compositions of the present invention may increase the vigor
of treated
plants compared to untreated plants by preventing and/or curing plant diseases
caused by fungal
plant pathogens in the environment of the plants. In the absence of such
control of plant diseases,
the diseases reduce plant vigor by consuming plant tissues or sap, or
transmiting plant pathogens
such as viruses. Even in the absence of fungal plant pathogens, the compounds
of the invention
may increase plant vigor by modifying metabolism of plants. Generally, the
vigor of a crop plant
will be most significantly increased by treating the plant with a compound of
the invention if the
plant is grown in a nonideal environment, i.e. an environment comprising one
or more aspects
adverse to the plant achieving the full genetic potential it would exhibit in
an ideal environment.
Of note is a method for increasing vigor of a crop plant wherein the crop
plant is grown in
an environment comprising plant diseases caused by fungal plant pathogens.
Also of note is a
method for increasing vigor of a crop plant wherein the crop plant is grown in
an environment not
comprising plant diseases caused by fungal plant pathogens. Also of note is a
method for
increasing vigor of a crop plant wherein the crop plant is grown in an
environment comprising an
amount of moisture less than ideal for supporting growth of the crop plant.
Compounds and compositions of this invention can also be mixed with one or
more other
biologically active compounds or agents including fungicides, insecticides,
nematicides,
bactericides, acaricides, herbicides, herbicide safeners, growth regulators
such as insect molting
inhibitors and rooting stimulants, chemosterilants, semiochemicals,
repellents, attractants,
pheromones, feeding stimulants, plant nutrients, other biologically active
compounds or
entomopathogenic bacteria, virus or fungi to form a multi-component pesticide
giving an even
broader spectrum of agricultural protection. Thus the present invention also
pertains to a
composition comprising a compound of Formula 1 (in a fungicidally effective
amount) and at
least one additional biologically active compound or agent (in a biologically
effective amount)
and can further comprise at least one of a surfactant, a solid diluent or a
liquid diluent. The other
biologically active compounds or agents can be formulated in compositions
comprising at least
one of a surfactant, solid or liquid diluent. For mixtures of the present
invention, one or more
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
153
other biologically active compounds or agents can be formulated together with
a compound of
Formula 1, to form a premix, or one or more other biologically active
compounds or agents can
be formulated separately from the compound of Formula 1, and the formulations
combined
together before application (e.g., in a spray tank) or, alternatively, applied
in succession.
As mentioned in the Summary of the Invention, one aspect of the present
invention is a
fungicidal composition comprising (i.e. a mixture or combination of) a
compound of Formula 1,
an N-oxide, or a salt thereof (i.e. component (a)), and at least one other
fungicide (i.e. component
(b)). Of note is such a combination where the other fungicidal active
ingredient has different site
of action from the compound of Formula 1. In certain instances, a combination
with at least one
other fungicidal active ingredient having a similar spectrum of control but a
different site of action
will be particularly advantageous for resistance management. Thus, a
composition of the present
invention can further comprise a fungicidally effective amount of at least one
additional fungicidal
active ingredient having a similar spectrum of control but a different site of
action.
Examples of component (b) fungicides include acibenzolar-S-methyl, aldimorph,
ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl
(including benalaxyl-
M), benodanil, benomyl, benthiavalicarb (including benthiavalicarb-isopropyl),
benzovindiflupyr, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen,
blasticidin-S, boscalid,
bromuconazole, bupirimate, buthiobate, captafol, captan, carbendazim,
carboxin, carpropamid,
chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper hydroxide,
copper oxychloride,
copper sulfate, coumoxystrobin, cyazofamid, cyflufenamid, cymoxanil,
cyproconazole,
cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb,
difenoconazole,
diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole
(including
diniconazole-M), dinocap, dithianon, dithiolanes, dodemorph, dodine,
dipymetitrone, econazole,
edifenphos, enoxastrobin (also known as enestroburin), epoxiconazole,
etaconazole, ethaboxam,
ethirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenaminstrobin,
fenbuconazole,
fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph,
fenpyrazamine, fentin
acetate, fentin chloride, fentin hydroxide, ferbam, ferimzone, flometoquin,
florylpicoxamid,
fluazinam, fludioxonil, flufenoxystrobin, fluindapyr, flumorph, fluopicolide,
fluopimomide,
fluopyram, flouroimide, fluoxastrobin, fluquinconazole, flusilazole,
flusulfamide, flutianil,
flutolanil, flutriafol, fluxapyroxad, folpet, fthalide, fuberidazole,
furalaxyl, furametpyr, guazatine,
hexaconazole, hymexazole, imazalil, imibenconazole, iminoctadine albesilate,
iminoctadine
triacetate, iodocarb, ipconazole, ipfentrifluconazole, iprobenfos, iprodione,
iprovalicarb,
isoconazole, isofetamid, isoprothiolane, isoflucypram, isopyrazam, isotianil,
kasugamycin,
kresoxim-methyl, mancozeb, mandepropamid, mandestrobin, maneb, mepanipyrim,
mepronil,
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
154
meptyldinocap, metalaxyl (including metalaxyl-M/mefenoxam),
mefentrifluconazole,
metconazole, methasulfocarb, metiram, metominostrobin, metrafenone,
miconazole,
myclobutanil, naftifine, neo-asozin, nuarimol, octhilinone, ofurace,
orysastrobin, oxadixyl,
oxathiapiprolin, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline,
pefurazoate,
penconazole, pencycuron, penflufen, penthiopyrad, phosphorous acid (including
salts thereof,
e.g., fosetyl-aluminum), picarbutrazox, picoxystrobin, piperalin, polyoxin,
probenazole,
prochloraz, procymidone, propamacarb, propiconazole, propineb, proquinazid,
prothiocarb,
prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos,
pyribencarb,
pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyrisoxazole, pyroquilon,
pyrrolnitrin,
quinconazole, quinofumelin (Registry Number 861647-84-9) quinomethionate,
quinoxyfen,
quintozene, sedaxane, silthiofam, simeconazole, spiroxamine, streptomycin,
sulfur, tebuconazole,
tebufloquin, teclofthalam, tecnazene, terbinafine, tetraconazole,
thiabendazole, thifluzamide,
thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl,
tolnifanide, tolprocarb,
tolyfluanid, triadimefon, triadimenol, triarimol, triticonazole, triazoxide,
tribasic copper sulfate,
tricyclazole, triclopyricarb, tridemorph, trifloxystrobin, triflumizole,
triforine, trimorphamide,
uniconazole, uniconazole-P, validamycin, valifenalate (also known as
valiphenal), vinclozolin,
zineb, ziram, zoxamide, N-[2-(1S,2R)-[1,1'-bicyclopropyl] -2 -ylphenyl] -3 -
(difluoromethyl)- 1-
methy1-1H-pyrazole-4-carboxamide, a-(1-chlorocyclopropy1)- a- [2-(2,2-
dichlorocyclopropy1)-
ethyl] -1H-1,2,4-triazole-l-ethanol, (aS)- [3-(4-chloro-2-fluoropheny1)-5-(2,4-
difluoropheny1)-4-
isoxazolyl] -3 -pyridinemethanol, re1-1-1 [(2R,3 S)-3 -(2-chloropheny1)-2-
(2,4-difluoropheny1)-2 -
oxiranyl] methyl] - 1H-1,2,4-triazole, re/-2- [ [(2R,35)-3 -(2 -chloropheny1)-
2-(2,4-difluoropheny1)-
2-oxiranyl]methyl] -1,2-dihydro-3H-1,2,4-triazole-3-thione, re1-1-1 R2R,35)-3 -
(2 -chloropheny1)-
2-(2,4-difluoropheny1)-2-oxiranyl]methyl] -5-(2-propen-l-ylthio)-1H-1,2,4-
triazole, N- [2- [4- [ [3 -
(4-chloropheny1)-2-prop yn-l-yl]oxy] -3 -methoxyphenyl] ethyl] -3 -methyl-2-
[(methylsulfony1)-
amino]butanamide, N- [2- [4- [ [3 -(4-chloropheny1)-2-propyn-l-yl]oxy] -3 -
methoxyphenyl]ethyl] -
3 -methyl-2- [(ethylsulfonyl)amino]butanamide, N'- [4- [4-chloro-3 -
(trifluoromethyl)phenoxy] -2,5-
dimethylpheny1]-N-ethyl-N-methylmethanimidamide,
N-[[(cyclopropylmethoxy)amino][6-
(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, N-[2-(2,4-
dichloropheny1)-
2-methoxy-l-methylethyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-
carboxamide, N-(3',4'-
difluoro [1,1'-biphenyl] -2 -y1)-3 -(trifluoromethyl)-2 -pyrazinec arboxamide,
3 -(difluoromethyl)-N-
(2,3 -dihydro-1,1,3 -trimethy1-1H-inden-4-y1)-1-methy1-1H-pyrazole-4-
carboxamide, 5,8-di-
fluoro-N- [2- [3 -methoxy-4- [ [4-(trifluoromethyl)-2 -pyridinyl] oxy] phenyl]
ethyl] -4-quinazo -
linamine, 1-[4-[4- [5R- [(2,6-difluorophenoxy)methy1]-4,5-dihydro-3-
isoxazoly1]-2-thiazoly1]-1-
piperdinyl] -2- [5 -methyl-3 -(trifluoromethyl)-1H-pyrazol-1-yl] ethanone, 4-
fluorophenyl N-[1-
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
155
[[[1-(4-cyanophenyl)ethyl] sulfonyl]methyl]propyl]carbamate,
5-fluoro -2- [(4-fluoropheny1)-
methoxy]-4-pyrimidinamine, a-(methoxyimino)-N-methyl-2- [[ [1- [3-
(trifluoromethyl)phenyl]-
ethoxy] imino] methyl]benzeneacetamide, and [ [4-methoxy-2 - [ [R3S,7R,8R,9S)-
9-methyl- 8-(2-
methyl-l-oxopropoxy)-2,6-dioxo-7-(phenylmethyl)- 1,5 -dioxonan-3 -yl] amino]
carbonyl] -3-
pyridinyl]oxylmethyl 2-methylpropanoate. Therefore of note is a fungicidal
composition
comprising as component (a) a compound of Formula 1 (or an N-oxide or salt
thereof) and as
component (b) at least one fungicide selected from the preceding list.
Of particular note are combinations of compounds of Formula 1 (or an N-oxide
or salt
thereof) (i.e. Component (a) in compositions) with component (b) compounds
selected from
aminopyrifen (Registry Number 1531626-08-0), azoxystrobin, benzovindiflupyr,
bixafen, captan,
carpropamid, chlorothalonil, copper hydroxide, copper oxychloride, copper
sulfate, cymoxanil,
cyproconazole, cyprodinil, dichlobentiazox (Registry Number 957144-77-3),
diethofencarb,
difenoconazole, dimethomorph, dipymetitrone, epoxiconazole, ethaboxam,
fenarimol,
fenhexamid, fluazinam, fludioxonil, fluindapyr, fluopyram, flusilazole,
flutianil, flutriafol,
fluxapyroxad, folpet, ipflufenoquin (Registry Number 1314008-27-9), iprodione,
isofetamid,
isoflucypram, isopyrazam, kresoxim-methyl, mancozeb, mandestrobin,
meptyldinocap, metalaxyl
(including metalaxyl-M/mefenoxam), mefentrifluconazole, metconazole,
metrafenone,
metyltetraprole (Registry Number 1472649-01-6), myclobutanil, oxathiapiprolin,
penflufen,
penthiopyrad, phosphorous acid (including salts thereof, e.g., fosetyl-
aluminum), picoxystrobin,
propiconazole, proquinazid, prothioconazole, pyridachlometyl (Registry Number
1358061-55-8),
pyraclostrobin, pyrapropoyne (Registry Number 1803108-03-3), pyrimethanil,
sedaxane
spiroxamine, sulfur, tebuconazole, thiophanate-methyl, trifloxystrobin,
zoxamide, a-(1-
chlorocyclopropy1)-a- [2-(2,2-dichlorocyclopropyl)ethyl] -1H-1,2,4-triazole-l-
ethanol, N- [242,4-
dichloropheny1)-2-methoxy-l-methylethyl] -3 -(difluoromethyl)-1-methy1-1H-
pyrazole-4-
carboxamide, 3 -(difluoromethyl)-N-(2,3 -dihydro-1,1,3 -trimethy1-1H-inden-4-
y1)-1 -methyl-1H-
pyrazole-4-carboxamide,
14444- [5R-(2,6-difluoropheny1)-4,5 -dihydro-3 -isoxazolyl] -2-
thiazolyl] -1-piperidinyl] -2- [5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-
yl]ethanone, 1,1-di-
methylethyl
N-16- [[ [[(1-methy1-1H-tetrazol-5-y1)phenylmethylene] amino]oxy] methyl] -
2-
pyridinyl] c arb amate, 5-fluoro-2- [(4-fluorophenyl)methoxy]-4-
pyrimidinamine, ( aS)- [3 -(4-
chloro-2-fluoropheny1)-5-(2,4-difluoropheny1)-44 so xazolyl] -3 -
pyridinemethanol, re1-1-
[ R2R,3S)-3 -(2-chloropheny1)-2-(2,4-difluoropheny1)-2-oxiranyl]methyl] -1H-
1,2,4-triazole, re1-
2-11(2R,35)-3-(2-chloropheny1)-2-(2,4-difluorophenyl)-2-oxiranyl]methyl]-1,2-
dihydro-3H-
1,2,4-triazole-3-thione, and re1-1-11(2R,35)-3-(2-chloropheny1)-2-(2,4-
difluorophenyl)-2-oxiran-
yl]methyl]-5-(2-propen-1-ylthio)-1H-1,2,4-triazole (i.e. as Component (b) in
compositons).
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
156
Generally preferred for better control of plant diseases caused by fungal
plant pathogens
(e.g., lower use rate or broader spectrum of plant pathogens controlled) or
resistance management
are mixtures of a compound of Formula 1, an N-oxide, or salt thereof, with a
fungicidal compound
selected from the group: amisulbrom, azoxystrobin, benzovindiflupyr, bixafen,
boscalid,
carbendazim, carboxin, chlorothalonil, copper hydroxide, cymoxanil,
cyproconazole,
difenoconazole, dimethomorph, dimoxystrobin, epoxiconazole, fenpropidin,
fenpropimorph,
florylpicoxamid, fluazinam, fludioxonil, flufenoxystrobin, fluindapyr,
fluquinconazole,
fluopicolide, fluoxastrobin, flutriafol, fluxapyroxad, ipconazole,
ipfentrifluconazole, iprodione,
kresoxim-methyl, mancozeb, metalaxyl, mefenoxam, mefentrifluconazole,
metconazole,
metominostrobin, myclobutanil, paclobutrazole, penflufen, picoxystrobin,
prothioconazole,
pydiflumetofen, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyriofenone,
sedaxane,
silthiofam, tebuconazole, thiabendazole, thiophanate-methyl, thiram,
trifloxystrobin and
triticonazole.
In the fungicidal compositions of the present invention, component (a) (i.e.
at least one
compound selected from compounds of Formula 1, N-oxides, and salts thereof)
and component
(b) are present in fungicidally effective amounts. The weight ratio of
component (a) to component
(b) (i.e. one or more additional fungicidal compounds) is generally between
about 1:3000 to about
3000: 1, and more typically between about 1:500 and about 500:1. Of note are
compositions
where in the weight ratio of component (a) to component (b) is from about
125:1 to about 1:125.
With many fungicidal compounds of component (b), these compositions are
particularly effective
for controlling plant diseases caused by fungal plant pathogens. Of particular
note are
compositions wherein the weight ratio of component (a) to component (b) is
from about 25:1 to
about 1:25, or from about 5:1 to about 1:5. One skilled in the art can easily
determine through
simple experimentation the weight ratios and application rates of fungicidal
compounds necessary
for the desired spectrum of fungicidal protection and control. It will be
evident that including
additional fungicidal compounds in component (b) may expand the spectrum of
plant diseases
controlled beyond the spectrum controlled by component (a) alone. Furthermore,
Tables Al
through A21 and Cl through C21 exemplify weight ratios for combinations of
fungicidal
compounds of the present invention. Table B1 lists typical, more typical and
most typical ranges
of ratios involving particular fungicidal compounds of component (b).
Specific mixtures (compound numbers refer to compounds in Index Tables A
through L)
are listed in Tables Al through A21. In Table Al, each line below the column
headings
"Component (a)" and "Component (b)" specifically discloses a mixture of
Component (a), (i.e.
Compound 32), with a Component (b) fungicidal compound. The entries under the
heading
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
157
"Illustrative Ratios" disclose three specific weight ratios of Component (a)
to Component (b) for
the disclosed mixture. For example, the first line of Table Al discloses a
mixture of Compound
32 with acibenzolar-S-methyl and lists weight ratios of Compound 32 relative
to acibenzolar-S-
methyl of 1:1, 1:4 or 1:18.
Table Al
Component (a) Component (b)
Illustrative Ratios(*)
Compound 32 acibenzolar-S-methyl 1:1 1:4
1:18
Compound 32 aldimorph 7:1 3:1
1:1
Compound 32 ametoctradin 3:1 1:1
1:3
Compound 32 amisulbrom 1:1 1:2
1:6
Compound 32 anilazine 22:1
8:1 -- 4:1
Compound 32 azaconazole 2:1 1:2
1:4
Compound 32 azoxystrobin 3:1 1:1
1:3
Compound 32 benalaxyl 1:1 1:2
1:6
Compound 32 benalaxyl-M 1:1 1:3
1:8
Compound 32 benodanil 4:1 2:1
1:2
Compound 32 benomyl 11:1
4:1 -- 1:1
Compound 32 benthiavalicarb 1:1 1:4
1:12
Compound 3 benthiavalicarb-isopropyl 1:1 1:4
1:12
Compound 32 bethoxazin 15:1
5:1 2:1
Compound 32 binapacryl 15:1
5:1 -- 2:1
Compound 32 biphenyl 15:1
5:1 2:1
Compound 32 bitertanol 3:1 1:1
1:2
Compound 32 bixafen 2:1 1:1
1:3
Compound 32 blasticidin-S 1:4 1:12
1:30
Compound 32 Bordeaux mixture (tribasic copper sulfate) 45:1
15:1 5:1
Compound 32 boscalid 4:1 2:1
1:2
Compound 32 bromuconazole 3:1 1:1
1:3
Compound 32 bupirimate 1:3 1:10
1:30
Compound 32 captafol 15:1
5:1 2:1
Compound 32 captan 15:1
5:1 -- 2:1
Compound 32 carbendazim 11:1
4:1 -- 2:1
Compound 32 carboxin 4:1 2:1
1:2
Compound 32 carpropamid 3:1 1:1
1:3
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
158
Component (a) Component (b)
Illustrative Ratios(*)
Compound 32 chloroneb 100:1 35:1 14:1
Compound 32 chlorothalonil 15:1 5:1 2:1
Compound 32 chlozolinate 11:1 4:1 2:1
Compound 32 clotrimazole 3:1 1:1 1:3
Compound 32 copper hydroxide 45:1 15:1 5:1
Compound 32 copper oxychloride 45:1 15:1 5:1
Compound 32 cyazofamid 1:1 1:2 1:6
Compound 32 cyflufenamid 1:2 1:6 1:24
Compound 32 cymoxanil 1:1 1:2 1:5
Compound 32 cyproconazole 1:1 1:2 1:6
Compound 32 cyprodinil 4:1 2:1 1:2
Compound 32 dichlofluanid 15:1 5:1 2:1
Compound 32 diclocymet 15:1 5:1 2:1
Compound 32 diclomezine 3:1 1:1 1:3
Compound 32 dicloran 15:1 5:1 2:1
Compound 32 diethofencarb 7:1 2:1 1:2
Compound 32 difenoconazole 1:1 1:3 1:12
Compound 32 diflumetorim 15:1 5:1 2:1
Compound 32 dimethirimol 1:3 1:8 1:30
Compound 32 dimethomorph 3:1 1:1 1:2
Compound 32 dimoxystrobin 2:1 1:1 1:4
Compound 32 diniconazole 1:1 1:3 1:8
Compound 32 diniconazole-M 1:1 1:3 1:12
Compound 32 dinocap 2:1 1:1 1:3
Compound 32 dithianon 5:1 2:1 1:2
Compound 32 dodemorph 7:1 3:1 1:1
Compound 32 dodine 10:1 4:1 2:1
Compound 32 edifenphos 3:1 1:1 1:3
Compound 32 enestroburin 2:1 1:1 1:4
Compound 32 epoxiconazole 1:1 1:3 1:7
Compound 32 etaconazole 1:1 1:3 1:7
Compound 32 ethaboxam 2:1 1:1 1:3
Compound 32 ethirimol 7:1 3:1 1:1
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
159
Component (a) Component (b)
Illustrative Ratios(*)
Compound 32 etridiazole 7:1 2:1 1:2
Compound 32 famoxadone 2:1 1:1 1:4
Compound 32 fenamidone 2:1 1:1 1:4
Compound 32 fenaminstrobin 3:1 1:1 1:3
Compound 32 fenarimol 1:2 1:7 1:24
Compound 32 fenbuconazole 1:1 1:3 1:10
Compound 32 fenfuram 4:1 1:1 1:2
Compound 32 fenhexamid 10:1 4:1 2:1
Compound 32 fenoxanil 15:1 4:1 1:1
Compound 32 fenpiclonil 15:1 5:1 2:1
Compound 32 fenpropidin 7:1 2:1 1:1
Compound 32 fenpropimorph 7:1 2:1 1:1
Compound 32 fenpyrazamine 3:1 1:1 1:3
Compound 32 fentin salt such as fentin acetate, fentin chloride or fentin
3:1 1:1 1:3
hydroxide
Compound 32 ferbam 30:1 10:1 4:1
Compound 32 ferimzone 7:1 2:1 1:2
Compound 32 fluazinam 3:1 1:1 1:2
Compound 32 fludioxonil 2:1 1:1 1:4
Compound 32 flumetover 3:1 1:1 1:2
Compound 32 flumorph 3:1 1:1 1:3
Compound 32 fluopicolide 1:1 1:2 1:6
Compound 32 fluopyram 3:1 1:1 1:3
Compound 32 fluoroimide 37:1 14:1 5:1
Compound 32 fluoxastrobin 1:1 1:2 1:6
Compound 32 fluquinconazole 1:1 1:2 1:4
Compound 32 flusilazole 3:1 1:1 1:3
Compound 32 flusulfamide 15:1 5:1 2:1
Compound 32 flutianil 1:1 1:2 1:6
Compound 32 flutolanil 4:1 1:1 1:2
Compound 32 flutriafol 1:1 1:2 1:4
Compound 32 fluxapyroxad 2:1 1:1 1:3
Compound 32 folpet 15:1 5:1 2:1
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
160
Component (a) Component (b)
Illustrative Ratios(*)
Compound 32 fosetyl-aluminum 30:1 12:1 5:1
Compound 32 fuberidazole 11:1 4:1 2:1
Compound 32 furalaxyl 1:1 1:2 1:6
Compound 32 furametpyr 15:1 5:1 2:1
Compound 32 guazatine 15:1 5:1 2:1
Compound 32 hexaconazole 1:1 1:2 1:5
Compound 32 hymexazol 75:1 25:1 9:1
Compound 32 imazalil 1:1 1:2 1:5
Compound 32 imibenconazole 1:1 1:2 1:5
Compound 32 iminoctadine 15:1 4:1 1:1
Compound 32 iodocarb 15:1 5:1 2:1
Compound 32 ipconazole 1:1 1:2 1:5
Compound 32 iprobenfos 15:1 5:1 2:1
Compound 32 iprodione 15:1 5:1 2:1
Compound 32 iprovalicarb 2:1 1:1 1:3
Compound 32 isoprothiolane 45:1 15:1 5:1
Compound 32 isopyrazam 2:1 1:1 1:3
Compound 32 isotianil 2:1 1:1 1:3
Compound 32 kasugamycin 1:2 1:7 1:24
Compound 32 kresoxim-methyl 2:1 1:1 1:4
Compound 32 mancozeb 22:1 7:1 3:1
Compound 32 mandipropamid 2:1 1:1 1:4
Compound 32 maneb 22:1 7:1 3:1
Compound 32 mepanipyrim 6:1 2:1 1:1
Compound 32 mepronil 1:1 1:2 1:6
Compound 32 meptyldinocap 2:1 1:1 1:3
Compound 32 metalaxyl 1:1 1:2 1:6
Compound 32 metalaxyl-M 1:1 1:4 1:12
Compound 32 metconazole 1:1 1:2 1:6
Compound 32 methasulfocarb 15:1 5:1 2:1
Compound 32 metiram 15:1 5:1 2:1
Compound 32 metominostrobin 3:1 1:1 1:3
Compound 32 metrafenone 2:1 1:1 1:4
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
161
Component (a) Component (b)
Illustrative Ratios(*)
Compound 32 myclobutanil 1:1 1:3 1:8
Compound 32 naftifine 15:1 5:1
2:1
Compound 32 neo-asozin (ferric methanearsonate) 15:1 5:1
2:1
Compound 32 nuarimol 3:1 1:1 1:3
Compound 32 octhilinone 15:1 4:1
1:1
Compound 32 ofurace 1:1 1:2 1:6
Compound 32 orysastrobin 3:1 1:1 1:3
Compound 32 oxadixyl 1:1 1:2 1:6
Compound 32 oxolinic acid 7:1 2:1 1:2
Compound 32 oxpoconazole 1:1 1:2 1:5
Compound 32 oxycarboxin 4:1 1:1 1:2
Compound 32 oxytetracycline 3:1 1:1 1:3
Compound 32 pefurazoate 15:1 5:1
2:1
Compound 32 penconazole 1:2 1:6 1:15
Compound 32 pencycuron 11:1 4:1
2:1
Compound 32 penflufen 2:1 1:1 1:3
Compound 32 penthiopyrad 2:1 1:1 1:3
Compound 32 phosphorous acid or a salt thereof 15:1 6:1
2:1
Compound 32 phthalide 15:1 6:1
2:1
Compound 32 picoxystrobin 1:1 1:2 1:5
Compound 32 piperalin 3:1 1:1 1:3
Compound 32 polyoxin 3:1 1:1 1:3
Compound 32 probenazole 3:1 1:1 1:3
Compound 32 prochloraz 7:1 2:1 1:2
Compound 32 procymidone 11:1 4:1
2:1
Compound 32 propamocarb or propamocarb-hydrochloride 10:1 4:1
2:1
Compound 32 propiconazole 1:1 1:2 1:5
Compound 32 propineb 11:1 4:1
2:1
Compound 32 proquinazid 1:1 1:3 1:12
Compound 32 prothiocarb 3:1 1:1 1:3
Compound 32 prothioconazole 1:1 1:2 1:5
Compound 32 pyraclostrobin 2:1 1:1 1:4
Compound 32 pyrametostrobin 2:1 1:1 1:4
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
162
Component (a) Component (b)
Illustrative Ratios(*)
Compound 32 pyraoxystrobin 2:1 1:1 1:4
Compound 32 pyrazophos 15:1 4:1 1:1
Compound 32 pyribencarb 4:1 1:1 1:2
Compound 32 pyributicarb 15:1 4:1 1:1
Compound 32 pyrifenox 3:1 1:1 1:3
Compound 32 pyrimethanil 3:1 1:1 1:2
Compound 32 pyriofenone 2:1 1:1 1:4
Compound 32 pyrisoxazole 3:1 1:1 1:3
Compound 32 pyroquilon 3:1 1:1 1:3
Compound 32 pynolnitrin 15:1 5:1 2:1
Compound 32 quinconazole 1:1 1:2 1:4
Compound 32 quinomethionate 15:1 5:1 2:1
Compound 32 quinoxyfen 1:1 1:2 1:6
Compound 32 quintozene 15:1 5:1 2:1
Compound 32 silthiofam 2:1 1:1 1:4
Compound 32 simeconazole 1:1 1:2 1:5
Compound 32 spiroxamine 5:1 2:1 1:2
Compound 32 streptomycin 3:1 1:1 1:3
Compound 32 sulfur 75:1 25:1 9:1
Compound 32 tebuconazole 1:1 1:2 1:5
Compound 32 tebufloquin 3:1 1:1 1:3
Compound 32 tecloftalam 15:1 5:1 2:1
Compound 32 tecnazene 15:1 5:1 2:1
Compound 32 terbinafine 15:1 5:1 2:1
Compound 32 tetraconazole 1:1 1:2 1:5
Compound 32 thiabendazole 11:1 4:1 2:1
Compound 32 thifluzamide 3:1 1:1 1:3
Compound 32 thiophanate 11:1 4:1 2:1
Compound 32 thiophanate-methyl 11:1 4:1 2:1
Compound 32 thiram 37:1 14:1 5:1
Compound 32 tiadinil 2:1 1:1 1:3
Compound 32 tolclofos-methyl 37:1 14:1 5:1
Compound 32 tolnifanide 3:1 1:1 1:3
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
163
Component (a) Component (b)
Illustrative Ratios(*)
Compound 32 tolylfluanid 15:1 5:1 2:1
Compound 32 triadimefon 1:1 1:2 1:5
Compound 32 triadimenol 1:1 1:2 1:5
Compound 32 triarimol 1:2 1:7 1:24
Compound 32 triazoxide 15:1 5:1 2:1
Compound 32 tricyclazole 3:1 1:1 1:3
Compound 32 tridemorph 7:1 2:1 1:1
Compound 32 trifloxystrobin 2:1 1:1 1:4
Compound 32 triflumizole 3:1 1:1 1:3
Compound 32 triforine 3:1 1:1 1:3
Compound 32 trimorphamide 7:1 2:1 1:2
Compound 32 triticonazole 1:1 1:2 1:5
Compound 32 uniconazole 1:1 1:2 1:5
Compound 32 validamycin 3:1 1:1 1:3
Compound 32 valifenalate 2:1 1:1 1:4
Compound 32 vinclozolin 15:1 6:1 2:1
Compound 32 zineb 37:1 14:1 5:1
Compound 32 ziram 37:1 14:1 5:1
Compound 32 zoxamide 2:1 1:1 1:4
Compound 32 5-chloro-6-(2,4,6-trifluoropheny0-7-(4-methylpiperidin- 1:1
1:2 1:6
1-y1) [1,2,4] triazolo [1,5-a]pyrimidine (DPX-BAS600F)
Compound 32 N-[2- [4-[ [3-(4-chioropheny1)-2-propyn- 1 -yl] oxy] -3-methoxy-
2:1 1:1 1:4
phenyl] ethyl] -3-methyl-2- [(methylsulfonyeamino]-
butanamide
Compound 32 N- [2- [4-[ [3-(4-chioropheny1)-2-propyn- 1 -yl] oxy] -3-
methoxy- 2:1 1:1 1:4
phenyl] ethyl] -3-methyl-2- [(ethylsulfonypamino]butanamide
Compound 32 4-fluorophenyl N-[1-[[[1-(4-cyanophenyeethyl] sulfonyl] -
2:1 1:1 1:4
methyl]propyl]carbamate
Compound 32 N-[ [(cyclopropylmethoxy)amino][6-(difluoromethoxy)- 1:2
1:7 1:24
2,3 -difluorophenyl] methylene]benzeneacetamide
Compound 32 a-[methoxyimino]-N-methy1-2-[[[1-[3-(trifluoromethyl)- 3:1
1:1 1:3
phenyl] ethoxy] imino] methyl]benzeneacetamide
Compound 32 N'- [4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethyl-
3:1 1:1 1:3
phenyl]-N-ethyl-N-methylmethanimidamide
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
164
(*) Ratios of Component (a) relative to Component (b) by weight.
Tables A2 through A21 are each constructed the same as Table Al above except
that entries
below the "Component (a)" column heading are replaced with the respective
Component (a)
Column Entry shown below. Thus, for example, in Table A2 the entries below the
"Component
(a)" column heading all recite "Compound 64", and the first line below the
column headings in
Table A2 specifically discloses a mixture of Compound 64 with acibenzolar-S-
methyl. Tables A3
through A21 are constructed similarly.
Table Number Component (a) Column Entry
Table Number Component (a) Column Entry
A2 Compound 64 Al2 Compound 221
A3 Compound 71 A13 Compound 229
A4 Compound 126 A14 Compound 231
A5 Compound 127 A15 Compound 262
A6 Compound 132 A16 Compound 263
A7 Compound 162 A17 Compound 265
A8 Compound 163 A18 Compound 297
A9 Compound 171 A19 Compound 330
A10 Compound 186 A20 Compound 331
All Compound 218 A21 Compound 364
Table B1 lists specific combinations of a Component (b) compound with
Component (a)
illustrative of the mixtures, compositions and methods of the present
invention. The first column
of Table B1 lists the specific Component (b) compound (e.g., "acibenzolar-S-
methyl" in the first
line). The second, third and fourth columns of Table B1 lists ranges of weight
ratios for rates at
which the Component (a) compound is typically applied to a field-grown crop
relative to
Component (b). Thus, for example, the first line of Table B1 discloses the
combination of a
compound of Component (a) with acibenzolar-S-methyl is typically applied in a
weight ratio of
the Component (a) to Component (b) of between 2:1 to 1:180. The remaining
lines of Table B1
are to be construed similarly. Of particular note is a composition comprising
a mixture of any one
of the compounds listed in Embodiment 238 as Component (a) with a compound
listed in the
Component (b) column of Table B1 according to the weight ratios disclosed in
Table Bl. Table
B1 thus supplements the specific ratios disclosed in Tables Al through A21
with ranges of ratios
for these combinations.
Table Bl
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
165
Typical Typical Most
Typical
Component (b) Weight Ratio Weight Ratio Weight
Ratio
acibenzolar-S-methyl 2:1 to 1:180 1:1 to 1:60 1:1 to
1:18
aldimorph 30:1 to 1:3 10:1 to 1:1 7:1 to
1:1
ametoctradin 9:1 to 1:18 3:1 to 1:6 3:1 to
1:3
amisulbrom 6:1 to 1:18 2:1 to 1:6 1:1 to
1:6
anilazine 90:1 to 2:1 30:1 to 4:1 22:1 to
4:1
azaconazole 7:1 to 1:18 2:1 to 1:6 2:1 to
1:4
azoxystrobin 9:1 to 1:12 3:1 to 1:4 3:1 to
1:3
benalaxyl 4:1 to 1:18 1:1 to 1:6 1:1 to
1:6
benalaxyl-M 4:1 to 1:36 1:1 to 1:12 1:1 to
1:8
benodanil 18:1 to 1:6 6:1 to 1:2 4:1 to
1:2
benomyl 45:1 to 1:4 15:1 to 1:1 11:1 to
1:1
benthiavalicarb or benthiavalicarb-isopropyl 2:1 to 1:36 1:1 to
1:12 1:1 to 1:12
bethoxazin 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
binapacryl 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
biphenyl 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
bitertanol 15:1 to 1:5 5:1 to 1:2 3:1 to
1:2
bixafen 12:1 to 1:9 4:1 to 1:3 2:1 to
1:3
blasticidin-S 3:1 to 1:90 1:1 to 1:30 1:4 to
1:30
boscalid 18:1 to 1:6 6:1 to 1:2 4:1 to
1:2
bromuconazole 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
bupirimate 3:1 to 1:90 1:1 to 1:30 1:3 to
1:30
captafol 90:1 to 1:4 30:1 to 1:2 15:1 to
2:1
captan 90:1 to 1:4 30:1 to 1:2 15:1 to
2:1
carbendazim 45:1 to 1:4 15:1 to 1:2 11:1 to
2:1
carboxin 18:1 to 1:6 6:1 to 1:2 4:1 to
1:2
carpropamid 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
chloroneb 300:1 to 2:1 100:1 to 4:1 100:1 to 14:1
chlorothalonil 90:1 to 1:4 30:1 to 1:2 15:1 to
2:1
chlozolinate 45:1 to 1:2 15:1 to 2:1 11:1 to
2:1
clotrimazole 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
copper salts such as Bordeaux mixture
450:1 to 1:1 150:1 to 4:1 45:1 to
5:1
(tribasic copper sulfate), copper
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
166
Typical Typical Most Typical
Component (b) Weight Ratio Weight Ratio Weight
Ratio
oxychloride, copper sulfate and copper
hydroxide
cyazofamid 4:1 to 1:18 1:1 to 1:6 1:1 to 1:6
cyflufenamid 1:1 to 1:90 1:2 to 1:30 1:2 to
1:24
cymoxanil 6:1 to 1:18 2:1 to 1:6 1:1 to 1:5
cyproconazole 4:1 to 1:18 1:1 to
1:6 1:1 to 1:6
cyprodinil 22:1 to 1:9 7:1 to 1:3 4:1 to 1:2
dichlofluanid 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1
diclocymet 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1
diclomezine 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3
dicloran 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1
diethofencarb 22:1 to 1:9 7:1 to 1:3 7:1 to 1:2
difenoconazole 4:1 to 1:36 1:1 to
1:12 1:1 to 1:12
diflumetorim 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1
dimethirimol 3:1 to 1:90 1:1 to 1:30 1:3 to
1:30
dimethomorph 9:1 to 1:6 3:1 to
1:2 3:1 to 1:2
dimoxystrobin 9:1 to 1:18 3:1 to
1:6 2:1 to 1:4
diniconazole 3:1 to 1:36 1:1 to 1:12 1:1 to 1:8
diniconazole M 3:1 to 1:90 1:1 to
1:30 1:1 to 1:12
dinocap 7:1 to 1:9 2:1 to 1:3 2:1 to 1:3
dithianon 15:1 to 1:4 5:1 to 1:2 5:1 to 1:2
dodemorph 30:1 to 1:3 10:1 to 1:1 7:1 to 1:1
dodine 30:1 to 1:2 10:1 to 2:1 10:1 to
2:1
edifenphos 30:1 to 1:9 10:1 to
1:3 3:1 to 1:3
enestroburin 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4
epoxiconazole 3:1 to 1:36 1:1 to
1:12 1:1 to 1:7
etaconazole 3:1 to 1:36 1:1 to 1:12 1:1 to 1:7
ethaboxam 7:1 to 1:9 2:1 to 1:3 2:1 to 1:3
ethirimol 30:1 to 1:3 10:1 to 1:1 7:1 to
1:1
etridiazole 30:1 to 1:9 10:1 to 1:3 7:1 to
1:2
famoxadone 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4
fenamidone 6:1 to 1:18 2:1 to 1:6 2:1 to 1:4
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
167
Typical Typical Most
Typical
Component (b) Weight Ratio Weight Ratio Weight Ratio
fenaminstrobin 9:1 to 1:18 3:1 to 1:6 3:1 to 1:3
fenarimol 3:1 to 1:90 1:1 to 1:30 1:2 to
1:24
fenbuconazole 3:1 to 1:30 1:1 to 1:10 1:1 to 1:10
fenfuram 18:1 to 1:6 6:1 to 1:2 4:1 to
1:2
fenhexamid 30:1 to 1:2 10:1 to 2:1 10:1 to
2:1
fenoxanil 150:1 to 1:36 50:1 to 1:12 15:1 to
1:1
fenpiclonil 75:1 to 1:9 25:1 to 1:3 15:1 to
2:1
fenpropidin 30:1 to 1:3 10:1 to 1:1 7:1 to
1:1
fenpropimorph 30:1 to 1:3 10:1 to 1:1 7:1 to 1:1
fenpyrazamine 100:1 to 1:100 10:1 to 1:10 3:1 to 1:3
fentin salt such as the acetate, chloride or
15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
hydroxide
ferbam 300:1 to 1:2 100:1 to 2:1 30:1 to
4:1
ferimzone 30:1 to 1:5 10:1 to 1:2 7:1 to
1:2
fluazinam 22:1 to 1:5 7:1 to 1:2 3:1 to
1:2
fludioxonil 7:1 to 1:12 2:1 to 1:4 2:1 to
1:4
flumetover 9:1 to 1:6 3:1 to 1:2 3:1 to
1:2
flumorph 9:1 to 1:18 3:1 to 1:6 3:1 to
1:3
fluopicolide 3:1 to 1:18 1:1 to 1:6 1:1 to
1:6
fluopyram 15:1 to 1:90 5:1 to 1:30 3:1 to
1:3
fluoromide 150:1 to 2:1 50:1 to 4:1 37:1 to
5:1
fluoxastrobin 4:1 to 1:18 1:1 to 1:6 1:1 to 1:6
fluquinconazole 4:1 to 1:12 1:1 to 1:4 1:1 to 1:4
flusilazole 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
flusulfamide 90:1 to 1:2 30:1 to 2:1 15:1 to
2:1
flutianil 7:1 to 1:36 2:1 to 1:12 1:1 to
1:6
flutolanil 18:1 to 1:6 6:1 to 1:2 4:1 to
1:2
flutriafol 4:1 to 1:12 1:1 to 1:4 1:1 to
1:4
fluxapyroxad 12:1 to 1:9 4:1 to 1:3 2:1 to 1:3
folpet 90:1 to 1:4 30:1 to 1:2 15:1 to
2:1
fosetyl-aluminum 225:1 to 2:1 75:1 to 5:1 30:1 to
5:1
fuberidazole 45:1 to 1:4 15:1 to 1:2 11:1 to
2:1
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
168
Typical Typical Most
Typical
Component (b) Weight Ratio Weight Ratio Weight
Ratio
furalaxyl 15:1 to 1:45 5:1 to 1:15 1:1 to
1:6
furametpyr 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1
guazatine or iminoctadine 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
hexaconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5
hymexazol 225:1 to 2:1 75:1 to 4:1 75:1 to 9:1
imazalil 7:1 to 1:18 2:1 to 1:6 1:1 to
1:5
imibenconazole 15:1 to 1:36 5:1 to 1:12 -- 1:1 to 1:5
iodocarb 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
ipconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5
iprobenfos 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
iprodione 120:1 to 1:2 40:1 to 2:1 15:1 to
2:1
iprovalicarb 9:1 to 1:9 3:1 to 1:3 2:1 to 1:3
isoprothiolane 150:1 to 2:1 50:1 to 4:1 45:1 to 5:1
isopyrazam 12:1 to 1:9 4:1 to 1:3 2:1 to 1:3
isotianil 12:1 to 1:9 4:1 to 1:3 2:1 to
1:3
kasugamycin 7:1 to 1:90 2:1 to 1:30 1:2 to
1:24
kresoxim-methyl 7:1 to 1:18 2:1 to 1:6 2:1 to
1:4
mancozeb 180:1 to 1:3 60:1 to 2:1 22:1 to
3:1
mandipropamid 6:1 to 1:18 2:1 to 1:6 2:1 to 1:4
maneb 180:1 to 1:3 60:1 to 2:1 22:1 to
3:1
mepanipyrim 18:1 to 1:3 6:1 to 1:1 6:1 to 1:1
mepronil 7:1 to 1:36 2:1 to 1:12 1:1 to
1:6
meptyldinocap 7:1 to 1:9 2:1 to 1:3 2:1 to 1:3
metalaxyl 15:1 to 1:45 5:1 to 1:15 1:1 to
1:6
metalaxyl-M 7:1 to 1:90 2:1 to 1:30 1:1 to 1:12
metconazole 3:1 to 1:18 1:1 to 1:6 1:1 to 1:6
methasulfocarb 150:1 to 1:36 50:1 to 1:12 15:1 to 1:1
metiram 150:1 to 1:36 50:1 to 1:12 15:1 to
1:1
metominostrobin 9:1 to 1:12 3:1 to 1:4 3:1 to
1:3
metrafenone 6:1 to 1:12 2:1 to 1:4 2:1 to 1:4
myclobutanil 5:1 to 1:26 1:1 to 1:9 1:1 to
1:8
naftifine 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
169
Typical Typical Most
Typical
Component (b) Weight Ratio Weight Ratio Weight Ratio
neo-asozin (ferric methanearsonate) 150:1 to 1:36 50:1 to
1:12 15:1 to 2:1
nuarimol 15:1 to 1:9 5:1 to 1:3 -- 3:1 to 1:3
octhilinone 150:1 to 1:36 50:1 to 1:12 15:1 to 1:1
ofurace 15:1 to 1:45 5:1 to 1:15 1:1 to 1:6
orysastrobin 9:1 to 1:12 3:1 to 1:4 3:1 to 1:3
oxadixyl 15:1 to 1:45 5:1 to 1:15 1:1 to 1:6
oxolinic acid 30:1 to 1:9 10:1 to 1:3 7:1 to 1:2
oxpoconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5
oxycarboxin 18:1 to 1:6 6:1 to 1:2 -- 4:1 to 1:2
oxytetracycline 15:1 to 1:9 5:1 to 1:3 -- 3:1 to 1:3
pefurazoate 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1
penconazole 1:1 to 1:45 1:2 to 1:15 1:2 to
1:15
pencycuron 150:1 to 1:2 50:1 to 2:1 11:1 to 2:1
penflufen 12:1 to 1:9 4:1 to 1:3 2:1 to 1:3
penthiopyrad 12:1 to 1:9 4:1 to 1:3 -- 2:1 to 1:3
phosphorous acid and salts thereof 150:1 to 1:36 50:1 to
1:12 15:1 to 2:1
phthalide 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1
picoxystrobin 7:1 to 1:18 2:1 to
1:6 1:1 to 1:5
piperalin 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3
polyoxin 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3
probenazole 15:1 to 1:9 5:1 to 1:3 3:1 to 1:3
prochloraz 22:1 to 1:4 7:1 to 1:1 7:1 to 1:2
procymidone 45:1 to 1:3 15:1 to 1:1 11:1 to
2:1
propamocarb or propamocarb-
30:1 to 1:2 10:1 to 2:1 10:1 to 2:1
hydrochloride
propiconazole 4:1 to 1:18 1:1 to 1:6 1:1 to 1:5
propineb 45:1 to 1:2 15:1 to 2:1 11:1 to
2:1
proquinazid 3:1 to 1:36 1:1 to 1:12 -- 1:1 to
1:12
prothiocarb 9:1 to 1:18 3:1 to 1:6 3:1 to 1:3
prothioconazole 6:1 to 1:18 2:1 to 1:6 -- 1:1 to 1:5
pyraclostrobin 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4
pyrametostrobin 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
170
Typical Typical Most
Typical
Component (b) Weight Ratio Weight Ratio Weight
Ratio
pyraoxystrobin 9:1 to 1:18 3:1 to 1:6 2:1 to 1:4
pyrazophos 150:1 to 1:36 50:1 to 1:12 15:1 to
1:1
pyribencarb 15:1 to 1:6 5:1 to 1:2 4:1 to
1:2
pyrifenox 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
pyrimethanil 30:1 to 1:6 10:1 to 1:2 3:1 to
1:2
pyriofenone 6:1 to 1:12 2:1 to 1:4 2:1 to
1:4
pyrisoxazole 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
pyroquilon 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
pyrrolnitrin 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
quinconazole 4:1 to 1:12 1:1 to 1:4 1:1 to
1:4
quinmethionate 150:1 to 1:36 50:1 to 1:12 15:1 to 2:1
quinoxyfen 4:1 to 1:18 1:1 to 1:6 1:1 to
1:6
quintozene 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
silthiofam 7:1 to 1:18 2:1 to 1:6 2:1 to
1:4
simeconazole 15:1 to 1:36 5:1 to 1:12 1:1 to 1:5
spiroxamine 22:1 to 1:4 7:1 to 1:2 5:1 to
1:2
streptomycin 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
sulfur 300:1 to 3:1 100:1 to 9:1 75:1 to
9:1
tebuconazole 7:1 to 1:18 2:1 to 1:6 1:1 to
1:5
tebufloquin 100:1 to 1:100 10:1 to 1:10 3:1 to
1:3
tecloftalam 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
tecnazene 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
terbinafine 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
tetraconazole 15:1 to 1:36 5:1 to 1:12 1:1 to
1:5
thiabendazole 45:1 to 1:4 15:1 to 1:2 11:1 to 2:1
thifluzamide 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
thiophanate 45:1 to 1:3 15:1 to 2:1 11:1 to
2:1
thiophanate-methyl 45:1 to 1:3 15:1 to 2:1 11:1 to
2:1
thiram 150:1 to 1:2 50:1 to 2:1 37:1 to
5:1
tiadinil 12:1 to 1:9 4:1 to 1:3 2:1 to
1:3
tolclofos-methyl 150:1 to 1:2 50:1 to 2:1 37:1 to 5:1
tolnifanide 15:1 to 1:18 5:1 to 1:6 3:1 to
1:3
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
171
Typical Typical Most
Typical
Component (b) Weight Ratio Weight Ratio Weight
Ratio
tolylfluanid 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
triadimefon 15:1 to 1:36 5:1 to 1:12 1:1 to
1:5
triadimenol 15:1 to 1:36 5:1 to 1:12 1:1 to
1:5
triarimol 3:1 to 1:90 1:1 to 1:30 1:2 to
1:24
triazoxide 150:1 to 1:36 50:1 to 1:12 15:1 to
2:1
tricyclazole 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
tridemorph 30:1 to 1:3 10:1 to 1:1 7:1 to
1:1
trifloxystrobin 6:1 to 1:18 2:1 to 1:6 2:1 to
1:4
triflumizole 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
triforine 15:1 to 1:9 5:1 to 1:3 3:1 to
1:3
trimorphamide 45:1 to 1:9 15:1 to 1:3 7:1 to
1:2
triticonazole 15:1 to 1:36 5:1 to 1:12 1:1 to
1:5
uniconazole 15:1 to 1:36 5:1 to 1:12 1:1 to
1:5
validamycin 150:1 to 1:36 50:1 to 1:12 3:1 to
1:3
valifenalate 6:1 to 1:18 2:1 to 1:6 2:1 to
1:4
vinclozolin 120:1 to 1:2 40:1 to 2:1 15:1 to
2:1
zineb 150:1 to 1:2 50:1 to 2:1 37:1 to
5:1
ziram 150:1 to 1:2 50:1 to 2:1 37:1 to
5:1
zoxamide 6:1 to 1:18 2:1 to 1:6 2:1 to
1:4
5-chloro-6-(2,4,6-trifluorophenye-
7-(4-methylpiperidin-l-y1)[1,2,4]triazolo- 15:1 to 1:36 5:1 to
1:12 1:1 to 1:6
[1,5-a]pyrimidine (DPX-BAS600F)
N- [2-[4-[[3-(4-chloropheny1)-2-propyn-
1-yl]oxy]-3-methoxyphenyl]ethy1]-
6:1 to 1:18 2:1 to 1:6 2:1 to
1:4
3-methy1-2-[(methylsulfonyl)amino]-
butanamide
N- [2-[44[3-(4-chloropheny1)-2-propyn-1-
yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl- 6:1 to 1:18 2:1 to
1:6 2:1 to 1:4
2-[(ethylsulfonyl)amino]butanamide
4-fluorophenyl N-[1-[[[1-(4-cyanopheny1)-
6:1 to 1:18 2:1 to 1:6 2:1 to
1:4
ethyl]sulfonyl]methyl]propyl]carbamate
N-[ [(cyclopropylmethoxy)amino][6- 1:1 to 1:90 1:2 to
1:30 1:2 to 1:24
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
172
Typical Typical
Most Typical
Component (b) Weight Ratio Weight Ratio
Weight Ratio
(difluoromethoxy)-2,3-difluorophenyfl-
methylene]benzeneacetamide
a-[methoxyimino]-N-methyl-2-[[[1-[3-
(trifluoromethypphenyflethoxy]imino]- 9:1 to 1:18 3:1 to 1:6 3:1 to
1:3
methyflbenzeneacetamide
N'- [4-[4-chloro-3-(trifluoromethyl)-
phenoxy]-2,5-dimethylphenyl]-N-ethyl- 15:1 to 1:18 5:1 to 1:6 3:1 to
1:3
N-methylmethanimidamide
As already noted, the present invention includes embodiments wherein in the
composition
comprising components (a) and (b), component (b) comprises at least one
fungicidal compound
from each of two groups selected from (b 1) through (b54). Tables Cl through
C21 list specific
mixtures (compound numbers refer to compounds in Index Tables A through L) to
illustrate
embodiments wherein component (b) includes at least one fungicidal compound
from each of two
groups selected from (b 1) through (b54). In Table Cl, each line below the
column headings
"Component (a)" and "Component (b)" specifically discloses a mixture of
Component (a), which
is Compound 32, with at least two Component (b) fungicidal compounds. The
entries under the
heading "Illustrative Ratios" disclose three specific weight ratios of
Component (a) to each
Component (b) fungicidal compound in sequence for the disclosed mixture. For
example, the first
line discloses a mixture of Compound 32 with cyproconazole and azoxystrobin
and lists weight
ratios of Compound 32 to cyproconazole to azoxystrobin of 1:1:1 , 2:1:1 or
3:1:1.
Table Cl
Component (a) Component (b) Illustrative
Ratios(*)
Compound 32 cyproconazole azoxystrobin 1:1:1 2:1:1
3:1:1
Compound 32 cyproconazole kresoxim-methyl 1:1:1 2:1:1
3:1:1
Compound 32 cyproconazole picoxystrobin 1:1:1 2:1:1
3:1:1
Compound 32 cyproconazole pyraclostrobin 1:1:1 2:1:1
3:1:1
Compound 32 cyproconazole pyrametrostrobin 1:1:1 2:1:1
3:1:1
Compound 32 cyproconazole pyraoxystrobin 1:1:1 2:1:1
3:1:1
Compound 32 cyproconazole trifloxystrobin 1:1:1 2:1:1
3:1:1
Compound 32 cyproconazole bixafen 1:1:2 2:1:2
3:1:2
Compound 32 cyproconazole boscalid 1:1:2 2:1:2
3:1:2
Compound 32 cyproconazole cyflufenamid 1:2:1 2:2:1
3:2:1
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
173
Component (a) Component (b) Illustrative Ratios(*)
Compound 32 cyproconazole fluopyram 1:1:2
2:1:2 3:1:2
Compound 32 cyproconazole isopyrazam 1:1:2
2:1:2 3:1:2
Compound 32 cyproconazole metrafenone 1:1:2
2:1:2 3:1:2
Compound 32 cyproconazole penthiopyrad 1:1:2
2:1:2 3:1:2
Compound 32 cyproconazole proquinazid 1:1:1
2:1:1 3:1:1
Compound 32 cyproconazole pyriofenone 1:1:2
2:1:2 3:1:2
Compound 32 cyproconazole quinoxyfen 1:1:1
2:1:1 3:1:1
Compound 32 cyproconazole sedaxane 1:1:2
2:1:2 3:1:2
Compound 32 cyproconazole picoxystrobin proquinazid 1:1:1:1
2:1:1:1 3:1:1:1
Compound 32 cyproconazole trifloxystrobin proquinazid
1:1:1:1 2:1:1:1 3:1:1:1
Compound 32 difenconazole azoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 difenconazole kresoxim-methyl
1:1:1 2:1:1 3:1:1
Compound 32 difenconazole picoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 difenconazole pyraclostrobin 1:1:1
2:1:1 3:1:1
Compound 32 difenconazole pyrametostrobin
1:1:1 2:1:1 3:1:1
Compound 32 difenoconazole pyraoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 difenconazole trifloxystrobin
1:1:1 2:1:1 3:1:1
Compound 32 difenconazole bixafen 1:1:2
2:1:2 3:1:2
Compound 32 difenconazole boscalid 1:1:2
2:1:2 3:1:2
Compound 32 difenconazole cyflufenamid 1:2:1
2:2:1 3:2:1
Compound 32 difenconazole fluopyram 1:1:2
2:1:2 3:1:2
Compound 32 difenconazole isopyrazam 1:1:2
2:1:2 3:1:2
Compound 32 difenconazole metrafenone 1:1:2
2:1:2 3:1:2
Compound 32 difenconazole penthiopyrad 1:1:2
2:1:2 3:1:2
Compound 32 difenconazole proquinazid 1:1:1
2:1:1 3:1:1
Compound 32 difenconazole pyriofenone 1:1:2
2:1:2 3:1:2
Compound 32 difenconazole quinoxyfen 1:1:1
2:1:1 3:1:1
Compound 32 difenconazole sedaxane 1:1:2
2:1:2 3:1:2
Compound 32 difenconazole picoxystrobin proquinazid 1:1:1:1
2:1:1:1 3:1:1:1
Compound 32 difenconazole trifloxystrobin proquinazid
1:1:1:1 2:1:1:1 3:1:1:1
Compound 32 epoxiconazole azoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 epoxiconazole kresoxim-methyl
1:1:1 2:1:1 3:1:1
Compound 32 epoxiconazole picoxystrobin 1:1:1
2:1:1 3:1:1
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
174
Component (a) Component (b) Illustrative Ratios(*)
Compound 32 epoxiconazole pyraclostrobin 1:1:1
2:1:1 3:1:1
Compound 32 epoxiconazole pyrametostrobin 1:1:1
2:1:1 3:1:1
Compound 32 epoxiconazole pyraoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 epoxiconazole trifloxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 epoxiconazole bixafen 1:1:2 2:1:2
3:1:2
Compound 32 epoxiconazole boscalid 1:1:2 2:1:2
3:1:2
Compound 32 epoxiconazole cyflufenamid 1:2:1
2:2:1 3:2:1
Compound 32 epoxiconazole fluopyram 1:1:2 2:1:2
3:1:2
Compound 32 epoxiconazole isopyrazam 1:1:2
2:1:2 3:1:2
Compound 32 epoxiconazole metrafenone 1:1:2
2:1:2 3:1:2
Compound 32 epoxiconazole penthiopyrad 1:1:2
2:1:2 3:1:2
Compound 32 epoxiconazole proquinazid 1:1:1
2:1:1 3:1:1
Compound 32 epoxiconazole pyriofenone 1:1:2
2:1:2 3:1:2
Compound 32 epoxiconazole quinoxyfen 1:1:1
2:1:1 3:1:1
Compound 32 epoxiconazole sedaxane 1:1:2 2:1:2
3:1:2
Compound 32 epoxiconazole picoxystrobin
proquinazid .. 1:1:1:1 .. 2:1:1:1 .. 3:1:1:1
Compound 32 epoxiconazole trifloxystrobin
proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 32 metconazole azoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 metconazole kresoxim-methyl 1:1:1
2:1:1 3:1:1
Compound 32 metconazole picoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 metconazole pyraclostrobin 1:1:1
2:1:1 3:1:1
Compound 32 metconazole pyrametostrobin 1:1:1
2:1:1 3:1:1
Compound 32 metconazole pyraoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 metconazole trifloxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 metconazole bixafen 1:1:2 2:1:2
3:1:2
Compound 32 metconazole boscalid 1:1:2 2:1:2
3:1:2
Compound 32 metconazole cyflufenamid 1:2:1
2:2:1 3:2:1
Compound 32 metconazole fluopyram 1:1:2 2:1:2
3:1:2
Compound 32 metconazole isopyrazam 1:1:2
2:1:2 3:1:2
Compound 32 metconazole metrafenone 1:1:2
2:1:2 3:1:2
Compound 32 metconazole penthiopyrad 1:1:2
2:1:2 3:1:2
Compound 32 metconazole proquinazid 1:1:1
2:1:1 3:1:1
Compound 32 metconazole pyriofenone 1:1:2
2:1:2 3:1:2
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
175
Component (a) Component (b) Illustrative Ratios(*)
Compound 32 metconazole quinoxyfen 1:1:1
2:1:1 3:1:1
Compound 32 metconazole sedaxane 1:1:2 2:1:2
3:1:2
Compound 32 metconazole picoxystrobin
proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 32 metconazole trifloxystrobin
proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 32 myclobutanil azoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 myclobutanil kresoxim-methyl 1:1:1
2:1:1 3:1:1
Compound 32 myclobutanil picoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 myclobutanil pyraclostrobin 1:1:1
2:1:1 3:1:1
Compound 32 myclobutanil pyrametostrobin 1:1:1
2:1:1 3:1:1
Compound 32 myclobutanil pyraoxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 myclobutanil trifloxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 myclobutanil bixafen 1:1:2 2:1:2
3:1:2
Compound 32 myclobutanil boscalid 1:1:2 2:1:2
3:1:2
Compound 32 myclobutanil cyflufenamid 1:2:1
2:2:1 3:2:1
Compound 32 myclobutanil fluopyram 1:1:2 2:1:2
3:1:2
Compound 32 myclobutanil isopyrazam 1:1:2
2:1:2 3:1:2
Compound 32 myclobutanil metrafenone 1:1:2
2:1:2 3:1:2
Compound 32 myclobutanil penthiopyrad 1:1:2
2:1:2 3:1:2
Compound 32 myclobutanil proquinazid 1:1:1
2:1:1 3:1:1
Compound 32 myclobutanil pyriofenone 1:1:2
2:1:2 3:1:2
Compound 32 myclobutanil quinoxyfen 1:1:1
2:1:1 3:1:1
Compound 32 myclobutanil sedaxane 1:1:2 2:1:2
3:1:2
Compound 32 myclobutanil picoxystrobin
proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 32 myclobutanil trifloxystrobin
proquinazid 1:1:1:1 2:1:1:1 3:1:1:1
Compound 32 prothioconazole azoxystrobin 1:1:1 2:1:1 3:1:1
Compound 32 prothioconazole kresoxim-methyl 1:1:1 2:1:1 3:1:1
Compound 32 prothioconazole picoxystrobin 1:1:1 2:1:1 3:1:1
Compound 32 prothioconazole pyraclostrobin 1:1:1 2:1:1 3:1:1
Compound 32 prothioconazole pyrametostrobin 1:1:1 2:1:1 3:1:1
Compound 32 prothioconazole pyraoxystrobin 1:1:1 2:1:1 3:1:1
Compound 32 prothioconazole trifloxystrobin 1:1:1
2:1:1 3:1:1
Compound 32 prothioconazole bixafen 1:1:2 2:1:2 3:1:2
Compound 32 prothioconazole boscalid 1:1:2 2:1:2 3:1:2
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
176
Component (a) Component (b) Illustrative Ratios(*)
Compound 32 prothioconazole cyflufenamid 1:2:1 2:2:1
3:2:1
Compound 32 prothioconazole fluopyram 1:1:2 2:1:2
3:1:2
Compound 32 prothioconazole isopyrazam 1:1:2 2:1:2
3:1:2
Compound 32 prothioconazole metrafenone 1:1:2 2:1:2
3:1:2
Compound 32 prothioconazole penthiopyrad 1:1:2 2:1:2
3:1:2
Compound 32 prothioconazole proquinazid 1:1:1 2:1:1
3:1:1
Compound 32 prothioconazole pyriofenone 1:1:2 2:1:2
3:1:2
Compound 32 prothioconazole quinoxyfen 1:1:1 2:1:1
3:1:1
Compound 32 prothioconazole sedaxane 1:1:2 2:1:2
3:1:2
Compound 32 prothioconazole picoxystrobin proquinazid
1:1:1:1 2:1:1:1 3:1:1:1
Compound 32 prothioconazole trifloxystrobin proquinazid
1:1:1:1 2:1:1:1 3:1:1:1
Compound 32 tebuconazole azoxystrobin 1:1:1 2:1:1
3:1:1
Compound 32 tebuconazole kresoxim-methyl 1:1:1 2:1:1
3:1:1
Compound 32 tebuconazole picoxystrobin 1:1:1 2:1:1
3:1:1
Compound 32 tebuconazole pyraclostrobin 1:1:1 2:1:1
3:1:1
Compound 32 tebuconazole pyrametostrobin 1:1:1 2:1:1
3:1:1
Compound 32 tebuconazole pyraoxystrobin 1:1:1 2:1:1
3:1:1
Compound 32 tebuconazole trifloxystrobin 1:1:1 2:1:1
3:1:1
Compound 32 tebuconazole bixafen 1:1:2 2:1:2
3:1:2
Compound 32 tebuconazole boscalid 1:1:2 2:1:2
3:1:2
Compound 32 tebuconazole cyflufenamid 1:2:1 2:2:1
3:2:1
Compound 32 tebuconazole fluopyram 1:1:2 2:1:2
3:1:2
Compound 32 tebuconazole isopyrazam 1:1:2 2:1:2
3:1:2
Compound 32 tebuconazole metrafenone 1:1:2 2:1:2
3:1:2
Compound 32 tebuconazole penthiopyrad 1:1:2 2:1:2
3:1:2
Compound 32 tebuconazole proquinazid 1:1:1 2:1:1
3:1:1
Compound 32 tebuconazole pyriofenone 1:1:2 2:1:2
3:1:2
Compound 32 tebuconazole quinoxyfen 1:1:1 2:1:1
3:1:1
Compound 32 tebuconazole sedaxane 1:1:2 2:1:2
3:1:2
Compound 32 tebuconazole picoxystrobin proquinazid
1:1:1:1 2:1:1:1 3:1:1:1
Compound 32 tebuconazole trifloxystrobin proquinazid
1:1:1:1 2:1:1:1 3:1:1:1
(*) Ratios of Component (a) relative to Component (b) in sequence, by weight.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
177
Tables C2 through C21 are each constructed the same as Table Cl above except
that entries
below the "Component (a)" column heading are replaced with the respective
Component (a)
Column Entry shown below. Thus, for example, in Table C2 the entries below the
"Component
(a)" column heading all recite "Compound 64", and the first line in below the
column headings in
Table C2 specifically discloses a mixture of Compound 64 with cyproconazole
and azoxystrobin,
and the illustrative weight ratios of 1:1:1,
2:1:1 and 3:1:1 of
Compound 64:cyproconazole:azoxystrobin. Tables C3 through C21 are constructed
similarly.
Table Number Component (a) Column Entry Table Number
Component (a) Column Entry
C2 Compound 64 C12 Compound 221
C3 Compound 71 C13 Compound 229
C4 Compound 126 C14 Compound 231
C5 Compound 127 C15 Compound 262
C6 Compound 132 C16 Compound 263
C7 Compound 162 C17 Compound 265
C8 Compound 163 C18 Compound 297
C9 Compound 171 C19 Compound 330
C10 Compound 186 C20 Compound 331
C11 Compound 218 C21 Compound 364
Of note is a composition of the present invention comprising a compound of
Formula 1 (or
an N-oxide or salt thereof) with at least one other fungicidal compound that
has a different site of
action from the compound of Formula 1. In certain instances, a combination
with at least one
other fungicidal compound having a similar spectrum of control but a different
site of action will
be particularly advantageous for resistance management. Thus, a composition of
the present
invention can advantageously comprise at least one fungicidal active compound
selected from the
group consisting of (b 1) through (b54) as described above, having a similar
spectrum of control
but a different site of action.
Compositions of component (a), or component (a) with component (b), can be
further mixed
with one or more other biologically active compounds or agents including
insecticides,
nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth
regulators such as
insect molting inhibitors and rooting stimulants, chemosterilants,
semiochemicals, repellents,
attractants, pheromones, feeding stimulants, plant nutrients, other
biologically active compounds
or entomopathogenic bacteria, virus or fungi to form a multi-component
pesticide giving an even
broader spectrum of agricultural protection. Thus the present invention also
pertains to a
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
178
composition comprising a fungicidally effective amount of component (a), or a
mixture of
component (a) with component (b), and a biologically effective amount of at
least one additional
biologically active compound or agent and can further comprise at least one of
a surfactant, a solid
diluent or a liquid diluent. The other biologically active compounds or agents
can also be
separately formulated in compositions comprising at least one of a surfactant,
solid or liquid
diluent. For compositions of the present invention, one or more other
biologically active
compounds or agents can be formulated together with one or both of components
(a) and (b) to
form a premix, or one or more other biologically active compounds or agents
can be formulated
separately from components (a) and (b) and the formulations combined together
before
application (e.g., in a spray tank) or, alternatively, applied in succession.
Examples of such biologically active compounds or agents with which
compositions of
component (a), or component (a) with component (b), can be formulated are:
insecticides such as
abamectin, acephate, acequinocyl, acetamiprid, acrinathrin, acynonapyr,
afidopyropen
(R3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3- Rcyclopropylcarbonyl)oxyl -1,3 ,4 ,4a,5
,6,6a,12,12a,12b -
decahydro-6,12-dihydroxy-4,6a,12b-trimethy1-11-oxo-9-(3-pyridiny1)-2H,11H-
naphtho [2,1-
b[pyrano [3,4-e[pyran-4-yll methyl cyclopropanecarboxylate), amidoflumet,
amitraz, avermectin,
azadirachtin, azinphos-methyl, benfuracarb, bensultap, benzpyrimoxan,
bifenthrin, kappa-
bifenthrin, bifenazate, bistrifluron, borate, broflanilide, buprofezin,
cadusafos, carbaryl,
carbofuran, cartap, carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron,
chloroprallethrin,
chlorpyrifos, chlorpyrifos-e, chlorpyrifos-methyl, chromafenozide,
clofentezin, chloroprallethrin,
clothianidin, cyantraniliprole
(3 -bromo- 1-(3 -chloro-2-pyridiny1)-N- [4-cyano-2-methy1-6-
[(methylamino)carbonyl[phenyll-1H-pyrazole-5-carboxamide), cyclaniliprole (3-
bromo-N- [2-
bromo-4-chloro-6- [[(1-cyclopropylethyl)amino[carbonyl[phenyll -1-(3-chloro-2-
pyridiny1)-1H-
pyrazole-5-carboxamide), cycloprothrin, cycloxaprid ((5S,8R)- 1- [(6-chloro-3-
pyridinyl)methyl]-
2,3 ,5,6,7 ,8-hexahydro -9-nitro-5,8-Epoxy-1H-imidazo [1,2-a] azepine),
cyenopyrafen,
cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalodiamide, cyhalothrin, gamma-
cyhalothrin,
lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin,
cyromazine,
deltamethrin, diafenthiuron, diazinon, dicloromesotiaz, dieldrin,
diflubenzuron, dimefluthrin,
dimehypo, dimethoate, dimpropyridaz, dinotefuran, diofenolan, emamectin,
emamectin benzoate,
endosulfan, esfenvalerate, ethiprole, etofenprox, epsilon-metofluthrin,
etoxazole, fenbutatin
oxide, fenitrothion, fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate,
fipronil, flometoquin (2-
ethy1-3,7-dimethy1-644-(trifluoromethoxy)phenoxyl -4-quinolinyl methyl
carbonate), flonicamid,
fluazaindolizine, flubendiamide, flucythrinate, flufenerim, flufenoxuron,
flufenoxystrobin
(methyl
(aE)-2-[[2-chloro-4-(trifluoromethyl)phenoxy[methyll-a-
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
179
(methoxymethylene)benzeneacetate), fluensulfone
(5- chloro-2- [(3 ,4,4-trifluoro-3 -buten- 1-
yl)sulfonyl] thiazole), fluhexafon, fluopyram, flupiprole
(1- [2,6-dichloro-4-
(trifluoromethyl)phenyl] -5- [(2-methy1-2-propen-1-y1)amino] -4-
[(trifluoromethyl) sulfinyl] - 1H-
pyrazole-3 -c arbonitrile), flupyradifurone
(4- [[(6-chloro-3 -pyridinyl)methyl] (2,2-
difluoroethyl)amino]-2(5H)-furanone), flupyrimin, fluvalinate, tau-
fluvalinate, fluxametamide,
fonophos, formetanate, fosthiazate, gamma-cyhalothrin, halofenozide,
heptafluthrin ([2,3,5,6-
tetrafluoro-4- (methoxymethyl)phenyl] methyl 2,2-dimethy1-3- [(1Z)-3 ,3 ,3 -
trifluoro- 1-propen- 1-
yl]cyclopropanec arboxylate), hexaflumuron, hexythiazox, hydramethylnon,
imidacloprid,
indoxacarb, insecticidal soaps, isofenphos, isocycloseram, kappa-tefluthrin,
lambda-cyhalothrin,
lufenuron, malathion, meperfluthrin ([2,3,5,6-tetrafluoro-4-
(methoxymethyl)phenyl]methyl
(1R,3S)-3-(2,2-dichloroetheny1)-2,2-dimethylcyclopropanecarboxylate),
metaflumizone,
metaldehyde, methamidophos, methidathion, methiocarb, methomyl, methoprene,
methoxychlor,
metofluthrin, methoxyfenozide, epsilon-metofluthrin, epsilon-momfluorothrin,
monocrotophos,
monofluorothrin ([2,3,5 ,6-tetrafluoro-4-(methoxymethyl)phenyl] methyl 3 - (2-
cy ano- 1-propen- 1-
y1)-2,2-dimethylcyclopropanecarboxylate), nicotine, nitenpyram, nithiazine,
novaluron,
noviflumuron, oxamyl, oxazosulfyl, parathion, parathion-methyl, permethrin,
phorate, phosalone,
phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite,
protrifenbute,
pyflubumide
(1,3 ,5-trimethyl-N-(2-methyl- 1-oxopropy1)-N- [3 - (2-methylpropy1)-4-
[2,2,2-
trifluoro- 1-methoxy- 1- (trifluoromethyl)ethyl]phenyl] - 1H-pyrazole-4-c
arboxamide),
pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon,
pyriminostrobin
(methyl
(aE)-2-[[[2-[(2,4-dichlorophenyl)amino]-6-(trifluoromethyl)-4-
pyrimidinylloxylmethyl]-a-(methoxymethylene)benzeneacetate), pyriprole,
pyriproxyfen,
rotenone, ryanodine, silafluofen, spinetoram, spino sad, spirodiclofen,
spiromesifen, spiropidion,
spirotetramat, sulprofos , sulfoxaflor (N-[methyloxido [1- [6-
(trifluoromethyl)-3 -pyridinyl] ethyl] -
k4-sulfanylidene]cyanamide), tebufenozide, tebufenpyrad, teflubenzuron,
tefluthrin, kappa-
tefluthrin, terbufos, tetrachlorantraniliprole, tetrachlorvinphos,
tetramethrin, tetramethylfluthrin
( [2,3,5 ,6-tetrafluoro-4 -(methoxymethyl)phenyl] methyl
2,2,3,3-
tetramethylcyclopropanecarboxylate), tetraniliprole, thiacloprid,
thiamethoxam, thiodicarb,
thiosultap- sodium, tioxazafen (3 -phenyl-5 -(2-thieny1)-1,2,4 -
oxadiazole), tolfenpyrad,
.. tralomethrin, triazamate, trichlorfon, triflumezopyrim (2,4-dioxo-1-(5-
pyrimidinylmethyl)-3- [3-
(trifluoromethyl)phenyl] -2H-pyrido [1,2-c]pyrimidinium inner salt),
triflumuron, tyclopyrazoflor,
zeta-cypermethrin, Bacillus thuringiensis delta-endotoxins, entomopathogenic
bacteria,
entomopathogenic viruses or entomopathogenic fungi.
One embodiment of biological agents for mixing with compounds of this
disclosure include
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
180
entomopathogenic bacteria such as Bacillus thuringiensis, and the encapsulated
delta-endotoxins
of Bacillus thuringiensis such as MVP and MVPII bioinsecticides prepared by
the CellCap
process (CellCap , MVP and MVPII are trademarks of Mycogen Corporation,
Indianapolis,
Indiana, USA); entomopathogenic fungi such as green muscardine fungus; and
entomopathogenic
(both naturally occurring and genetically modified) viruses including
baculovirus,
nucleopolyhedro virus (NPV) such as Helicoverpa zea nucleopolyhedrovirus
(HzNPV),
Anagrapha falcifera nucleopolyhedrovirus (AfNPV); and granulosis virus (GV)
such as Cydia
pornonella granulosis virus (CpGV).
General references for these agricultural protectants (i.e. insecticides,
fungicides,
nematocides, acaricides, herbicides and biological agents) include The
Pesticide Manual, 13th
Edition, C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham,
Surrey, U.K., 2003 and
The BioPesticide Manual, 2nd Edition, L. G. Copping, Ed., British Crop
Protection Council,
Farnham, Surrey, U.K., 2001.
For embodiments where one or more of these various mixing partners are used,
the weight
ratio of these various mixing partners (in total) to component (a), or a
mixture of component (a)
with component (b), is generally between about 1:3000 and about 3000:1. Of
note are weight
ratios between about 1:100 and about 3000:1, or between about 1:30 and about
300:1 (for example
ratios between about 1:1 and about 30:1). It will be evident that including
these additional
components may expand the spectrum of diseases controlled beyond the spectrum
controlled by
component (a), or a mixture of component (a) with component (b).
Component (a) compounds and/or combinations thereof with component (b)
compounds
and/or one or more other biologically active compounds or agents can be
applied to plants
genetically transformed to express proteins toxic to invertebrate pests (such
as Bacillus
thuringiensis delta-endotoxins). The effect of the exogenously applied present
component (a)
alone or in combination with component (b) may be synergistic with the
expressed toxin proteins.
Of note is the combination or the composition comprising component (a), or
components
(a) and (b), as described in the Summary of the Invention further comprising
at least one
invertebrate pest control compound or agent (e.g., insecticide, acaricide). Of
particular note is a
composition comprising component (a) and at least one (i.e. one or more)
invertebrate pest control
compound or agent, which then can be subsequently combined with component (b)
to provide a
composition comprising components (a) and (b) and the one or more invertebrate
pest control
compounds or agents. Alternatively without first mixing with component (b), a
biologically
effective amount of the composition comprising component (a) with at least one
invertebrate pest
control agent can be applied to a plant or plant seed (directly or through the
environment of the
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
181
plant or plant seed) to protect the plant or plant seed from diseases caused
by fungal pathogens
and injury caused by invertebrate pests.
For embodiments where one or more of invertebrate pest control compounds are
used, the
weight ratio of these compounds (in total) to the component (a) compounds is
typically between
about 1:3000 and about 3000:1. Of note are weight ratios between about 1:300
and about 300:1
(for example ratios between about 1:30 and about 30:1). One skilled in the art
can easily determine
through simple experimentation the biologically effective amounts of active
ingredients necessary
for the desired spectrum of biological activity.
Of note is a composition of the present invention which comprises in addition
to a
component (a) compound, alone or in combination with component (b), at least
one invertebrate
pest control compound or agent selected from the group consisting abamectin,
acetamiprid,
acrinathrin, acynonapyr, afidopyropen, amitraz, avermectin, azadirachtin,
benfuracarb, bensultap,
bifenthrin, buprofezin, broflanilide, cadusafos, carbaryl, cartap,
chlorantraniliprole,
chloroprallethrin, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole,
cyclaniliprole,
cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin,
lambda-cyhalothrin,
cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin,
dieldrin,
dinotefuran, diofenolan, emamectin, endosulfan, epsilon-metofluthrin,
esfenvalerate, ethiprole,
etofenprox, etoxazole, fenitrothion, fenothiocarb, fenoxycarb, fenvalerate,
fipronil, flometoquin,
fluxametamide, flonicamid, flubendiamide, fluensulfone, flufenoxuron,
flufenoxystrobin,
flufensulfone, flupiprole, flupyrimin, flupyradifurone, fluvalinate,
formetanate, fosthiazate,
gamma-cyhalothrin, heptafluthrin, hexaflumuron, hydramethylnon, imidacloprid,
indoxacarb,
isocycloseram, kappa-tefluthrin, lambda-cyhalothrin, lufenuron, meperfluthrin,
metaflumizone,
methiodicarb, methomyl, methoprene, methoxyfenozide, metofluthrin,
monofluorothrin,
nitenpyram, nithiazine, novaluron, oxamyl, pyflubumide, pymetrozine,
pyrethrin, pyridaben,
pyridalyl, pyriminostrobin, pyriproxyfen, ryanodine, spinetoram, spinosad,
spirodiclofen,
spiromesifen, spirotetramat, sulfoxaflor, tebufenozide, tetramethrin,
tetramethylfluthrin,
thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin,
triazamate,
triflumezopyrim, triflumuron, tyclopyrazoflor, zeta-cypermethrin, Bacillus
thuringiensis delta-
endotoxins, all strains of Bacillus thuringiensis and all strains of nucleo
polyhedrosis viruses.
In certain instances, combinations of a a component (a) compound of this
invention, alone
or in mixture with component (b), with other biologically active (particularly
fungicidal)
compounds or agents (i.e. active ingredients) can result in a greater-than-
additive (i.e. synergistic)
effect. Reducing the quantity of active ingredients released in the
environment while ensuring
effective pest control is always desirable. When an enhanced effect of
fungicidal active
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
182
ingredients occurs at application rates giving agronomically satisfactory
levels of fungal control,
such combinations can be advantageous for reducing crop production cost and
decreasing
environmental load.
Table D1 lists specific combinations of invertebrate pest control agents with
Compound 32
(compound numbers refer to compounds in Index Tables A through L) as a
component (a)
compound illustrative of mixtures and compositions comprising these active
ingredients and
methods using them according to the present invention. The second column of
Table D1 lists the
specific invertebrate pest control agents (e.g., "Abamectin" in the first
line). The third column of
Table D1 lists the mode of action (if known) or chemical class of the
invertebrate pest control
agents. The fourth column of Table D1 lists embodiment(s) of ranges of weight
ratios for rates at
which the invertebrate pest control agent is typically applied relative to
Compound 32 alone or in
combination with component (b) (e.g., "50:1 to 1:50" of abamectin relative to
a Compound 32 by
weight). Thus, for example, the first line of Table D1 specifically discloses
the combination of
Compound 32 with abamectin is typically applied in a weight ratio between 50:1
to 1:50. The
remaining lines of Table D1 are to be construed similarly. Thus, for example,
the first line of
Table D1 specifically discloses the combination of Compound 32 with abamectin
is typically
applied in a weight ratio between 50:1 to 1:50. The remaining lines of Table
D1 are to be
construed similarly.
Table D1
Invertebrate Pest Control Typical
Table Number Agent Mode of Action or Chemical Class
Weight Ratio
Compound 32 Abamectin macrocyclic lactones
50:1 to 1:50
Compound 32 Acetamiprid neonicotinoids
150:1 to 1:200
Compound 32 Amitraz octopamine receptor ligands
200:1 to 1:100
Compound 32 Avermectin macrocyclic lactones
50:1 to 1:50
Compound 32 Az adirachtin ecdysone agonists
100:1 to 1:120
Compound 32 Beta-cyfluthrin sodium channel modulators
150:1 to 1:200
Compound 32 Bifenthrin sodium channel modulators
100:1 to 1:10
Compound 32 Buprofezin chitin synthesis inhibitors
500:1 to 1:50
Compound 32 Cartap nereistoxin analogs
100:1 to 1:200
Compound 32 Chlorantraniliprole ryanodine receptor ligands
100:1 to 1:120
mitochondrial electron transport
Compound 32 Chlorfenapyr
300:1 to 1:200
inhibitors
Compound 32 Chlorpyrifos cholinesterase inhibitors
500:1 to 1:200
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
183
Invertebrate Pest Control Typical
Table Number Agent Mode of Action or Chemical Class Weight
Ratio
Compound 32 Clothianidin neonicotinoids 100:1 to
1:400
Compound 32 Cyantraniliprole ryanodine receptor ligands 100:1 to
1:120
Compound 32 Cyfluthrin sodium channel modulators 150:1 to
1:200
Compound 32 Cyhalothrin sodium channel modulators 150:1 to
1:200
Compound 32 Cypermethrin sodium channel modulators 150:1 to
1:200
Compound 32 Cyromazine chitin synthesis inhibitors 400:1 to
1:50
Compound 32 Deltamethrin sodium channel modulators 50:1 to
1:400
Compound 32 Dieldrin cyclodiene insecticides 200:1 to
1:100
Compound 32 Dinotefuran neonicotinoids 150:1 to
1:200
Compound 32 Diofenolan molting inhibitor 150:1 to
1:200
Compound 32 Emamectin macrocyclic lactones 50:1 to
1:10
Compound 32 Endosulfan cyclodiene insecticides 200:1 to
1:100
Compound 32 Esfenvalerate sodium channel modulators 100:1 to
1:400
GABA-regulated chloride channel
Compound 32 Ethiprole 200:1 to
1:100
blockers
Compound 32 Fenothiocarb 150:1 to
1:200
Compound 32 Fenoxycarb juvenile hormone mimics 500:1 to
1:100
Compound 32 Fenvalerate sodium channel modulators 150:1 to
1:200
GABA-regulated chloride channel
Compound 32 Fipronil 150:1 to
1:100
blockers
Compound 32 Flonicamid 200:1 to
1:100
Compound 32 Flubendiamide ryanodine receptor ligands 100:1 to
1:120
Compound 32 Flufenoxuron chitin synthesis inhibitors 200:1 to
1:100
Compound 32 Hexaflumuron chitin synthesis inhibitors 300:1 to
1:50
mitochondrial electron transport
Compound 32 Hydramethylnon 150:1 to
1:250
inhibitors
Compound 32 Imidacloprid neonicotinoids 1000:1
to 1:1000
Compound 32 Indoxacarb sodium channel modulators 200:1 to
1:50
Compound 32 Lambda-cyhalothrin sodium channel modulators 50:1 to
1:250
Compound 32 Lufenuron chitin synthesis inhibitors 500:1 to
1:250
Compound 32 Meperfluthrin sodium channel modulators 100:1 to
1:400
Compound 32 Metaflumizone 200:1 to
1:200
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
184
Invertebrate Pest Control Typical
Table Number Agent Mode of Action or Chemical Class Weight
Ratio
Compound 32 Methomyl cholinesterase inhibitors 500:1 to
1:100
Compound 32 Methoprene juvenile hormone mimics 500:1 to
1:100
Compound 32 Methoxyfenozide ecdysone agonists 50:1 to
1:50
Compound 32 Nitenpyram neonicotinoids 150:1
to 1:200
Compound 32 Nithiazine neonicotinoids 150:1
to 1:200
Compound 32 Novaluron chitin synthesis inhibitors 500:1 to
1:150
Compound 32 Oxamyl cholinesterase inhibitors 200:1 to
1:200
Compound 32 Pymetrozine 200:1 to
1:100
Compound 32 Pyrethrin sodium channel modulators 100:1 to
1:10
mitochondrial electron transport
Compound 32 Pyridaben 200:1 to
1:100
inhibitors
Compound 32 Pyridalyl 200:1 to
1:100
Compound 32 Pyriproxyfen juvenile hormone mimics 500:1 to
1:100
Compound 32 Ryanodine ryanodine receptor ligands 100:1 to
1:120
Compound 32 Spinetoram macrocyclic lactones 150:1 to
1:100
Compound 32 Spinosad macrocyclic lactones 500:1 to
1:10
Compound 32 Spirodiclofen lipid biosynthesis inhibitors 200:1 to
1:200
Compound 32 Spiromesifen lipid biosynthesis inhibitors 200:1 to
1:200
Compound 32 Sulfoxaflor 200:1 to
1:200
Compound 32 Tebufenozide ecdysone agonists 500:1 to
1:250
Compound 32 Tetramethylfluthrin sodium channel modulators 100:1 to
1:40
Compound 32 Thiacloprid neonicotinoids 100:1
to 1:200
Compound 32 Thiamethoxam neonicotinoids 1250:1
to 1:1000
Compound 32 Thiodicarb cholinesterase inhibitors 500:1 to
1:400
Compound 32 Thiosultap-sodium 150:1 to
1:100
Compound 32 Tralomethrin sodium channel modulators 150:1 to
1:200
Compound 32 Triazamate cholinesterase inhibitors 250:1 to
1:100
Compound 32 Triflumuron chitin synthesis inhibitors 200:1 to
1:100
Compound 32 Bacillus thuringiensis biological agents 50:1 to
1:10
Bacillus thuringiensis delta-
Compound 32 biological agents 50:1 to 1:10
endotoxin
Compound 32 NPV (e.g., Gemstar) biological agents 50:1 to
1:10
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
185
Tables D2 through D21 are each constructed the same as Table D1 above except
that entries
below the "Component (a)" column heading are replaced with the respective
Component (a)
Column Entry shown below. Thus, for example, in Table D2 the entries below the
"Component
(a)" column heading all recite "Compound 64", and the first line in below the
column headings in
Table D2 specifically discloses a mixture of Compound 64 with abamectin.
Tables D3 through
D21 are constructed similarly.
Table Number Component (a) Column Entry Table Number
Component (a) Column Entry
D2 Compound 64 D12 Compound 221
D3 Compound 71 D13 Compound 229
D4 Compound 126 D14 Compound 231
D5 Compound 127 D15 Compound 262
D6 Compound 132 D16 Compound 263
D7 Compound 162 D17 Compound 265
D8 Compound 163 D18 Compound 297
D9 Compound 171 D19 Compound 330
D10 Compound 186 D20 Compound 331
Dll Compound 218 D21 Compound 364
Compositions comprising compounds of Formula 1 useful for seed treatment can
further
comprise bacteria and fungi that have the ability to provide protection from
the harmful effects of
plant pathogenic fungi or bacteria and/or soil born animals such as nematodes.
Bacteria exhibiting
nematicidal properties may include but are not limited to Bacillus firrnus,
Bacillus cereus,
Bacillius subtiliis and Pasteuria penetrans. A suitable Bacillus firrnus
strain is strain CNCM I-
1582 (GB-126) which is commercially available as BioNemTm. A suitable Bacillus
cereus strain
is strain NCMM 1-1592. Both Bacillus strains are disclosed in US 6,406,690.
Other suitable
bacteria exhibiting nematicidal activity are B. arnyloliquefaciens IN937a and
B. subtilis strain
GB03. Bacteria exhibiting fungicidal properties may include but are not
limited to B. purnilus
strain GB 34. Fungal species exhibiting nematicidal properties may include but
are not limited to
Myrotheciurn verrucaria, Paecilornyces lilacinus and Purpureocilliurn
lilacinurn.
Seed treatments can also include one or more nematicidal agents of natural
origin such as
the elicitor protein called harpin which is isolated from certain bacterial
plant pathogens such as
Erwinia arnylovora. An example is the Harpin-N-Tek seed treatment technology
available as N-
HibitTM Gold CST.
Seed treatments can also include one or more species of legume-root nodulating
bacteria
such as the microsymbiotic nitrogen-fixing bacteria Bradyrhizobiurn
japonicurn. These
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
186
inocculants can optionally include one or more lipo-chitooligosaccharides
(LC0s), which are
nodulation (Nod) factors produced by rhizobia bacteria during the initiation
of nodule formation
on the roots of legumes. For example, the Optimize brand seed treatment
technology
incorporates LCO Promoter TechnologyTm in combination with an inocculant.
Seed treatments can also include one or more isoflavones which can increase
the level of
root colonization by mycorrhizal fungi. Mycorrhizal fungi improve plant growth
by enhancing
the root uptake of nutrients such as water, sulfates, nitrates, phosphates and
metals. Examples of
isoflavones include, but are not limited to, genistein, biochanin A,
formononetin, daidzein,
glycitein, hesperetin, naringenin and pratensein. Formononetin is available as
an active ingredient
in mycorrhizal inocculant products such as PHC Colonize AG.
Seed treatments can also include one or more plant activators that induce
systemic acquired
resistance in plants following contact by a pathogen. An example of a plant
activator which
induces such protective mechanisms is acibenzolar-S-methyl.
In the present fungicidal compositions, the Formula 1 compounds of component
(a) can
work synergically with the additional fungicidal compounds of component (b) to
provide such
beneficial results as broadening the spectrum of plant diseases controlled,
extending duration of
preventative and curative protection, and suppressing proliferation of
resistant fungal pathogens.
In particular embodiments, compositions are provided in accordance with this
invention that
comprise proportions of component (a) and component (b) that are especially
useful for
controlling particular fungal diseases (such as Alternaria solani, Blurneria
grarninis f. sp. tritici,
Botrytis cinerea, Puccinia recondita f. sp. tritici, Rhizoctonia solani,
Septoria nodorurn, Septoria
tritici).
Mixtures of fungicides may also provide significantly better disease control
than could be
predicted based on the activity of the individual components. This synergism
has been described
as "the cooperative action of two components of a mixture, such that the total
effect is greater or
more prolonged than the sum of the effects of the two (or more) taken
independently" (see P. M.
L. Tames, Neth. J. Plant Pathology 1964, 70, 73-80). In methods providing
plant disease control
in which synergy is exhibited from a combination of active ingredients (e.g.,
fungicidal
compounds) applied to the plant or seed, the active ingredients are applied in
a synergistic weight
ratio and synergistic (i.e. synergistically effective) amounts. Measures of
disease control,
inhibition and prevention cannot exceed 100%. Therefore expression of
substantial synergism
typically requires use of application rates of active ingredients wherein the
active ingredients
separately provide much less than 100% effect, so that their additive effect
is substantially less
than 100% to allow the possibility of increase in effect as result of
synergism. On the other hand,
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
187
application rates of active ingredients that are too low may show not show
much activity in
mixtures even with the benefit of synergism. One skilled in the art can easily
identify and optimize
through simple experimentation the weight ratios and application rates (i.e.
amounts) of fungicidal
compounds providing synergy.
The presence of a synergistic effect between two active ingredients was
established with the
aid of the Colby equation (see Colby, S. R. "Calculating Synergistic and
Antagonistic Responses
of Herbicide Combinations", Weeds, (1967), 15, 20-22):
p = A B _ [Axl
100
=
Using the method of Colby, the presence of a synergistic interaction between
two active
ingredients is established by first calculating the predicted activity, p, of
the mixture based on
activities of the two components applied alone. If p is lower than the
experimentally established
effect, synergism has occurred. In the equation above, A is the fungicidal
activity in percentage
control of one component applied alone at rate x. The B term is the fungicidal
activity in
percentage control of the second component applied at rate y. The equation
estimates p, the
expected fungicidal activity of the mixture of A at rate x with B at rate y if
their effects are strictly
additive and no interaction has occurred.
The following TESTS demonstrate the control efficacy of compounds of this
invention on
specific pathogens. The pathogen control protection afforded by the compounds
is not limited,
however, to these species. See Index Tables A through L below for compound
descriptions. The
following abbreviations are used in the Index Tables: Me means methyl, Et
means ethyl, n-Pr
means n-propyl, i-Pr means iso-propyl, c-Pr means cyclopropyl, n-Bu means n-
butyl, i-Bu means
iso-butyl, c-Bu means cyclobutyl, c-hexyl means cyclohexyl, Ph means phenyl,
Me0 means
methoxy and Et0 means ethoxy. The abbreviation "Cmpd. No." stands for
"Compound Number",
and the abbreviation "Ex." stands for "Example" and is followed by a number
indicating in which
example the compound is prepared. The abbreviation "m.p." stands for melting
point. The
numerical value reported in the column "MS" is the molecular weight of the
highest isotopic
abundance positively charged parent ion (M+1) formed by addition of H
(molecular weight of
1) to the molecule having the highest isotopic abundance, or the highest
isotopic abundance
negatively charged ion (M-1) formed by loss of H (molecular weight of 1). The
presence of
molecular ions containing one or more higher atomic weight isotopes of lower
abundance (e.g.,
37C1, 81Br) is not reported. The reported MS peaks were observed by mass
spectrometry using
electrospray ionization (ESI) or atmospheric pressure chemical ionization
(APCI).
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
188
INDEX TABLE A
0 A xCF3
HO OH
R13 I \
\ N,.
L
Cmpd. No. R13 L A NMR MS
1 (Ex. 1) Et0C(=0) CH2 OCH2 *
Et0C(=0) CH2 OCH(Me) *
35 Et0C(=0) CH(Me) OCH2 *
36 c-PrCH2NHC(=0) CH2 OCH2 * 400 (M+1)
37 Me0C(=0) CH2 OCH2 * 361 (M+1)
38 CH2=CHCF20C(=0) CH2 OCH2 423 (M+1)
39 i-PrOC(=0) CH2 OCH2 * 389 (M+1)
40 CH2=C(Me)CH20C(=0) CH2 OCH2 * 401 (M+1)
42 n-PrOC(=0) CH2 OCH2 * 389 (M+1)
43 CH2=CHCH20C(=0) CH2 OCH2 * 387 (M+1)
44 HCCCH20C(=0) CH2 OCH2 * 385 (M+1)
45 CF3CH20C(=0) CH2 OCH2 * 429 (M+1)
46 CF3CF2CH20C(=0) CH2 OCH2 * 479 (M+1)
47 PhCH20C(=0) CH2 OCH2 * 437 (M+1)
48 CH3(CH2)50C(=0) CH2 OCH2 * 431 (M+1)
49 3,4-di-CI-PhCH20C(=0) CH2 OCH2 * 505 (M+1)
50 3,4-di-F-PhCH20C(=0) CH2 OCH2 * 473 (M+1)
51 Et0C(=0) CH2 CH(OH)CH2 *
66 Et0C(=0) CH2 CH2CH2 * 355 (M+1)
131 Et0C(=0) CH2CH2 OCH2 *
206 I\IC CH2 OCH2 *
227 Et0C(=0) CH2 OCF2 *
286 Et0C(=0) (CH2)3 OCH2 * 403 (M+1)
322 Br CH2 OCH2 * 383 (M+1)
329 HOC(=0) CH2 OCH2 * 327 (M-1)
381 Et0C(=0) CH2 N(CN)CH2 381 (M+1)
388 CF3 CH2 OCH2 351 (M-1)
389 NO2 CH2 OCH2 346 (M-1)
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
189
*See Index Table M for 19F NMR data.
INDEX TABLE Al
HO /OH
3 O
_C---N 2 0 CF3
n, 13
rk \ it
L
6 (R8)cl
Cmpd. No. R13 L (R8)ci NMR MS
264 Et0C(=0) CH2 3-F *
376 Et0C(=0) CH2 2-F
393 (M+1)
409 Et0C(=0) CH2 3-I
501 (M+1)
431 Et0C(=0) CH2 2,3-di-
F 411 (M+1)
444 Et0C(=0) CH2 3-Me
389 (M+1)
455 NO2 CH2 3-F 346 (M-
1)
456 CF3 CH2 3-F 369 (M-
1)
459 Et0C(=0) CH2 3-C1
409 (M+1)
465 Et0C(=0) CH2 2,3,5,6-
tetrafluoro 447 (M+1)
*See Index Table M for 19F NMR data.
5 INDEX TABLE A2
R13
A 7 CF3
....---.L 1101 H0 H
S L
Cmpd. No. R13 L A MS m.p. ( C)
68 CF3CH2NHC(=0) CH2 OCH2 445 (M+1) 116-120
69 c-PrCH2NHC(=0) CH2 OCH2 417 (M+1)
0
F
135 F \r,N,..k cH2 OCH2 453 (M+1)
136 Et0C(=0) CH2 OCH2 392 (M+1)
0
215
N *---4 CH2 OCH2 403 (M+1) 140-144
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
190
Cmpd. No. R13 L A MS m.p. ( C)
223 MeOCH2CH2NHC(=0) CH2 OCH2 421 (M+1)
INDEX TABLE B
0 A xCF3
HO OH
EL
A dash "¨" in the L column means that L is a direct bond.
Cmpd. No. E L A NMR MS
m.p. ( C)
2 CF3C(OH)2CH20 OCH2 *
105-109
29 CH3CH2S(=0)2 CH2 OCH2 *
30 1-indoly1 CH2 CH2CH2 332 (M+1)
31 MeS(=0)2 OCH2 *
102-106
33 Me0C(=0)NHN=CH OCH2 *
140-145
34 Me2NS(=0)2 OCH2 *
142-146
41 3-(Me2NC(=0))-4,5-dihydro-5-isoxazoly1 ¨ OCH2 *
80 CH3C(=0) OCH2 *
97 Et0C(=0)CH=CHCH20 OCH2 *
142 I\TC OCH2 *
177 HC(=0) OCH2 *
229 Me0C(=0) OCH2 279 (M-1)
233 3-(Et0C(=0))-1H-pyrazol-1-y1 CH2 OCH2 *
234 5-(Et0C(=0))-1H-pyrazol-1-y1 CH2 OCH2 *
247 5-(c-PrCH2NHC(=0))-2-oxazoly1 CH2 OCH2 401
(M+1)
256 5-(c-PrCH2NHC(=0))-2-thiazoly1 CH2 OCH2
417 (M+1) 126-130
274 5-(CF3CH2NHC(=0))-2-oxazoly1 CH2 OCH2 429 (M+1)
75-79
277 5-(CF3CH2NHC(=0))-2-thiazoly1 CH2 OCH2
445 (M+1) 110-114
280 NO2 OCH2 *
295 5-(F2CHCH2NHC(=0))-2-thiazoly1 CH2 OCH2 427
(M+1)
366 (Ex. 8) 4-(Et0C(=0))-1H-pyrazol-1-yl-
CH20 OCH2 **
369 CH3 ¨ OCH(C(=0)0Me *
0
384 Y---N--_ OCH2 320 (M+1)
H3C
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
191
Cmpd. No. E L A NMR MS
m.p. ( C)
387 CF3 OCH2 271 (M-1)
396 CH3 OCH2 *
432 Me0 CH2 OCH2 *
*See Index Table M for 19F NMR data.
**See Index Table N for 1H NMR data.
INDEX TABLE C
0 AxCF3
_C-N
RI 3 \ IV 0 0
L M
Cmpd. No. R13 L A M NMR MS
3 n-PrOC(=0) CH2 OCH2 CH2 * 415
(M+1)
4 Et0C(=0) CH2 OCH2 C(=0) * 415
(M+1)
6 Et0C(=0) CH2 OCH(Me) CH2 *
7 [Note 1] Et0C(=0) CH2 OCH2 CH(Me) *
8 [Note 2] Et0C(=0) CH2 OCH2 CH(Me) *
12 (Ex. 3) Et0C(=0) CH2 OCH2 C(Me)2 *
13 Me0C(=0) CH2 OCH2 CH2 * 387
(M+1)
14 i-PrOC(=0) CH2 OCH2 CH2 * 415
(M+1)
15 HCCCH20C(=0) CH2 OCH2 CH2 * 411
(M+1)
16 CH3(CH2)50C(=0) CH2 OCH2 CH2 * 457
(M+1)
17 3,4-di-Cl-PhCH20C(=0) CH2 OCH2 CH2 * 531
(M+1)
18 3,4-di-F-PhCH20C(=0) CH2 OCH2 CH2 * 499
(M+1)
26 Et0C(=0) CH(CH3) OCH2 CH2 * 413
(M-1)
32 (Ex. 2)
Et0C(=0) CH2 OCH2 CH2 *
and (Ex. 4)
67 Et0C(=0) CH2 CH2CH2 CH2 * 397
(M-1)
93 HOC(=0) CH2 OCH2 CH2 *
115 Et0C(=0) CH2 SCH2 CH2 417
(M+1)
125 n-BuOC(=0) CH2 OCH2 CH2 429
(M+1)
126 i-BuOC(=0) CH2 OCH2 CH2 * 429
(M+1)
127 c-PrCH20C(=0) CH2 OCH2 CH2 * 427
(M+1)
133 Et0C(=0) CH2CH2 OCH2 CH2 *
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
192
Cmpd. No. R13 L A M NMR MS
134 CF3CH20C(=0) CH2 OCH2 CH2 * 453
(M-1)
141 Et0C(=0) CH2 CH2OCH2 CH2 *
161 C1(CH2)30C(=0) CH2 OCH2 CH2 * 449
(M+1)
162 MeOCH2CH20C(=0) CH2 OCH2 CH2 * 431
(M+1)
163 CH3CCCH20C(=0) CH2 OCH2 CH2 * 425
(M+1)
164 I\TCCH2NHC(=0) CH2 OCH2 CH2 * 411
(M+1)
169 CH3C(=0)CH20C(=0) CH2 OCH2 CH2 * 429
(M+1)
170 PhC(=0)CH20C(=0) CH2 OCH2 CH2 * 491
(M+1)
171 I\TC(CH2)30C(=0) CH2 OCH2 CH2 * 440
(M+1)
172 I\TCCH20C(=0) CH2 OCH2 CH2 *
188 CH2=CHCH20C(=0) CH2 OCH2 CH2 413
(M+1)
197 CF3CH2NHC(=0) CH2 OCH2 CH2 * 454
(M+1)
198 Me2NC(=0) CH2 OCH2 CH2 * 400
(M+1)
199 2-pyridyl-CH20C(=0) CH2 OCH2 CH2 * 464
(M+1)
200 3-pyridyl-CH20C(=0) CH2 OCH2 CH2 * 464
(M+1)
201 4-pyridyl-CH20C(=0) CH2 OCH2 CH2 * 464
(M+1)
202 c-hexyl-C(=0)CH20C(=0) CH2 OCH2 CH2 * 497
(M+1)
203 Me0C(=0)CH20C(=0) CH2 OCH2 CH2 * 445
(M+1)
204 1,3-dioxolan-2-yl-CH20C(=0) CH2 OCH2 CH2 *
459 (M+1)
209 I\TC CH2 OCH2 CH2 *
228 CH2=C(CH3)CH20C(=0) CH2 OCH2 CH2 * 427
(M+1)
240 EtOCH2 CH2 OCH2 CH2 * 387
(M+1)
249 c-BuCH20C(=0) CH2 OCH2 CH2 * 441
(M+1)
272 c-hexyl-CH20C(=0) CH2 OCH2 CH2 * 469
(M+1)
284 c-pentyl-CH20C(=0) CH2 OCH2 CH2 * 455
(M+1)
285 [Note 4] CH3CH=CHCH20C(=0) CH2 OCH2 CH2 * 427
(M+1)
296 Et0C(=0) (CH2)3 OCH2 CH2 * 429
(M+1)
318 c-BuOC(=0) CH2 OCH2 CH2 * 427
(M+1)
319 Et0C(=0) CH2 OCF2 CH2 * 437
(M+1)
443 Et0C(=0) CH2 NHCH2 CH2 *
*See Index Table M for 19F NMR data.
Note 1: 87:13 mixture of diastereomers.
Note 2: 33:67 mixture of diastereomers.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
193
Note 4: 60:40 mixture of cis-trans isomers.
INDEX TABLE D
Et0 40/ oT
0
Cmpd. No. T NMR MS
HO\ ime
9
3
HO\ iNHOH
CF3
0
0)
CF3
21 400 (M+1)
H
On
52 )\--O
CF3
0
187 429 (M+1)
CH3
0
F3C
*See Index Table M for 19F NMR data.
5 INDEX TABLE E
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
194
0 AxCF3
0 0
E \_/
L
A dash "¨" in the L column means that L is a direct bond.
Cmpd. No. E L A NMR MS
22 3-(Me2NC(=0))-4,5-dihydro-5-isoxazoly1 ¨ OCH2 *
23 CH3CH2S(=0)2 CH2 OCH2 *
24 CH3S(=0)2 ¨ OCH2 *
25 (Me)2N5(=0)2 ¨ OCH2 *
27 Me0C(=0)NHN=CH ¨ OCH2 *
no
28 0.K.....
0¨ ¨ OCH2 *
F3C
76 i-BuS(=0)2NH CH2 OCH2 396 (M-1)
77 c-hexyl-NHC(=S)NH CH2 OCH2 419 (M+1)
78 Et0C(=0)NH CH2 OCH2 350 (M+1)
98 I\TC ¨ OCH2 * 274 (M+1)
112 i-BuOC(=0)NH CH2 OCH2 *
160 5-(Et0C(=0)-1-indazoly1 CH2 OCH2 *
166 NO2 ¨ OCH2 *
173 5-(CF3)-1,2,4-oxadiazol-3-y1 ¨ OCH2 385 (M+1)
174 NH2 CH2 OCH2 *
175 i-PrC(=0)NH CH2 OCH2 348 (M+1)
176 c-PrC(=0)NH CH2 OCH2 *
301
178 OH CH2 OCH2
(M+23)
179 3-CF3-PhC(=0)NH CH2 OCH2 *
189 Me0C(=0) ¨ OCH2 * 307 (M+1)
190 Ph ¨ OCH2 *
191 PhO ¨ OCH2 *
192 Ph CH2 OCH2 *
207 CF3S(=0)2NH CH2 OCH2 408 (M-1)
212 CF3CH2C(=0)NH CH2 OCH2 388 (M+1)
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
195
Cmpd. No. E L A NMR MS
214 MeOCH(CH3)C(=0)NH CH2 OCH2 *
232 3-(Et0C(=0))-1H-pyrazol-1-y1 CH2 OCH2 *
235 i-PrC(=0)N(OMe) CH2 OCH2 *
236 c-PrC(=0)N(OMe) CH2 OCH2 *
237 n-PrC(=0)N(OMe) CH2 OCH2 *
CH2 430
238 t-BuOC(=0)N(OMe) OCH2
(M+23)
239 I\TC CH2 OCH2 *
281 2-(MeS)-4-pyrimidinyl CH2 OCH2 387 (M+1)
282 2-(MeS(=0)2)-4-pyrimidinyl CH2 OCH2 419 (M+1)
283 2-(F2CHCH20)-4-pyrimidinyl CH2 OCH2 421 (M+1)
0
289 Et0"--- CH2 OCH2 *
IN 0
0
290 (-M-02N), --f)_ CH2 OCH2 *
IN 0
OCH2CH2Si(Me)3
314 N )N CH2 OCH2 457 (M+1)
LL
372 Y---N--_ ¨ OCH2 346 (M+1)
H3C
17
382 07----_-s--N ¨ OCH2 396 (M+1)
/
Et
0
411 >----N--- ¨ OCH2 375 (M+1)
Et¨NH
*See Index Table M for 19F NMR data.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
196
INDEX TABLE El
R13 4 1 A ........"õ.CF3
N"
1
Cmpd. No. R13 M L A MS m.p. ( C)
70 4-(CF3CH2NHC(=0)) S CH2 OCH2 471 (M+1)
71 4-(c-PrCH2NHC(=0)) S CH2 OCH2 443 (M+1) 88-92
137 4-(Et0C(=0)) S CH2 OCH2 418 (M+1) 74-78
248 5-(c-PrCH2NHC(=0)) 0 CH2 OCH2 427 (M+1)
257 5-(CF3CH2NHC(=0)) 0 CH2 OCH2 455 (M+1) 99-103
259 5-(c-PrCH2NHC(=0)) S CH2 OCH2 443 (M+1) 117-121
275 5-(CF3CH2NHC(=0)) S CH2 OCH2 471(M+1)
INDEX TABLE F
/ R2c
0
R13-0
s A
---- N CF3
L
A dash "¨" in the R13 column means no R13 substituent is present and the
remaining carbon valence is occupied by
a hydrogen atom. A dash "¨" in the L column means that L is a direct bond.
Unless otherwise indicated, the
configuration of substituents about the double bond in the above structure is
as shown in the structure.
Cmpd. MS
m.p.
No. R13 L A R2c
NMR (M+1) ( C)
53 Et0C(=0) CH2 0 CH3 *
54 Et0C(=0) CH2 0 CH2CH20Me *
55 Et0C(=0) CH2 0 CH2CH=CH2 *
56 Et0C(=0) CH2 0 CH2CCH *
57 Et0C(=0) CH2 0 CH(CH3)2 *
64 (Ex. 5) Et0C(=0) CH2 0 CH2CH3 *
58-59
65 Et0C(=0) CH2 0 CH2CH2CH3 *
89 t-Bu0C(=0) CH2 0 CH2CH3 *
106 CF3CH2NHC(=0) CH2 0 CH2CH3
109-113
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
197
Cmpd. MS
m.p.
No. R13 L A R2c
NMR (M+1) ( C)
107 I\ICCH2NHC(=0) CH2 0 CH2CH3
114-118
116 HOC(=0) CH2 0 CH2CH3 *
127-131
117 c-PrCH2NHC(=0) CH2 0 CH2CH3
106-110
118 i-PrNHC(=0) CH2 0 CH2CH3
114-118
132 Et0C(=0) (CH2)2 0 CH2CH3 *
138 Me0C(=0) CH2 0 CH2CH3
105-109
139 i-Pr0C(=0) CH2 0 CH2CH3 399
140 Et0C(=0) CH2 CH2 CH2CH3 *
145 Et0C(=0) CH2 0 CH2CH2OH *
151 CH2 0 CH2CH3 *
167 Et0C(=0) CH2 CH20 CH2CH3 *
180 Cl CH2 0 CH2CH3 *
182 CF3 CH2 0 CH2CH3 *
183 Br CH2 0 CH2CH3 *
185 CI-ICCH20C(=0) CH2 0 CH2CH3 69-
73
186 PhCH20C(=0) CH2 0 CH2CH3 63-
67
205 I\IC CH2 0 CH2CH3 *
216 MeC(=0)CH20C(=0) CH2 0 CH2CH3 64-
68
217 n-Pr0C(=0) CH2 0 CH2CH3 399
218 n-Bu0C(=0) CH2 0 CH2CH3 413
219 i-Bu0C(=0) CH2 0 CH2CH3 413
220 c-PrCH20C(=0) CH2 0 CH2CH3 411
221 CI(CH2)30C(=0) CH2 0 CH2CH3 433
222 Me0CH2CH20C(=0) CH2 0 CH2CH3 79-
83
242 CH2=C(Me)CH20C(=0) CH2 0 CH2CH3 411
243 CH3CCCH20C(=0) CH2 0 CH2CH3
105-109
244 PhC(=0)CH20C(=0) CH2 0 CH2CH3
114-118
245 I\ICCH2CH20C(=0) CH2 0 CH2CH3 * 81-
85
246 CH2=CHCH20C(=0) CH2 0 CH2CH3 397
267 Et0C(=0) CH(Me) 0 CH2CH3 *
294 Et0C(=0) (CH2)3 0 CH2CH3 * 413
298 Et0C(=0) CH2 0 CH2CF3 *
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
198
Cmpd. MS
m.p.
No. R13 L A R2c NMR (M+1) ( C)
316 Et0C(=0) 0 CH2CH3 371
328 HOC(=0) (CH2)2 0 CH2CH3 *
354 Me0C(=0) (CH2)2 0 CH2CH3 * 385
380 Et0C(=0) CH2 N(C1\1) CH2CH3
371
400 Et0C(=0) CH2 0 CH2CI\T 396
413 c-propyl-NHC(=0) CH2 0 CH2CH3 396
414 CH3NHC(=0) CH2 0 CH2CH3 370
422 Et0C(=0) CH2 0 S(=0)2CF3 489
427 Me0C(=0)CH2NHC(=0) CH2 0 CH2CH3 428
428 c-pentyl-NHC(=0) CH2 0 CH2CH3 424
435 2-pyrimidinyl-CH2NHC(=0) CH2 0 CH2CH3 448
436 CF2HCH2NHC(=0) CH2 0 CH2CH3 420
437 CH3CH2NHC(=0) CH2 0 CH2CH3 384
438 (CH3CH2)2NC(=0) CH2 0 CH2CH3 412
*See Index Table M for 19F NMR data.
INDEX TABLE Fl
R2c
0
Orl
R13 \ I CF3
\ N 5 H
L
6 (R8)q
Unless otherwise indicated, the configuration of substituents about the double
bond in the above structure is as shown
in the structure.
MS
Cmpd. No. R13 L (R8)q R2c NMR (M+1)
m.p. ( C)
262 Et0C(=0) CH2 3-F CH2CH3 *
344 Et0C(=0) CH2 3-Br CH2CH3 * 463 88-89
374 Et0C(=0) CH2 3-I CH2CH3 511
375 Et0C(=0) CH2 2-F CH2CH3 403
410 Et0C(=0) CH2 3-Me CH2CH3 399
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
199
MS
Cmpd. No. R13 L (R8)q R2c NMR (M+1)
m.p. ( C)
416 Et0C(=0) CH2 3-CI\T CH2CH3 410
430 Et0C(=0) CH2 2,3-di-F CH2CH3 421
458 Et0C(=0) CH2 3-C1 CH2CH3 419
464 Et0C(=0) CH2 2,3,5,6-tetrafluoro CH2CH3 457
*See Index Table M for 19F NMR data.
INDEX TABLE G
R2c
0
0
A
CF3 1 l'.
E R2d
L
A dash "¨" in the L column means that L is a direct bond. Unless otherwise
indicated, the configuration of
substituents about the double bond in the above structure is as shown in the
structure.
Cmpd. No. E L A R2d R2c NMR
MS
0
(Me)2N)\---11 -")_
58 ¨ 0 H CH2CH3 *
0
60 CH3S(=0)2 ¨ 0 H
CH2CH3 *
61 (Me)2N5(=0)2 ¨ 0 H
CH2CH3 *
62 CH3CH2S(=0)2 CH2 0 H
CH2CH3 *
72 HOC(=0) ¨ 0 H CH2CH3
* 275 (M-1)
73 i-Pr0C(=0) ¨ 0 H CH2CH3
* 318 (M+1)
74 CH2=CHCH20C(=0) ¨ 0 H CH2CH3
* 317 (M+1)
75 C1-1CCH20C(=0) ¨ 0 H CH2CH3
* 313 (M-1)
79 CH3C(=0) ¨ 0 H
CH2CH3 *
Et0
N
83 \r"--)-.------ \ CH2 0 H CH2CH3
* 401 (M+1)
0 N--
Ns /
N
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
200
Cmpd. No. E L A R2d R2c NMR MS
NN
\N--,
84 CH2 0 H CH2CH3 *
401 (M+1)
0
OEt
85 5-(CH30C(=0))-1H-imidazol-1-y1 CH2 0 H CH2CH3 *
371 (M+1)
86 4-(CH30C(=0))-1H-imidazol-1-y1 CH2 0 H CH2CH3 *
371 (M+1)
87 CH2 0 H CH2CH3 *
364 (M+1)
0
88 EtONCH2 0 H CH2CH3 *
364 (M+1)
N¨
N /
90 3-(Et0C(=0)-5-(Me0))-1H-pyrazol-1-y1 CH2 0 H CH2CH3 *
415 (M+1)
91 Me0 CH2 0 H CH2CH3 *
420 (M+1)
N
0
0
1\42t1(
92 Me CH2 0 H CH2CH3 *
360 (M+1)
N¨
o/
94 n-Pr0C(=0) ¨ 0 H CH2CH3 *
95 Et0C(=0) ¨ 0 H CH2CH3 *
305 (M+1)
96 Et0C(=0)CH=CHCH20 ¨ 0 H CH2CH3 *
99 NH2C(=0) ¨ 0 H CH2CH3 *
274 (M+1)
100 c-PrNHC(=0) ¨ 0 H CH2CH3 * 316 (M+1)
101 i-PrNHC(=0) ¨ 0 H CH2CH3 * 318 (M+1)
102 CliCCH2NHC(=0) ¨ 0 H CH2CH3 *
314 (M+1)
103 CH2=CHCH2NHC(=0) ¨ 0 H CH2CH3 *
316 (M+1)
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
201
Cmpd. No. E L A R2d R2c NMR MS
104 n-PrNHC(=0) ¨ 0 H CH2CH3 *
318 (M+1)
105 MeNHC(=0) ¨ 0 H CH2CH3 *
290 (M+1)
109 t-Bu0C(=0)NH CH2 0 H CH2CH3 261
(M+1)
110 NH2 CH2 0 H CH2CH3 262
(M+1)
111 Et0C(=0)NH CH2 0 H CH2CH3
*
113 CF3CH2C(=0)NH CH2 0 H CH2CH3
*
114 MeOCH(CH3)C(=0)NH CH2 0 H CH2CH3
*
0
119 Et0N CH2 0 H CH2CH3 *
386 (M+1)
------- \
N--
-..., /
N
Et0
0
120 CH2 0 H CH2CH3 *
386 (M+1)
----
N--
N.-zz... /
N
0
Et0
121 ---- N¨
CH2 0 H CH2CH3 * 386 (M+1)
N /
N
F3C
N
143 ) ¨ 0 H CH2CH3
*
0 ----
N
144 I\TC ¨ 0 H CH2CH3
*
148 HC(=0) ¨ 0 H CH2CH3
149 EtS(=0)2NH CH2 0 H CH2CH3
*
150 EtC(=0)NH CH2 0 H CH2CH3
*
152 3,5-di-Me-1H-pyrazol-1-y1 CH2 0 H CH2CH3 *
341 (M+1)
153 4-(Et0C(=0))-1H-imidazol-1-y1 CH2 0 H CH2CH3 *
385 (M+1)
154 I\TC CH2 0 H CH2CH3
*
155 I\TCS CH2 0 H CH2CH3
*
156 1H-imidazol-1-y1 CH2 0 H CH2CH3 *
313 (M+1)
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
202
Cmpd. No. E L A R2d R2c NMR MS
0
184 N¨ CH2 0 H CH2CH3
*
0
193 NH2C(=0)0 CH2 0 H CH2CH3
*
195 OH CH2 0 H CH2CH3
*
196 EtNHC(=0)0 CH2 0 H CH2CH3
*
210 i-PrC(=0)NH CH2 0 H CH2CH3 *
332 (M+1)
211 c-PrC(=0)NH CH2 0 H CH2CH3 331
(M+1)
0
224 CH2 0 H CH2CH3 *
330 (M+1)
N-
0
Mf.....\_
225 Me CH2 0 H CH2CH3 *
358 (M+1)
........ ../N-
0
0"--(
226 N¨
CH2 0 H CH2CH3 * 380 (M+1)
11110
230 Me0C(=0) ¨ 0 H CH2CH3 *
291 (M+1)
268 4-(Et0C(=0))-1-piperidinyl CH2 0 H CH2CH3 *
402 (M+1)
269 3-(Et0C(=0))-1-piperidinyl CH2 0 H CH2CH3 *
402 (M+1)
270 [Note
4-(Et0C(=0))-pyridin-1-y1 CH2 0 H CH2CH3
*
7]
271 [Note
3-(Et0C(=0))-pyridin-1-y1 CH2 0 H CH2CH3
*
7]
0
278 Et0"--- ¨ 0 H CH2CH3 *
N......o
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
203
Cmpd. No. E L A R2d R2c NMR MS
279 NO2 ¨ 0 H CH2CH3 *
0
287 EtO CH2 0 H CH2CH3
*
1\TO
0
(Me)2N)10_
288 CH2 0 H CH2CH3
*
297 4-(Et0C(=0))-1H-pyrazol-1-yl-CH20 CH2 0 H CH2CH3 *
412 (M-1)
oCH2CHF2
306 N /LN CH2 0 H CH2CH3
405 (M+1)
LL
S(=0)2Me
307 N )N CH2 0 H CH2CH3
403 (M+1)
SMe
308 NN CH2 0 H CH2CH3
371 (M+1)
LL
309 4-(Me0C(=0))-1-piperidinyl CH2 0 H CH2CH3 *
388 (M+1)
310 3-(Me0C(=0))-1-pyrrolidinyl CH2 0 H CH2CH3 *
374 (M+1)
311 4-(NC)-1-piperidiny1 CH2 0 H CH2CH3 *
355 (M+1)
312 4-(Me0)-1-piperidinyl CH2 0 H CH2CH3 *
360 (M+1)
OCH2CH2Si(Me)3
313 NN CH2 0 H CH2CH3
441 (M+1)
364 (Ex. 9) 4-(Et0C(=0))-1H-pyrazol-1-yl-CH20 ¨ 0 H
CH2CH3 401 (M+1)
371 c-PrC(=0)NH ¨ 0 H CH2CH3
316 (M+1)
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
204
Cmpd. No. E L A R2d R2c NMR MS
0
373 )----N-- ¨ 0 H CH2CH3
330 (M+1)
H3C
379 2-F-PhC(=0)0 ¨ 0 H CH2CH3
371 (M+1)
0
li
383 07--:-....-s--N ¨ 0 H CH2CH3
380 (M+1)
/
Et
0
412 >----N--- ¨ 0 H CH2CH3
359 (M+1)
Et NH
426 4-(2,4-di-F-PhNHC(=0))-1H-pyrazol-1-y1 ¨
0 CH2CH3 468 (M+1)
433 Me0 CH2 0 H
CH2CH3 *
434 C1CH2 ¨ 0 H CH2CH3 **
445 MeC(=0)S CH2 0 H
CH2CH3 *
461 2-F-PhC(=0)NH ¨ 0 H CH2CH3
370 (M+1)
*See Index Table M for 19F NMR data.
**See Index Table N for 1H NMR data.
Note 7: HBr salt.
INDEX TABLE H
/R2c
0
R13 /3"--------N 0 A CF3
==.,._ \
N
R2d
L
5
Unless otherwise indicated, the configuration of substituents about the double
bond in the above structure is
as shown in the structure.
Cmpd. No. R13 L A R2d R2c NMR
MS
158 3-CH3 CH2 0 H CH2CH3 * 371 (M+1)
181 3-CF3 CH2 0 H CH2CH3 * 379 (M-1)
231 3-(Et0C(=0)) CH2 0 H CH2CH3 *
241 5-(Et0C(=0)) CH2 0 H CH2CH3 *
250 5-(Me0C(=0)) CH2 0 H CH2CH3 * 371 (M+1)
251 3-(Me0C(=0)) CH2 0 H CH2CH3 * 371 (M+1)
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
205
Cmpd. No. R13 L A R2d R2c NMR
MS
252 5-(t-BuOC(=0)) CH2 0 H CH2CH3 * 411
(M-1)
253 3-(t-BuOC(=0)) CH2 0 H CH2CH3 * 411
(M-1)
291 3-(CH2=CHCH20C(=0)) CH2 0 H CH2CH3 * 397
(M+1)
292 3-(n-PrOC(=0)) CH2 0 H CH2CH3 * 399
(M+1)
293 3-(CH3CCCH20C(=0)) CH2 0 H CH2CH3 * 409
(M+1)
299 3-(HOC(=0)) CH2 0 H CH2CH3 *
325 3-(HCCCH20C(=0)) CH2 0 H CH2CH3 * 395
(M+1)
326 3-(CH3CH2CCCH20C(=0)) CH2 0 H CH2CH3 * 423
(M+1)
327 3-(i-PrOC(=0)) CH2 0 H CH2CH3 * 399
(M+1)
356 3-(n-BuOC(=0)) CH2 0 H CH2CH3 * 413
(M+1)
357 3-(i-Bu0C(=0)) CH2 0 H CH2CH3 * 413
(M+1)
358 3-(CH2=C(Me)CH20C(=0)) CH2 0 H CH2CH3 * 411
(M+1)
359 3-(CH3C(=0)CH20C(=0)) CH2 0 H CH2CH3 * 413
(M+1)
360 3-(Me0CH2CH20C(=0)) CH2 0 H CH2CH3 * 415
(M+1)
361 3-(c-BuCH20C(=0)) CH2 0 H CH2CH3
* 425 (M+1)
362 3-(C1CH2CH2CH20C(=0)) CH2 0 H CH2CH3 * 433
(M+1)
*See Index Table M for 19F NMR data.
INDEX TABLE I
/R2c
0
R13
/7-7=3 / 0 A
N CF3
R2d
L
A dash "¨" in the R13 column means no R13 substituent is present and the
remaining carbon valences are
5 occupied by hydrogen atoms. Unless otherwise indicated, the configuration
of substituents about the double bond in
the above structure is as shown in the structure
Cmpd. No. R13 L A R2d R2c NMR MS
81 5-CN CH2 0 H CH2CH3 * 337 (M-1)
82 3-CN CH2 0 H CH2CH3 * 337 (M-1)
122 5-(Me0C(=0)) CH2 0 H CH2CH3 * 370 (M-1)
123 3-(Me0C(=0)) CH2 0 H CH2CH3 * 370 (M-1)
157 CH2 0 H CH2CH3 * 312 (M-1)
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
206
Cmpd. No. R13 L A R2d R2c NMR MS
260 5-MeS CH2 0 H CH2CH3 * 358 (M-1)
261 3-MeS CH2 0 H CH2CH3 * 360 (M+1)
*See Index Table M for 19F NMR data.
INDEX TABLE J
R2c
0
4
R13) ---T CF3
2 10 A 12d
R
M L
Unless otherwise indicated, the configuration of substituents about the double
bond in the above structure is
5 as shown in the structure.
Cmpd. No. R13 M L A R2d R2c NMR
MS
129 4-(CF3CH2NHC(=0)) S CH2 0 H CH2CH3 *
130 4-(c-PrCH2NHC(=0)) S CH2 0 H CH2CH3 *
254 5-(c-PrCH2NHC(=0)) S CH2 0 H CH2CH3
427 (M+1)
255 5-(CHF2CH2NHC(=0)) 0 CH2 0 H CH2CH3
421 (M+1)
258 5-(c-PrCH2NHC(=0)) 0 CH2 0 H CH2CH3
411 (M+1)
276 5-(CHF2CH2NHC(=0)) S CH2 0 H CH2CH3
437 (M+1)
*See Index Table M for 19F NMR data.
INDEX TABLE K
R2c
0
L 01 0
R13--Ci CF3
---"N R2d
A dash "¨" in the L columna means that L is a direct bond. Unless otherwise
indicated, the configuration of
substituents about the double bond in the above structure is as shown in the
structure.
Cmpd. No. R13 L R2d R2c NMR MS
265 (Ex. 7) Et0C(=0) CH2 H CH2CH3
* 385 (M+1)
300 CH3CCCH20C(=0) CH2 H CH2CH3
* 409 (M+1)
304 Et0C(=0) CH(Me) H CH2CH3
399 (M+1)
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
207
Cmpd. No. R13 L R2d R2c NMR MS
317 Et0C(=0) H CH2CH3 371
(M+1)
323 HOC(=0) CH2 H CH2CH3 * 357
(M+1)
324 Et0C(=0) CH2 H n-Pr 399
(M+1)
330 Me0C(=0) CH2 H CH2CH3 * 371
(M+1)
331 n-PrOC(=0) CH2 H CH2CH3 * 399
(M+1)
332 i-PrOC(=0) CH2 H CH2CH3 * 399
(M+1)
333 CH2=CHCH20C(=0) CH2 H CH2CH3 * 397
(M+1)
334 i-BuOC(=0) CH2 H CH2CH3 * 413
(M+1)
335 CH2=C(Me)CH20C(=0) CH2 H CH2CH3 * 411
(M+1)
336 CliCCH20C(=0) CH2 H CH2CH3 * 395
(M+1)
337 CH3C(=0)CH20C(=0) CH2 H CH2CH3 * 413
(M+1)
338 C1(CH2)30C(=0) CH2 H CH2CH3 * 433
(M+1)
339 n-BuOC(=0) CH2 H CH2CH3 * 413
(M+1)
340 CH30(CH2)20C(=0) CH2 H CH2CH3 * 415
(M+1)
341 c-PrCH20C(=0) CH2 H CH2CH3 * 411
(M+1)
342 c-BuCH20C(=0) CH2 H CH2CH3 * 425
(M+1)
343 EtNHC(=0) CH2 H CH2CH3 * 382
(M-1)
345 Et0C(=0) CH2CH2 H CH2CH3 * 399
(M+1)
347 CHF2CH20C(=0) CH2 H CH2CH3 * 421
(M+1)
348 CF3CH2CH20C(=0) CH2 H CH2CH3 * 453
(M+1)
349 CF2=CFCH2CH20C(=0) CH2 H CH2CH3 * 465
(M+1)
350 (Me)2CH(CH2)20C(=0) CH2 H CH2CH3 *
351 CH30(CH2)30C(=0) CH2 H CH2CH3 * 429
(M+1)
352 CF30(CH2)20C(=0) CH2 H CH2CH3 * 469
(M+1)
355 CF3(CH2)30C(=0) CH2 H CH2CH3 * 467
(M+1)
365 Et0C(=0) CH2 H CH3 *
390 c-pentyl-NHC(=0) CH2 H CH2CH3 424
(M+1)
391 c-propyl-NHC(=0) CH2 H CH2CH3 396
(M+1)
393 c-propyl-CH2NHC(=0) CH2 H CH2CH3 410
(M+1)
394 CF2HCH2NHC(=0) CH2 H CH2CH3 420
(M+1)
401 CF3CH2NHC(=0) CH2 H CH2CH3 438
(M+1)
402 2-pyrimidinyl-CH2NHC(=0) CH2 H CH2CH3 448
(M+1)
403 CH3NHC(=0) CH2 H CH2CH3 370
(M+1)
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
208
Cmpd. No. R13 L R2d R2c NMR MS
404 (CH3CH2)2NC(=0) CH2 H CH2CH3 412
(M+1)
415 i-PrNHC(=0) CH2 H CH2CH3 398
(M+1)
421 Et0C(=0) (CH2)3 H CH2CH3 413
(M+1)
*See Index Table M for 19F NMR data.
INDEX TABLE K1
R2c
0
R1 3
L
N. 654 ,
C F3
4 1
H
3
R8 5
A dash "¨" in the R8 column means no R8 substituent is present and the
remaining carbon valence is occupied
by a hydrogen atom. Unless otherwise indicated, the configuration of
substituents about the double bond in the above
structure is as shown in the structure.
Cmpd. No. R13 L R8 R2c MS
301 4-(Et0C(=0)) CH2 2-F CH2CH3
403 (M+1)
302 4-(Et0C(=0)) CH2 6-F CH2CH3
403 (M+1)
303 4-(Et0C(=0)) CH2 2-Me CH2CH3
399 (M+1)
378 3-(Et0C(=0)) CH2 5-Me0 CH2CH3
415 (M+1)
405 3-(Et0C(=0)) CH2 5-Me CH2CH3
399 (M+1)
406 4-(Et0C(=0)) CH2 5-Me CH2CH3
399 (M+1)
407 3-(Et0C(=0)) CH2 4-Me0 CH2CH3
415 (M+1)
408 4-(Et0C(=0)) CH2 4-Me0 CH2CH3
415 (M+1)
418 4-(Et0C(=0)) CH2 4-F CH2CH3
403 (M+1)
419 5-(Et0C(=0)) CH2 4-F CH2CH3
403 (M+1)
420 3-(Et0C(=0)) CH2 4-F CH2CH3
403 (M+1)
448 5-(Et0C(=0)) CH2 CH2CH3
386 (M+1)
449 3-(Et0C(=0)) CH2 CH2CH3
386 (M+1)
451 4-(Et0C(=0)) CH2 6-Me CH2CH3
399 (M+1)
462 5-(Et0C(=0)) CH2 5-Me CH2CH3
399 (M+1)
463 5-(Et0C(=0)) CH2 4-Me0 CH2CH3
415 (M+1)
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
209
INDEX TABLE L
m.p.
Cmpd. No. Structure NMR MS (
C)
OEt
0
Et0
63 [Note 6] ) a
0 CF3 *
CH3
0
I--\
0 0
124 Et0)eN
N0><CF3 (M+1)
402
\ It
0
0/
401
146 *
(M+1)
101 CF3
Et0
07)
147
N
*
0\---0 274
1101 CF3
(M+1)
0
165
02N 1,
1W CF3
0 *
I--\
402
168 Et0
0
I CF3
(M+1)
) \ N,
0
F /--\
0 0
263 Et0 0><
) 01
*I CF3 *
0
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
210
m.p.
Cmpd. No. Structure NMR MS (
C)
HO OH
0
40 0)(
266 (Ex. 6)
>----01 CF3 *
Et0 ----N
/1\TI\IN/S
273 0-C/ ________ 0\
\ ** )0)
Et0
F3C
0
OH
0)11
305 0 0 CF3 *
e
320 Et0
HO OH 391
OT 0)( (M+1)
(1)
N / .CF3
___...(
Et0
OEt
321 *
ON 0
CF3
eEt0
HO OH 389
346 *
ON (M+1)
1\1 40 0)(
CF3
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
211
m.p.
Cmpd. No. Structure NMR MS (
C)
_____O
Et0
r¨\
353 0 z0 *
M+1)
O 417
N (
I\I 0 (i)CF3
.40
Et0 OEt
40 O.,1 *
367
).---"N CF3
N\
OH
.....i.-OH
0 ___________________ CNN 349
F3 (M+1)
81-84
368
,,C
¨N
N
Et0
OEt
0 > 403
370 CF3
(M+1)
Et0
OEt
455
377 CF3
(M+1)
F3C II
Me0 OSiMe3
385 Br---.C111 CF3 *
'N
HO OH
40 0)( 386 Br-----C\T CF3 *
83.7-
86.5
'N
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
212
m.p.
Cmpd. No. Structure NMR MS (
C)
F /--\
0 0
Et0 F I. 0><
CF3 473
392 59-
62
) __ Cli\T (M+1)
0 F
F
Me0 OSiMe3
0><
395 ---,N CF3 *
Br ____________________ C I
\ N
OEt
437
398 CF3
(M+1)
F2HC N __
H
...._<0
Et0 CF3
(M+1)
385
399 / 40Et
ON
N
HO OH
0 0)( 403
417
, _____________________ 0 c,3
(m+1)
-----N
Et0
HO OH
O 0)(
423 CI CF3 *
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
213
m.p.
Cmpd. No. Structure NMR MS (
C)
HO OH
F 0><
CF3
409
424
0
(M+1)
0
OEt
OEt
F
CF3
419
425 (M+1)
0
OEt
HO OH
0><289
439 CF3
(M-1)
F3C
CF3
HO OH
0>< 339
440 CF3
(M-1)
F3C
HO OH
0><
2
CF3 72
441
(M-1)
F3C/,
0 0
279
442
0><
CF3
(M-1)
H3C
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
214
m.p.
Cmpd. No. Structure NMR MS (
C)
OEt
0 40 0,1
446 ) _____ 0 CF3 *
Et0 N
1:Ni
Et0 OEt
447 40 0,1
*
CF3
N:::::-*"
OEt
O.,1 373
450 ) T CF3
(M+1)
Me0 N')
HO OH
Et0
0
452 )(
)---C11 CF3 369
0 (M-1)
'N
H3C
q OEt
453 \ / N 40 01
CF3
365
I (M+1)
----"N
F OEt
0,1
CF3
1\I o 01 419
454
____F (M+1)
Et0
0
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
215
m.p.
Cmpd. No. Structure NMR MS (
C)
OEt
CF3
417
457 s
(M+1)
Et0
0
0 OEt
460 HO
CF3 275
(M-1)
Note 6: 3:2 mixture of geometric isomers.
*See Index Table M for 19F NMR data.
**See Index Table N for 1H NMR data.
INDEX TABLE M
Cmpd. Cmpd.
No. 19F NMR Dataa No. 19F NMR Dataa
1 6-84.92 (s). 177 6-84.85 (s).
2 6 (DMSO-d6) -81.80 (s). 179 6-62.79 (s), -81.40 (s).
3 6-81.39 (s). 180 6 -70.10 (s).
4 6 (DMSO-d6) -81.50 (s). 181 6-61.85 (s).
6 -82.61 (s), -75.48 (s). 182 6-56.40 (s).
6 6-79.03 (s). 183 6 -70.09 (s).
7 6-81.50 (s), -81.71 (s). 184 6-70.11 (s).
8 6 -81.50 (s), -81.71 (s). 189 6 -81.42 (s).
9 6-81.27 (s). 190 6-81.38 (s).
6 -79.64 (s). 191 6 -81.42 (s).
12 6-81.01 (s). 192 6-81.39 (s).
13 6-81.38 (s). 193 6-70.01 (s).
14 6-81.39 (s). 195 6-70.04 (s).
6-81.38 (s). 196 6-70.08 (s)..
16 6-81.39 (s). 197 6-72.38 (s), -81.38 (s).
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
216
Cmpd. Cmpd.
No. 1-9F NMR Dataa No. 1-9F NMR Dataa
17 6-81.38 (s). 198 -- 6-81.38 (s).
18 6-81.38 (s). 199 6-81.38 (s).
20 6-78.49 (s). 200 6-81.38 (s).
21 6-80.99 (s). 201 -- 6-81.38 (s).
22 6 -81.39 (s). 202 -- 6 -81.39 (s).
23 6-81.37 (s). 203 -- 6-81.39 (s).
24 6-81.37 (s). 204 6-81.38 (s).
25 6-81.37 (s). 205 -- 6-70.14 (s).
26 6-81.39 (s). 206 6-84.95 (s).
27 6-81.41 (s). 209 6-81.36 (s).
28 6-81.38 (s). 210 6-70.08 (s).
29 6-84.92 (s). 214 -- 6-81.43 (s).
31 6 (DMSO-d6) -81.91 (s). -- 224 -- 6-70.09
(s).
32 6-81.39 (s). 225 6-70.08 (s).
33 6 (DMSO-d6) -81.83 (s). -- 226 -- 6-70.10
(s).
34 6 (DMSO-d6) -81.89 (s). 227 6-81.57
(s), -84.95 (s).
35 6-84.94 (s). 228 6-81.39 (s).
36 6 (DMSO-d6) -81.37 (s). 230 6 -70.21
(s).
37 6 (DMSO-d6) -81.82 (s). 231 6-70.12
(s).
39 6-84.93 (s). 232 -- 6-81.39 (s).
40 6 (acetone-d6) -83.12 (s). -- 233 -- 6 -
84.87 (s).
41 6-84.81 (s). 234 6-84.95 (s).
42 6 (DMSO-d6) -81.82 (s). 235 6-81.45
(s).
43 6 (DMSO-d6) -81.82 (s). 236 6-81.46
(s).
44 6-84.21 (s). 237 6 -81.44 (s).
45 6 (DMSO-d6) -81.82 (s), -72.33 (t). 239 6 -81.42 (s).
6 (DMSO-d6) -81.83 (s), -82.96 (s),
46 240 6 -81.39 (s)
-122.29 (t).
47 6 (DMSO-d6) -81.82 (s). 241 6-70.11 (s).
48 6 (DMSO-d6) -81.82 (s). 245 6-68.61 (s).
49 6 (DMSO-d6) -81.82 (s). 249 6-81.39 (s).
6 (DMSO-d6) -81.82 (s), -138.53 (m),
50 250 6-70.11 (s).
-139.66 (m).
51 6-87.93 (s). 251 6-70.13 (s).
52 6 -76.89 (s). 252 6 -70.09 (s).
53 6-70.09 (s). 253 6 -70.11(s).
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
217
Cmpd. Cmpd.
No. 1-9F NMR Dataa No. 1-9F NMR Dataa
54 6 -69.99 (s). 260 6 -70.12 (s).
55 6-69.95 (s). 261 6-70.12 (s).
56 6-69.73 (s). 262 6 -70.33 (s).
57 6-69.75 (s). 263 6 -81.60 (s), -132.13
(s).
58 6 -70.10 (s). 264 6 -84.92 (s).
60 6-70.30 (s). 265 6 -70.09 (s).
61 6 -70.26 (s). 266 6-84.88 (s).
62 6-70.15 (s). 267 6-70.13 (s).
63 6-63.30 (s), -63.67 (s). 268 6-
70.03 (s).
64 6-70.13 (s). 269 6-70.03 (s).
65 6-70.03 (s). 270 6-70.12 (s).
66 6 -85.74 (s). 271 6 -70.12 (s).
67 6 -82.36 (s). 272 6 -69.99 (s).
72 6 -70.24 (s). 278 6-70.11 (s).
73 6 -70.20 (s). 279 6-70.31 (s).
74 6 -70.22 (s). 280 6 -84.80 (s).
75 6-70.22 (s). 284 6-81.38 (s).
79 6 -70.22 (s). 285 6 -81.39 (s).
80 6 -84.87 (s). 286 6 -84.94 (s).
81 6-70.17 (s). 287 6-70.05 (s).
82 6 -70.14 (s). 288 6 -70.04 (s).
83 6-70.17 (s). 289 6-81.39 (s).
84 6-70.16 (s). 290 6-81.37 (s).
85 6 -70.14 (s). 291 6 -70.12 (s).
86 6-70.12 (s). 292 6-70.13 (s).
87 6-70.11 (s). 293 6-70.13 (s).
88 6 -70.19 (s). 294 6-70.01 (s).
89 6-70.13 (s). 296 6-81.38 (s).
90 6-70.16 (s). 297 6 -70.01 (s).
91 6-70.12 (s). 298 6-70.05 (s), -74.96 (s).
92 6-70.13 (s). 299 6-70.12 (s).
93 6 -81.42 (s). 300 6 -70.10 (s).
94 6 -70.21 (s). 305 6 -84.85 (s).
95 6 -70.21 (s). 309 6 -70.02 (s).
96 6 -69.98 (s). 310 6-70.04 (s).
97 6 -84.95 (s). 311 6-70.01 (s).
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
218
Cmpd. Cmpd.
No. 1-9F NMR Dataa No. 1-9F NMR Dataa
98 6-81.40 (s). 312 6-70.03 (s).
99 6-70.19 (s). 318 6-81.38 (s).
100 6-70.16 (s). 319 6-79.29 (s), 82.67 (s).
101 6-70.15 (s). 321 6-68.60 (s).
102 6-70.18 (s). 322 6-81.70 (s).
103 6-70.16 (s). 323 6-70.10 (s).
104 6-70.16 (s). 325 6-70.11 (s).
105 6-70.16 (s). 326 6-70.13 (s).
111 6-70.08 (s). 327 6-70.13 (s).
112 6-81.43 (s). 328 6-68.54 (s).
113 6 -63.01 (s), -70.10 (s). 329 6-77.08 (s).
114 6-70.09 (s). 330 6-70.09 (s).
116 6-70.14 (s). 331 6-70.10 (s).
119 6-70.16 (s). 332 6-70.08 (s).
120 6-70.15 (s). 333 6-70.09 (s).
121 6-70.16 (s). 334 6-70.09 (s).
122 6 -70.14 (s). 335 6 -70.09 (s).
123 6-70.15 (s). 336 6-70.08 (s).
126 6-81.38 (s). 337 6-70.08 (s).
127 6-81.38 (s). 338 6-70.06 (s).
129 6-70.06 (s), -72.25 (s). 339 6 -70.10
(s).
130 6 70.06 (s). 340 6-70.09 (s).
131 6-84.93 (s). 341 6-70.09 (s).
132 6-70.05 (s). 342 6-70.11 (s).
133 6-81.40 (s). 343 6-70.11 (s).
134 6-81.40 (s), -73.70 (s). 344 6-
70.50 (s).
140 6-69.16 (s). 345 6-68.59 (s).
164 6-81.33 (s). 346 6-81.82 (s).
165 6-81.34 (s). 347 6-70.09 (s), -
125.54 (s).
166 6-81.38 (s). 348 6-64.93 (s), -
70.09 (s).
6-70.13 (s), -103.21 (s),
167 6-69.60 (s). 349
-123.98 (s), -175.15 (s).
141 6-81.28 (s). 350 6-70.09 (s).
142 6-84.83 (s). 351 6-70.09 (s).
143 6- 60.46(s), -70.25 (s). 352 6-
60.95 (s), -70.12 (s).
144 6 -70.30 (s). 353 6 -81.41 (s).
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
219
Cmpd. Cmpd.
No. 19F NMR Dataa No. 19F NMR Dataa
145 6 -69.79 (s). 354 6 -70.03 (s).
146 6-81.37 (s). 355 6-66.44 (s), -70.09 (s).
147 6-81.36 (s). 356 6-70.14 (s).
149 6-70.07 (s). 357 6-70.13 (s).
150 6-70.07 (s). 358 6-70.12 (s).
151 6-70.09 (s). 359 6-70.11 (s).
152 6 -70.09 (s). 360 6 -70.12 (s).
153 6-70.12 (s). 361 6-70.13 (s).
154 6 -70.10 (s). 362 6-70.11 (s).
155 6 -70.05 (s). 365 6 -70.05 (s).
156 6 -70.05 (s). 367 6 -70.08 (s).
157 6-70.19 (s). 369 6-83.07 (s).
158 6-70.10 (s). 385 6-80.30 (s).
160 6-81.44 (s). 386 6-84.80 (s).
161 6-81.38 (s). 395 6-80.30 (s).
162 6 (DMSO-d6) -80.02 (s). 396 6 -84.90 (s).
163 6-81.38 (s). 423 6-84.80 (s).
169 6-81.38 (s). 432 6-84.80 (s).
170 6-81.38 (s). 433 6-70.00 (s).
171 6-81.37 (s). 443 6 -81.72 (s).
172 6-81.37 (s). 445 6-70.10 (s).
174 6 -80.00 (s). 446 6 -70.10 (s).
176 6-81.40 (s). 447 6-70.08 (s).
a 19F NMR spectra are reported in ppm relative to CF3CC13, in CDC13 solution
unless indicated otherwise.
Couplings are designated by (s)-singlet, (t)-triplet and (m)-multiplet.
INDEX TABLE N
Compound
1H NMR Dataa
No.
273 (CDC13): 6 1.36-1.32 (t, 3H), 4.21 (s, 6H), 4.32-4.25 (q, 2H),
5.32 (s, 2H), 6.20 (s, 1H),
6.70 (s, 1H), 7.89 (s, 1H), 7.95 (s, 1H).
366 (DMSO-d6): 6 1.26 (t, 3H), 3.98 (s, 2H), 4.21 (q, 2H), 6.03 (s,
2H), 6.86-6.94 (m, 2H),
6.95-7.06 (m, 2H), 7.27 (s, 2H), 7.94 (s, 1H), 8.53 (s, 1H).
434 (CDC13): 6 1.34 (t, 3H), 4.18 (s, 2H), 4.57 (q, 2H), 6.78 (s,
1H), 7.05 (s, 2H), 7.36 (s, 2H).
a 1H NMR data are reported in ppm downfield from tetramethylsilane. Couplings
are designated by (s)-singlet,
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
220
(t)-triplet, (q)-quartet.
BIOLOGICAL EXAMPLES OF THE INVENTION
General protocol for preparing test suspensions for Tests A-E: the test
compounds were first
dissolved in acetone in an amount equal to 3% of the final volume and then
suspended at the
desired concentration (in ppm) in acetone and purified water (50/50 mix by
volume) containing
250 ppm of the surfactant PEG400 (polyhydric alcohol esters). The resulting
test suspensions
were then used in Tests A-E.
TEST A
The test solution was sprayed to the point of run-off on soybean seedlings.
The following
day the seedlings were inoculated with a spore suspension of Phakopsora
pachyrhizi (the causal
agent of Asian soybean rust) and incubated in a saturated atmosphere at 22 C
for 24 h, and then
moved to a growth chamber at 22 C for 8 days, after which time visual disease
ratings were made.
TEST B
The test solution was sprayed to the point of run-off on wheat seedlings. The
following day
the seedlings were inoculated with a spore suspension of Puccinia recondita f.
sp. tritici (the
causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20
C for 24 h, and
then moved to a growth chamber at 20 C for 6 days, after which time disease
ratings were made.
TEST C
The test solution was sprayed to the point of run-off on grape seedlings. The
following day
the seedlings were inoculated with a spore suspension of Uncinula necator (the
causal agent of
grape powdery mildew) and incubated in a growth chamber at 20 C for 12 days,
after which time
disease ratings were made.
TEST D
The test solution was sprayed to the point of run-off on wheat seedlings. The
following day
the seedlings were inoculated with a spore suspension of Zyrnoseptoria tritici
(the causal agent of
wheat leaf blotch) and incubated in a saturated atmosphere at 24 C for 48 h,
and then moved to
a growth chamber at 20 C for 17 days, after which time disease ratings were
made.
TEST E
The test suspension was sprayed to the point of run-off on wheat seedlings.
The following
day the seedlings were inoculated with a spore dust of Blurneria grarninis f.
sp. tritici, (also known
as Erysiphe grarninis f. sp. tritici, the causal agent of wheat powdery
mildew) and incubated in a
growth chamber at 20 C for 8 days, after which time visual disease ratings
were made.
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
221
Results for Tests A-E are given in Table A. In the Table, a rating of 100
indicates 100%
disease control and a rating of 0 indicates no disease control (relative to
the controls). An asterisk
or a double asterisk "**" or a triple asterisk "***" next to the rating value
indicates a 50 ppm,
ppm and 250 ppm test suspension was used, respectively. A dash (¨) indicates
the compound
5 was not tested.
TABLE A
Cmpd. No. Rate in ppm Test A Test B Test C Test D
Test E
1 250 100 91 97 81
2 10 77 32
3 10 100 0
4 10 100 89 100*
5 10 0 0
6 10 0 0
7 10 94 0
8 10 96 9
9 10 98 86
10 10 100 86
12 10 13 0
13 10 99 0
14 10 100 0
10 100 0
16 10 99 0
17 10 100 0
18 10 100 0
10 98 86
21 10 84 23
22 10 38 0
23 10 0 19
24 10 81 91
10 0 0
26 10 99 0
27 10 0 0
28 10 0 0
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
222
Cmpd. No. Rate in ppm Test A Test B Test C Test D Test
E
29 10 84 28 0*** 79***
30 10 0 0
31 10 44 93
32 50 100 68 100** 89*** 97***
33 10 96 86
34 10 0 80
35 10 99 32
36 10 70 0
37 10 99 86
38 10 97 89
39 10 91 79
40 10 91 68
41 10 92 23
42 10 99 85
43 10 96 60
44 10 97 85 16*** 98*** 91***
45 10 87 85
46 10 64 85
47 50 100 95
48 50 100 91
49 10 0 86
50 10 54 91
51 10 0 0 81*** 3*** 0***
52 10 99 0
53 50 100 67
54 10 0 0
55 10 0 0
56 10 38 0
57 250 100 0 64*** 28 95***
58 10 0 0
60 10 0 0
61 10 0 0
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
223
Cmpd. No. Rate in ppm Test A Test B Test C Test D
Test E
62 10 0 0
63 10 0 0
64 250 100 99 100** 73 99
65 10 100 0
66 50 92 89
67 50 65 0
68 10 100 95
69 10 98 96
70 250 100 100 86 91 83
71 10 100 96
72 50 13 0
73 10 0 0
74 10 0 0
75 10 0 0
76 10 0 0
77 10 99 0
78 10 94 0
79 50 0 0
80 50 99 100 0 96*** 99***
81 10 0 0
82 10 97 0
83 10 82 0
84 10 0 0
85 10 89 0
86 10 99 0
87 10 0 0
88 10 65 0
89 10 0 0
90 10 100 0
91 10 0 0
92 10 0 0
93 10 96 0
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
224
Cmpd. No. Rate in ppm Test A Test B Test C
Test D Test E
94 10 0 0
95 10 0 0
96 10 13 0
97 50 94 0
98 250 100 100 31 77 0
99 10 0 80
100 10 0 0
101 10 0 0
102 10 0 0
103 10 0 0
104 10 0 80
105 10 0 68
106 10 0 0
107 10 0 0
109 10 0 0
110 50 79 0
111 10 0 0
112 10 0 0
113 10 0 0
114 50 44 0
115 250 0 0 58 19 56
116 10 100 0
117 10 23 0
118 50 100 0 77*** 13*** 76***
119 10 97 0
120 50 100 0 23 17 98
121 10 100 0
122 10 0 0
123 10 98 0
124 50 100 0 100 92*** 98
125 10 100 0
126 10 100 0 100*
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
225
Cmpd. No. Rate in ppm Test A Test B Test C
Test D Test E
127 10 100 0 100*
129 10 100 0
130 10 100 0
131 50 99 86
132 10 100 0 98*
133 10 79 0
134 10 89 32
135 10 86 61
136 10 98 83
137 10 79 0
138 10 100 0 100* 31*** 99***
139 10 100 0
140 10 98 23
141 10 0 0
142 10 92 100 19*** 100*** 99***
143 10 0 0
144 10 78 0
145 10 82 0
146 50 60 0
147 50 77 0
148 10 0 0
149 10 0 0
150 10 33 0
151 10 0 0
152 10 0 0
153 10 100 0
154 10 0 0
155 10 0 0
156 10 0 0
157 10 0 9
158 10 0 0
160 10 13 0
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
226
Cmpd. No. Rate in ppm Test A Test B Test C Test
D Test E
161 10 100 0
162 10 100 0 100*
163 10 100 0 100*
164 10 31 0
165 10 0 0
166 10 100 95
167 10 38 0
168 10 0 0
169 10 100 0
170 10 100 0 100*
171 10 100 0 99*
172 10 100 0
173 10 0 0
174 10 0 0
175 10 0 0
176 10 0 0
177 50 100 89
178 10 0 0
179 10 0 0
180 10 0 0
181 10 0 0
182 10 0 0
183 10 0 0 70*** 66*** 0***
184 10 0 0
185 10 100 0 100* 0*** 95***
186 10 100 0 100* 9*** 84***
187 10 93 74
188 10 100 0
189 10 0 0
190 10 0 0
191 10 0 0
192 10 0 0
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
227
Cmpd. No. Rate in ppm Test A Test B Test C Test D
Test E
193 10 0 86
195 10 0 0
196 10 0 74
197 10 0 0
198 10 0 0
199 10 100 0
200 10 100 0
201 10 100 0
202 10 100 0
203 10 50 0
204 10 100 0
205 10 0 0
206 50 100 98 34*** 93*** 93***
207 10 0 0
209 10 89 0
210 10 0 0
211 10 0 0
212 10 44 0
214 10 0 0
215 10 80 55
216 10 100 0 20*** 37*** 87***
217 10 100 0 75*** 23*** 96***
218 10 100 0 75*** 53*** 90***
219 10 100 0 92*** 0*** 83***
220 10 100 0 85*** 28*** 92***
221 10 100 0 41*** 10*** 95***
222 10 100 0 38*** 17*** 90***
223 10 75 0
224 10 0 0
225 10 0 0
226 10 0 0
227 10 99 55
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
228
Cmpd. No. Rate in ppm Test A Test B Test C Test D Test
E
228 10 100 0
229 50 99 100 96*** 99***
230 10 0 0
231 10 100 0
232 10 98 0
233 50 100 96
234 50 100 92
235 10 97 0
236 10 75 0
237 10 97 0
238 10 73 0
239 10 0 0
240 10 99 0
241 10 0 0
242 10 100 0 87*** 27*** 69***
243 10 100 0 29*** 0*** 56***
244 10 100 0 0*** 0***
245 10 100 0 24*** 18*** 76***
246 10 100 0 85*** 12*** 90***
247 10 13 0 21*** 79*** 21***
248 10 71 0 62*** 93*** 89***
249 10 100 0
250 10 0 0
251 10 100 9
252 10 0 0
253 10 0 0
254 10 73 0 10*** 67*** 56***
255 10 89 0 93*** 60*** 64***
256 10 73 0 15*** 95*** 82***
257 10 54 0 81*** 35*** 92***
258 10 96 0 64*** 13*** 53***
259 10 25 0 31*** 88*** 83***
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
229
Cmpd. No. Rate in ppm Test A Test B Test C Test D
Test E
260 10 0 0
261 10 0 0
262 10 100 0 99*
263 10 100 0 100*
264 10 99 80 95*** 96***
265 50 100 0 98
266 50 86 74
267 10 94 0
268 10 99 0
269 10 100 0
270 10 25 0
271 10 0 0
272 10 100 0
273 50 100 0 49*** 20*** 65***
274 10 48 0
275 10 0 0
276 10 13 0 100* 53*** 86***
277 10 50 45
278 50 94 0
279 50 0 0
280 50 100 100 99*** 99***
281 50 95 98
282 50 0 0
283 50 100 99
284 10 100 0
285 10 100 0
286 10 87 55
287 50 77 0
288 50 96 0
289 10 0 0
290 50 50 19
291 10 100 0
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
230
Cmpd. No. Rate in ppm Test A Test B Test C
Test D Test E
292 10 100 0
293 10 100 0
294 10 100 0
295 50 99 80
296 10 0 0
297 10 100 0
298 10 0 0
299 10 100 0
300 10 100 0
301 50 100 0 100*
302 50 99 0
303 50 0 0
304 50 96 0
305 10 70 0
306 50 96 68
307 50 0 0
308 50 25 0
309 10 100 0
310 10 100 0
311 10 0 0
312 10 0 0
313 50 0 0
314 50 0 0
316 50 100 9 100 2 73
317 50 0 0
318 10 100 0
319 50 100 41
320 10 89 68 81*** 91***
321 10 100 0
322 10 99 86 48*** 100*** 97***
323 50 100 0
324 10 0 0
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
231
Cmpd. No. Rate in ppm Test A Test B Test C Test D .. Test
E
325 10 100 0
326 10 100 0
327 10 100 0
328 10 100 0
329 50 100 41
330 10 100 0
331 10 100 0
332 10 100 0
333 10 100 0
334 10 100 0
335 10 100 0
336 10 100 0
337 10 100 0
338 10 100 0
339 10 100 0
340 10 100 0
341 10 100 0
342 10 100 0
343 10 0 0
344 50 100 0
345 10 0 0
346 10 0 0
347 50 100 0
348 10 100 0
349 10 100 0
350 10 100 0
351 10 100 0
352 10 100 0
353 50 0 0
354 10 100 0
355 10 100 0
356 10 100 0
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
232
Cmpd. No. Rate in ppm Test A Test B Test C Test D Test
E
357 10 100 9
358 10 100 0
359 10 100 0
360 10 100 0
361 10 100 0
362 10 100 0
364 50 100 0 100 0 56
365 10 100 0
366 10 79 55
367 10 0 0
368 50 0 0 33*** 0*** 0***
369
370 10 0 0
371 50 0 77
372 50 97 28 99*** 99***
373 50 81 0 56*** 99*** 98***
374 50 0 0 0*** 76***
375 50 100 0 66*** 95*** 99***
376 50 100 92 36 98*** 99***
377 10 44 0
378 10 0 0
379 50 0 0 93*** 0*** 21***
380 10 0 0 0*** 56***
381 10 25 28 0*** 69***
382 50 0 0 22*** 4*** 56***
383 50 0 0 74*** 0*** 0***
384 50 99 83 48*** 87***
385 50 100 68
386 10 84 19
387
388
389
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
233
Cmpd. No. Rate in ppm Test A Test B Test C Test D Test
E
390 50 0
391 50 0
392 10 97 19
393 50 38 0 63*** 69*** 0***
394 50 0 0 75*** 24*** 0***
395 50 100 100 100
396 50 31 19
398 10 0 0
399 50 97 0
400 50 100 0
401 10 0 0 35*** 0*** 0***
402 50 97 48*** 5*** 0***
403 50 54 74*** 17*** 0***
404 50 0 0 44*** 11*** 0***
405 50 0 0
406 50 0 0
407 50 0 0
408 50 44 0
409
410 10 100 0 88*** 11*** 13***
411 50 87 0
412 50 100 0
413 10 0 0 61*** 90*** 35***
414 10 45 0 91*** 97*** 90***
415 10 0 0 9*** 0*** 0***
416 50 81 0 34*** 0*** 0***
417 10 0 0
418 10 0 0
419 10 0 0
420 10 0 0
421 10 0 0
422 50 100 84
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
234
Cmpd. No. Rate in ppm Test A Test B Test C Test D Test
E
423 50 87 80
424 10 97 41
425 10 100 0
426 10 0 0 45*** 2*** 43***
427 10 13 0 5*** 53*** 29***
428 10 0 0 43*** 2*** 0***
430 50 100 0 82*** 3*** 99***
431 250 36 93 96
432 50 100 98
433 50 0 0
434 50 0 0
435 50 96 0 45*** 5*** 81***
436 50 99 0 48*** 0***
437 50 77 0 77*** 78*** 69***
438 50 73 0 59*** 26*** 98***
439
440
441
442 50 0 0
443 50 48 0
444
445 50 38 0
446 10 98 0
447 10 0 0
448 10 0 0
449 50 99 0
450 50 97 0
451 50 0 0
452
453 10 0 0
454 10 100 0 100
455 50 99 86 34 43 0
CA 03174932 2022-09-08
WO 2021/183707
PCT/US2021/021806
235
Cmpd. No. Rate in ppm Test A Test B Test C Test D Test E
456 50 99 93 6 80 98***
457 250 89** 0** 73 7 0
458 10 100 0 25*** 41*** 94***
459 50 100 97 37*** 0***
460
461 50 0 0 53*** 69***
462 10 0 0
463 10 0 0
464 50 100 0 73*** 4*** 99***
465 50 100 100 73*** 59*** 91***
The test results presented above in Table A for compounds of Formula 1
illustrate the
fungicidal activity of component (a) contributing to the plant disease control
utility of
compositions comprising component (a) in combination with component (b) and
optionally at
least one additional fungicidal compound according to the present invention.
TEST F below demonstrates the control efficacy of compositions of this
invention on Asian
soybean rust. The general protocol for preparing test compositions for Test F
was as follows:
Compound 32, Compound 64, azoxystrobin, benzovindiflupyr, bixafen,
chlorothalonil,
cyproconazole, epoxiconazole, fenpropidin, fenpropimorph, fluindapyr,
flutriafol, fluxapyroxad,
metominostrobin, picoxystrobin, prothioconazole, pydiflumetofen,
pyraclostrobin, tebuconazole
and trifloxystrobin were obtained as unformulated, technical-grade materials.
Copper hydroxide
and mancozeb was obtained as a formulated product marketed under the
trademarks KOCIDE
3000 and MANZATE, respectively. Unformulated materials were first dissolved in
acetone and
then suspended at the desired concentration (in ppm) in acetone and purified
water (50/50 mix by
volume) containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol
esters).
Formulated materials were dispersed in sufficient water to give the desired
concentration, and
neither organic solvent nor surfactant was added to the suspension. The
resulting test mixtures
were then used in Test F. The tests were run on four individual plants and the
results reported as
the mean average of the four plants.
The presence of a synergistic effect between two active ingredients was
established with the
aid of the Colby equation (see Colby, S. R. "Calculating Synergistic and
Antagonistic Responses
of Herbicide Combinations", Weeds, (1967), 15, 20-22):
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
236
p = A + B ¨ x B
100
=
Using the method of Colby, the presence of a synergistic interaction between
two active
ingredients is established by first calculating the predicted activity, p, of
the mixture based on
activities of the two components applied alone. If p is lower than the
experimentally established
effect, synergism has occurred. In the equation above, A is the fungicidal
activity in percentage
control of one component applied alone at rate x. The B term is the fungicidal
activity in
percentage control of the second component applied at rate y. The equation
estimates p, the
expected fungicidal activity of the mixture of A at rate x with B at rate y if
their effects are strictly
additive and no interaction has occurred.
TEST F
The test mixture was sprayed to the point of run-off on soybean seedlings. The
following
day the seedlings were inoculated with a spore suspension of Phakopsora
pachyrhizi (the causal
agent of Asian soybean rust) and incubated in a saturated atmosphere at 22 C
for 24 h and then
moved to a growth chamber at 22 C for 8 days, after which time visual disease
ratings were made.
Results for Test F are given in Tables B-1 through I-1 for Compound 32 and
Tables B-2
through 1-2 for Compound 64. Each table corresponds to a set of evaluations
performed together
at the same time. In each table, a rating of 100 indicates 100 % disease
control and a rating of 0
indicates no disease control (relative to the controls). Columns labeled
"Obsd" indicate the
average of results observed from test run on four individual plants. Columns
labeled "Exp"
indicate the expected value for each treatment mixture using the Colby
equation.
Table B-1
Observed and Expected Effects of Compound 32 Alone and Mixtures with
Picoxystrobin
in Controlling Asian Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
1.422 None 0 55
2.276 None 0 64
0 picoxystrobin 20.596 73
0 picoxystrobin 33.865 75
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
237
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd
Exp
Component (a))
1.422 picoxystrobin 20.596 75 88
1.422 picoxystrobin 33.865 66 89
2.276 picoxystrobin 20.596 66 90
2.276 picoxystrobin 33.865 72 91
Table B-2
Observed and Expected Effects of Compound 64 Alone and Mixtures with
Picoxystrobin
in Controlling Asian Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd
Exp
Component (a))
0 None 0 0
0.303 None 0 53
0.489 None 0 68
0 picoxystrobin 20.596 73
0 picoxystrobin 33.865 75
0.303 picoxystrobin 20.596 59 87
0.303 picoxystrobin 33.865 67 88
0.489 picoxystrobin 20.596 65 91
0.489 picoxystrobin 33.865 72 92
Table C-1
Observed and Expected Effects of Compound 32 Alone and Mixtures with Bixafen,
Fluxapyroxad and Fluindapyr in Controlling Asian Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd
Exp
Component (a))
0 None 0 0
1.422 None 0 39
2.276 None 0 44
0 bixafen 11.327 54
0 bixafen 19.525 55
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
238
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
1.422 bixafen 11.327 64 72
1.422 bixafen 19.525 59 72
2.276 bixafen 11.327 56 75
2.276 bixafen 19.525 59 74
0 fluxapyroxad 2.757 19
0 fluxapyroxad 4.748 52
1.422 fluxapyroxad 2.757 68 50
1.422 fluxapyroxad 4.748 74 70
2.276 fluxapyroxad 2.757 72 54
2.276 fluxapyroxad 4.748 82 73
0 fluindapyr 8.820 61
0 fluindapyr 15.230 79
1.422 fluindapyr 8.820 50 76
1.422 fluindapyr 15.230 51 87
2.276 fluindapyr 8.820 64 78
2.276 fluindapyr 15.230 71 88
Table C-2
Observed and Expected Effects of Compound 64 Alone and Mixtures with Bixafen,
Fluxapyroxad and Fluindapyr in Controlling Asian Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
0.303 None 0 34
0.489 None 0 63
0 bixafen 11.327 54
0 bixafen 19.525 55
0.303 bixafen 11.327 35 70
0.303 bixafen 19.525 66 69
0.489 bixafen 11.327 13 83
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
239
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0.489 bixafen 19.525 53 83
0 fluxapyroxad 2.757 19
0 fluxapyroxad 4.748 52
0.303 fluxapyroxad 2.757 27 46
0.303 fluxapyroxad 4.748 54 68
0.489 fluxapyroxad 2.757 53 70
0.489 fluxapyroxad 4.748 48 82
0 fluindapyr 8.820 61
0 fluindapyr 15.230 79
0.303 fluindapyr 8.820 64 74
0.303 fluindapyr 15.230 72 86
0.489 fluindapyr 8.820 61 86
0.489 fluindapyr 15.230 65 92
Table D-1
Observed and Expected Effects of Compound 32 Alone and Mixtures with Mancozeb,
Fenpropimorph and Tebuconazole in Controlling Asian Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
1.422 None 0 52
2.276 None 0 60
0 mancozeb 42.532 70
0 mancozeb 74.012 71
1.422 mancozeb 42.532 94 86
1.422 mancozeb 74.012 91 86
2.276 mancozeb 42.532 94 88
2.276 mancozeb 74.012 73 88
0 fenpropimorph 242.823 33
0 fenpropimorph 458.587 44
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
240
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
1.422 fenpropimorph 242.823 73 68
1.422 fenpropimorph 458.587 67 73
2.276 fenpropimorph 242.823 79 73
2.276 fenpropimorph 458.587 91 78
0 tebuconazole 486.921 30
0 tebuconazole 841.166 55
1.422 tebuconazole 486.921 52 66
1.422 tebuconazole 841.166 76 78
2.276 tebuconazole 486.921 64 72
2.276 tebuconazole 841.166 72 82
Table D-2
Observed and Expected Effects of Compound 64 Alone and Mixtures with Mancozeb,
Fenpropimorph and Tebuconazole in Controlling Asian Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
0.303 None 0 49
0.489 None 0 63
0 mancozeb 42.532 70
0 mancozeb 74.012 71
0.303 mancozeb 42.532 83 85
0.303 mancozeb 74.012 82 85
0.489 mancozeb 42.532 92 89
0.489 mancozeb 74.012 92 89
0 fenpropimorph 242.823 33
0 fenpropimorph 458.587 44
0.303 fenpropimorph 242.823 64 66
0.303 fenpropimorph 458.587 94 72
0.489 fenpropimorph 242.823 88 75
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
241
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0.489 fenpropimorph 458.587 92 79
0 tebuconazole 486.921 30
0 tebuconazole 841.166 55
0.303 tebuconazole 486.921 48 65
0.303 tebuconazole 841.166 54 77
0.489 tebuconazole 486.921 50 74
0.489 tebuconazole 841.166 66 83
Table E-1
Observed and Expected Effects of Compound 32 Alone and Mixtures with
Cyproconazole, Azoxystrobin and Trifloxystrobin in Controlling Asian Soybean
Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
1.422 None 0 78
2.276 None 0 80
0 cyproconazole 37.333 44
0 cyproconazole 64.883 68
1.422 cyproconazole 37.333 80 87
1.422 cyproconazole 64.883 82 93
2.276 cyproconazole 37.333 87 88
2.276 cyproconazole 64.883 87 93
0 azoxystrobin 95.873 70
0 azoxystrobin 169.226 88
1.422 azoxystrobin 95.873 85 93
1.422 azoxystrobin 169.226 90 97
2.276 azoxystrobin 95.873 87 94
2.276 azoxystrobin 169.226 86 98
0 trifloxystrobin 20.511 69
0 trifloxystrobin 35.310 86
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
242
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
1.422 trifloxystrobin 20.511 79 93
1.422 trifloxystrobin 35.310 94 97
2.276 trifloxystrobin 20.511 92 94
2.276 trifloxystrobin 35.310 94 97
Table E-2
Observed and Expected Effects of Compound 64 Alone and Mixtures with
Cyproconazole, Azoxystrobin and Trifloxystrobin in Controlling Asian Soybean
Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
0.303 None 0 78
0.489 None 0 77
0 cyproconazole 37.333 44
0 cyproconazole 64.883 68
0.303 cyproconazole 37.333 82 88
0.303 cyproconazole 64.883 80 93
0.489 cyproconazole 37.333 86 87
0.489 cyproconazole 64.883 90 93
0 azoxystrobin 95.873 70
0 azoxystrobin 169.226 88
0.303 azoxystrobin 95.873 84 93
0.303 azoxystrobin 169.226 85 97
0.489 azoxystrobin 95.873 91 93
0.489 azoxystrobin 169.226 87 97
0 trifloxystrobin 20.511 69
0 trifloxystrobin 35.310 86
0.303 trifloxystrobin 20.511 90 93
0.303 trifloxystrobin 35.310 87 97
0.489 trifloxystrobin 20.511 86 93
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
243
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd
Exp
Component (a))
0.489 trifloxystrobin 35.310 82 97
Table F-1
Observed and Expected Effects of Compound 32 Alone and Mixtures with
Epoxiconazole and Pydiflumetofen in Controlling Asian Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd
Exp
Component (a))
0 None 0 0
1.422 None 0 75
2.276 None 0 77
0 epoxiconazole 46.795 23
0 epoxiconazole 89.631 70
1.422 epoxiconazole 46.795 76 81
1.422 epoxiconazole 89.631 79 92
2.276 epoxiconazole 46.795 81 82
2.276 epoxiconazole 89.631 88 93
0 pydiflumetofen 70.950 0
0 pydiflumetofen 135.850 73
1.422 pydiflumetofen 70.950 61 75
1.422 pydiflumetofen 135.850 81 93
2.276 pydiflumetofen 70.950 84 77
2.276 pydiflumetofen 135.850 76 94
Table F-2
Observed and Expected Effects of Compound 64 Alone and Mixtures with
Epoxiconazole and Pydiflumetofen in Controlling Asian Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd
Exp
Component (a))
0 None 0 0
0.303 None 0 37
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
244
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0.489 None 0 68
0 epoxiconazole 46.795 23
0 epoxiconazole 89.631 70
0.303 epoxiconazole 46.795 58 52
0.303 epoxiconazole 89.631 68 81
0.489 epoxiconazole 46.795 69 76
0.489 epoxiconazole 89.631 73 90
0 pydiflumetofen 70.950 0
0 pydiflumetofen 135.850 73
0.303 pydiflumetofen 70.950 47 37
0.303 pydiflumetofen 135.850 66 83
0.489 pydiflumetofen 70.950 63 68
0.489 pydiflumetofen 135.850 63 92
Table G-1
Observed and Expected Effects of Compound 32 Alone and Mixtures with
Benzovindiflupyr, Prothioconazole and Chlorothalonil in Controlling Asian
Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
1.422 None 0 39
2.276 None 0 61
0 benzovindiflupyr 0.606 67
0 benzovindiflupyr 0.980 67
1.422 benzovindiflupyr 0.606 70 80
1.422 benzovindiflupyr 0.980 80 80
2.276 benzovindiflupyr 0.606 76 87
2.276 benzovindiflupyr 0.980 80 87
0 prothioconazole 10.165 7
0 prothioconazole 16.339 65
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
245
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
1.422 prothioconazole 10.165 72 43
1.422 prothioconazole 16.339 47 79
2.276 prothioconazole 10.165 71 64
2.276 prothioconazole 16.339 87 86
0 chlorothalonil 138.129 59
0 chlorothalonil 222.081 85
1.422 chlorothalonil 138.129 50 75
1.422 chlorothalonil 222.081 88 91
2.276 chlorothalonil 138.129 57 84
2.276 chlorothalonil 222.081 88 94
Table G-2
Observed and Expected Effects of Compound 64 Alone and Mixtures with
Benzovindiflupyr, Prothioconazole and Chlorothalonil in Controlling Asian
Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
0.303 None 0 52
0.489 None 0 50
0 benzovindiflupyr 0.606 67
0 benzovindiflupyr 0.980 67
0.303 benzovindiflupyr 0.606 83 84
0.303 benzovindiflupyr 0.980 79 84
0.489 benzovindiflupyr 0.606 73 83
0.489 benzovindiflupyr 0.980 86 84
0 prothioconazole 10.165 7
0 prothioconazole 16.339 65
0.303 prothioconazole 10.165 61 55
0.303 prothioconazole 16.339 69 83
0.489 prothioconazole 10.165 60 53
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
246
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0.489 prothioconazole 16.339 73 82
0 chlorothalonil 138.129 59
0 chlorothalonil 222.081 85
0.303 chlorothalonil 138.129 34 81
0.303 chlorothalonil 222.081 89 93
0.489 chlorothalonil 138.129 65 79
0.489 chlorothalonil 222.081 91 92
Table H-1
Observed and Expected Effects of Compound 32 Alone and Mixtures with
Pydiflumetofen, Pyraclostrobin and Metominostrobin in Controlling Asian
Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
1.422 None 0 69
2.276 None 0 63
0 pydiflumetofen 41.364 49
0 pydiflumetofen 128.793 36
1.422 pydiflumetofen 41.364 67 84
1.422 pydiflumetofen 128.793 72 80
2.276 pydiflumetofen 41.364 76 81
2.276 pydiflumetofen 128.793 83 76
0 pyraclostrobin 45.860 35
0 pyraclostrobin 137.503 45
1.422 pyraclostrobin 45.860 43 80
1.422 pyraclostrobin 137.503 65 83
2.276 pyraclostrobin 45.860 55 76
2.276 pyraclostrobin 137.503 78 79
0 metominostrobin 29.673 13
0 metominostrobin 86.003 37
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
247
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
1.422 metominostrobin 29.673 65 73
1.422 metominostrobin 86.003 52 80
2.276 metominostrobin 29.673 63 67
2.276 metominostrobin 86.003 82 76
Table H-2
Observed and Expected Effects of Compound 64 Alone and Mixtures with
Pydiflumetofen, Pyraclostrobin and Metominostrobin in Controlling Asian
Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
0.303 None 0 50
0.489 None 0 70
0 pydiflumetofen 41.364 49
0 pydiflumetofen 128.793 36
0.303 pydiflumetofen 41.364 64 75
0.303 pydiflumetofen 128.793 78 68
0.489 pydiflumetofen 41.364 71 84
0.489 pydiflumetofen 128.793 67 81
0 pyraclostrobin 45.860 35
0 pyraclostrobin 137.503 45
0.303 pyraclostrobin 45.860 70 68
0.303 pyraclostrobin 137.503 80 73
0.489 pyraclostrobin 45.860 68 80
0.489 pyraclostrobin 137.503 59 83
0 metominostrobin 29.673 13
0 metominostrobin 86.003 37
0.303 metominostrobin 29.673 52 57
0.303 metominostrobin 86.003 69 69
0.489 metominostrobin 29.673 46 74
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
248
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0.489 metominostrobin 86.003 66 81
Table I-1
Observed and Expected Effects of Compound 32 Alone and Mixtures with Copper
hydroxide, Flutriafol and Fenpropidin in Controlling Asian Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 32 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
1.422 None 0 63
2.276 None 0 71
0 copper hydroxide 3610.778 87
0 copper hydroxide 7371.507 65
1.422 copper hydroxide 3610.778 84 95
1.422 copper hydroxide 7371.507 81 87
2.276 copper hydroxide 3610.778 93 96
2.276 copper hydroxide 7371.507 87 90
0 flutriafol 544.265 13
0 flutriafol 1124.021 52
1.422 flutriafol 544.265 82 68
1.422 flutriafol 1124.021 87 82
2.276 flutriafol 544.265 75 75
2.276 flutriafol 1124.021 88 86
0 fenpropidin 78.393 45
0 fenpropidin 161.740 68
1.422 fenpropidin 78.393 48 80
1.422 fenpropidin 161.740 80 88
2.276 fenpropidin 78.393 83 84
2.276 fenpropidin 161.740 87 91
CA 03174932 2022-09-08
WO 2021/183707 PCT/US2021/021806
249
Table 1-2
Observed and Expected Effects of Compound 64 Alone and Mixtures with Copper
Hydroxide, Flutriafol and Fenpropidin in Controlling Asian Soybean Rust
Application Rate (ppm) Test F
Application Rate (ppm)
of Compound 64 (i.e. Component (b)
of Component (b) Obsd Exp
Component (a))
0 None 0 0
0.303 None 0 50
0.489 None 0 81
0 Copper Hydroxide 3610.778 87
0 Copper Hydroxide 7371.507 65
0.303 Copper Hydroxide 3610.778 79 93
0.303 Copper Hydroxide 7371.507 82 83
0.489 Copper Hydroxide 3610.778 86 97
0.489 Copper Hydroxide 7371.507 84 93
0 flutriafol 544.265 13
0 flutriafol 1124.021 52
0.303 flutriafol 544.265 65 56
0.303 flutriafol 1124.021 74 76
0.489 flutriafol 544.265 75 83
0.489 flutriafol 1124.021 75 91
0 fenpropidin 78.393 45
0 fenpropidin 161.740 68
0.303 fenpropidin 78.393 37 72
0.303 fenpropidin 161.740 77 84
0.489 fenpropidin 78.393 75 90
0.489 fenpropidin 161.740 82 94
