Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
CA 02386800 2002-04-05
WO 01/27093 PCT/EP00/09419
Alkylamino-1,3,5-triazines, process for their preparation and their use as
herbicides
and plant growth regulators
The invention relates to the technical field of crop protection agents, such
as
herbicides and plant growth regulators, in particular herbicides for the
selective control
of harmful plants in crops of useful plants.
It is known that 4-amino-2-[N-(1-arylalkyl)amino]-1,3,5-triazines which are
optionally
substituted in the 6 position on the triazine ring by optionally halogenated
hydrocarbon
"" groups or other groups, and their derivatives, have herbicidal and plant-
growth-
regulating properties; cf., for example, US-A-3816419, US-A-5290754 (WO-A-
90/9378,
EP-A-0411153), W095/06642, WO-A-97/31904, W098/15536, W098I42684,
WO-A-99/18100, WO-A-99/19309, WO-A-99/37627, W099/46249, JP-A-62,298,577,
JP-A-62,294,669, EP-A-0191496 and literature cited therein.
Some of the known active compounds have, when used, disadvantages, such as
insufficient herbicidal activity against harmful plants, too limited a
spectrum of harmful
plants which can be controlled with an active compound, or insufficient
selectivity in
crops of useful plants. Other active compounds cannot be prepared economically
on
an industrial scale, owing to reagents or precursors which are difficult to
obtain, or they
have insufficient chemical stability.
It is therefore desirable to provide alternative active compounds which can,
if
appropriate, advantageously, be employed as herbicides or plant-growth
regulators.
The present invention provides compounds of the formula (I) and salts thereof
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2
R~
R4 R5
N ~ N R3
R6 (I)
A N N
R2 R8 R~
in which
A a group of the formula NRaRb, in which
Ra and Rb, independently of one another, are hydrogen, formyl or else
aminocarbonyl or else amino(thiocarbonyl) or (C~-C~p)alkyl,
(C2-C~Q)alkenyl, (C2-C~p)alkynyl, (C~-C~p)alkylsulfinyl, (C~-C~p)alkyl-
sulfonyl, (C~-C~p)alkoxy, [(C~-C~p)alkyl]carbonyl, [(C~-C~p)alkoxy]-
carbonyl or else N-mono[(C~-C~p)alkyl]aminocarbonyl or else N,N-
di[(C~-C~p)alkyl]aminocarbonyl or else [(C~-C~p)alkylthio]carbonyl or else
[(C~-C~p)alkyl](thiocarbonyl) or else [(C~-C~p)alkoxy] (thiocarbonyl) or
else N-mono[(C~-C~p)alkyl]amino(thiocarbonyl) or else N,N-di[(C~-C~0)-
alkyl]amino(thiocarbonyl) or else [(C~-C~p)alkylthio](thiocarbonyl), where
,,., each of the 16 last-mentioned radicals is unsubstituted or substituted,
preferably unsubstituted or substituted by one or more radicals selected
from the group consisting of halogen, (C~-C4)alkoxy, (C~-Cq.)haloalkoxy,
(C~-C4)hydroxyalkoxy and (C~-Cq,)alkoxy-(C~-Cq.)alkoxy, or are
(C3-Cg)cycloalkyl, (C5-Cg)cycloalkenyl, (C3-Cg)cycloalkoxy,
(C5-Cg)cycloalkenyloxy, phenyl, phenoxy, phenylamino, phenylcarbonyl
or else naphthylcarbonyl or phenylsulfonyl, heterocyclyl, heterocyclyloxy,
heterocyclylamino, heterocyclylcarbonyl or heterocyclylsulfonyl, where
each of the 15 last-mentioned radicals is unsubstituted or substituted,
preferably unsubstituted or substituted by one or more radicals selected
from the group consisting of halogen, cyano, hydroxyl, (C~-C4)alkyl,
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(C~-C4)haloalkyl, (C~-C4)hydroxyalkyl, (C~-C4)alkoxy-(C~-C4)alkyl,
(C~-C4)alkoxy, (C~-C4)haloalkoxy, (C~-C4)hydroxyalkoxy and
(C1-C4)alkoxy-(C1-C4)alkoxy and heterocyclyl in the radicals mentioned
is in each case heterocyclyl having 3 to 9 ring atoms, 1 to 4 of which are
hetero ring atoms selected from the group consisting of N, O and S, or
one of the radicals Ra and Rb is as defined above and the other of the
radicals
Ra and Rb is a group of the formula NR'R", where R' and R",
independently of one another, are H or (C~-C6)alkyl which is
.~ unsubstituted or substituted, preferably unsubstituted or substituted by
one or more radicals selected from the group consisting of halogen,
hydroxyl, (C~-C4)alkoxy, (C1-C4)haloalkoxy, (C1-C4)hydroxyalkoxy and
(C1-C4)alkoxy-(C1-C4)alkoxy, or R' and R" together are straight-chain
(C2-C5)alkylene which is unsubstituted or substituted by one or more
radicals selected from the group consisting of (C~-C4)alkyl,
(C~-C4)alkoxy and (C1-C4)alkoxy-(C~-C4)alkyl, or
Ra and Rb together are (C~-C~p)alkylidene which is unsubstituted or
substituted
by one or more radicals selected from the group consisting of halogen,
,,.~, cyano, (Ct-C4)alkoxy, (C~-C4)haloalkoxy and (Ct-C4)alkylthio, or
NRaRb together are a heterocyclyl radical which is attached to the nitrogen
atom and has 3 to 6 ring atoms and, in addition to the nitrogen atom as
hetero ring atom, optionally contains 1 to 3 further hetero ring atoms
selected from the group consisting of N, O and S, where the heterocycle
is unsubstituted or substituted, preferably unsubstituted or substituted by
one or more radicals selected from the group consisting of halogen,
cyano, hydroxyl, (C~-C4)alkyl, (C~-C4)haloalkyl, (C1-C4)hydroxyalkyl,
(C~-C4)alkoxy, (C~-C4)haloalkoxy, (C~-C4)hydroxyalkoxy, (C~-C4)alkoxy-
(C~-C4)alkoxy, (C~-C4)alkoxy-(C~-C4)alkyl and oxo,
or
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A is (C1-Cg)alkyl, (C2-Cg)alkenyl, (C2-Cg)alkynyl, (Cg-Cs)cycloalkyl or
(C5-Cg)cycloalkenyl, where each of the 5 last-mentioned radicals is
unsubstituted or substituted, preferably unsubstituted or substituted by one
or
more radicals selected from the group consisting of halogen, (C~-C4)alkoxy,
(Ct-C4)haloalkoxy, (C~-C4)alkylthio, (C1-C4)alkoxy-(C~-C4)alkoxy and, in the
case of cyclic radicals, also (C~-C4)alkyl, (C1-C4)haloalkyl and (C~-C4)alkoxy-
(C~-C4)alkyl, and
R~ is hydroxyl, or
(C~-C~p)alkyl, which is unsubstituted or substituted by one or more radicals
selected from the group consisting of halogen, hydroxyl, cyano, nitro,
thiocyanato, formyl, amino, (C1-C4)alkoxy, (C~-C4)haloalkoxy, (C2-
C4)alkenyloxy, (C2-C4)haloalkenyloxy, (C2-C4)alkynyloxy, (C2-
C4)haloalkynyloxy, N-mono(C~-C4)alkylamino, N,N-di(C1-C4)alkylamino, (C~-
C4)alkylthio, (C1-C4)alkylsulfinyl, (C~-C4)haloalkylsulfinyl, (C~-
C4)alkylsulfonyl,
(C~-C4)haloalkylsulfonyl, [(C~-C4)alkyl]carbonyl, [(C~-C4)haloalkyl]carbonyl,
[(C~-C4)alkoxy]carbonyl, (C3-C9)cycloalkyl, (C5-Cg)cycloalkenyl, phenyl and
heterocyclyl, where each of the 4 last-mentioned radicals is unsubstituted or
'"'~ substituted, preferably unsubstituted or substituted by one or more
radicals
selected from the group consisting of halogen, cyano, hydroxyl, (C~-C4)alkyl,
(C~-C4)haloalkyl, (C2-C4)alkenyl, (C2-C4)haloalkenyl, (C2-C4)alkynyl,
(C2-C4)haloalkynyl, (Ct-C4)alkoxy, (C~-C4)haloalkoxy and (Ct-C4)alkylthio, and
heterocyclyl in the 5 last-mentioned radicals contains in each case 3 to 9
ring
atoms, 1 to 4 of which are hetero ring atoms selected from the group
consisting
of N, O and S, or
is [(C~-Cg)alkyl]carbonyl, [(C~-Cg)alkoxy]carbonyl, (C~-Cg)alkylsulfinyl or
(C1-
C4)alkylsulfonyl, where each of the 4 last-mentioned radicals is unsubstituted
or
substituted, preferably unsubstituted or substituted by one or more radicals
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selected from the group consisting of halogen, (C1-C4)alkoxy,
(C~-C4)haloalkoxy and (C1-C4)alkylthio, or
is (C3-Cg)cycloalkyl, which is unsubstituted or substituted, (Cs-
Cs)cycloalkenyl,
which is unsubstituted or substituted, where preferably each of the two last-
5 mentioned cyclic radicals is unsubstituted or substituted by one or more
radicals
selected from the group consisting of halogen, cyano, (C~-C4)alkyl,
(C1-C4)haloalkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (Ct-C4)alkoxy,
(C~-C4)haloalkoxy and (C1-C4)alkylthio,
~"" where the radical Rt , including substituents, preferably has 1 to 30
cartaon
atoms, in particular 1 to 20 carbon atoms,
R2 is H or formyl, (C1-C~p)alkyl, (C2-C~p)alkenyl, (C2-C~p)alkynyl,
(C1-C~p)alkylsulfinyl, (C~-C~p)alkylsulfonyl, (Ct-C~p)alkoxy,
[(C~-C~p)alkyl]carbonyl, [(C~-C~p)alkoxy]carbonyl, where each of the 8 last-
mentioned radicals is unsubstituted or substituted, preferably unsubstituted
or
substituted by one or more radicals selected from the group consisting of
halogen, (Ct-C4)alkoxy, (C~-C4)haloalkoxy and (Ct-C4)hydroxyalkoxy and also
(C~-C4)alkoxy-(C1-C4)alkoxy, or
,,~.. is (Cg-C6)cycloalkyl, (C5-Cs)cycloalkenyl, (C3-C6)cycloalkoxy, (C5-
Cg)cycloalkenyloxy, phenyl, phenoxy, phenylamino, phenylcarbonyl,
phenylsulfonyl, heterocyclyl, heterocyclyloxy, heterocyclylamino,
heterocyclylcarbonyl or heterocyclylsulfonyl, where each of the 14 last-
mentioned radicals is unsubstituted or substituted and heterocyclyl in the 5
last-
mentioned radicals preferably contains in each case 3 to 9 ring atoms, 1 to 4
of
which are hetero ring atoms selected from the group consisting of N, O and S,
where preferably each of the 14 radicals mentioned is unsubstituted or
substituted by one or more radicals selected from the group consisting of
halogen, cyano, hydroxyl, (C~-C4)alkyl, (C~-C4)haloalkyl, (C~-C4)hydroxyalkyl,
(C~-C4)alkoxy, (C~-C4)haloalkoxy and (C~-C4)hydroxyalkoxy and also
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(C~-C4)alkoxy-(C~-C4)alkoxy, or
is a group of the formula NR°Rd, where R° and Rd, independently
of one
another, are H, formyl, (C~-Cg)alkyl, (C2-C6)alkenyl, (C2-Cg)alkynyl,
(C~-Cg)alkylsulfinyl, (C~-Cg)alkylsulfonyl, (C~-Cg)alkoxy, [(C~-
Cg)alkyl]carbonyl
or [(C~-Cg)alkoxy]carbonyl, where each of the 8 last-mentioned groups is
unsubstituted or substituted, preferably unsubstituted or substituted by one
or
more radicals selected from the group consisting halogen, hydroxyl,
(C~-C4)alkoxy, (C~-C4)haloalkoxy, (C~-C4)hydroxyalkoxy and (C~-C4)alkoxy-
(C~-C4)alkoxy, or
R~ and Rd together are straight-chain (C2-C5)alkylene, which is unsubstituted
or
substituted by one or more radicals selected from the group consisting of
(C~-C4)alkyl, (C~-C4)alkoxy, (C~-C4)alkoxy-(C~-C4)alkyl and oxo,
R3 is halogen, CN, N02, SCN or a radical of the formula -X~-A~, where
X~ is a direct bond or a divalent group of the formula -O-, -S(O)p-, -S(O)p-O-
,
-O-S(O)p-, -CO-, -O-CO-, -CO-O-, -S-CO-, -CO-S-, -S-CS-, -CS-S-,
-O-CO-O-, -NR~ -, -O-NR~-, -NR~-O-, -NR~-CO-, -CO-NR~-,
-O-CO-NR~- or -NR~-CO-O-, in which in each case p is the integer 0, 1
'""~ or 2 and R~ is hydrogen, (C~-Cg)alkyl, (C2-Cg)alkenyl, (C2-Cg)alkynyl,
phenyl, phenyl-(C~-Cg)alkyl, (C3-Cg)cycloalkyl or [(C~-Cg)alkyl]carbonyl,
and
A~ is hydrogen, (C~-C~p)alkyl, (C2-C~p)alkenyl, (C2-C~p)alkynyl, (C3-
Cg)cycloalkyl, (C5-Cg)cycloalkenyl, phenyl or heterocyclyl having 3 to 9
ring atoms and 1 to 4 hetero ring atoms selected from the group
consisting of N, O and S, where each of the 7 last-mentioned radicals is
unsubstituted or substituted, preferably unsubstituted or substituted by
one or more radicals selected from the group consisting of halogen,
cyano, hydroxyl, (C~-C4)alkyl, (C3-Cg)cycloalkyl, (C~-C4)alkoxy,
(C~-C4)haloalkoxy and (C~-C4)hydroxyalkoxy and, in the case of cyclic
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radicals, also (C~-C4)haloalkyl, (C~-C4)alkoxy-(C~-C4)alkyl and
(C~-C4)hydroxyalkyl and, including substituents, has preferably up to 20
carbon atoms,
each of the radicals R4, R5, R6, R' and R8, independently of one another, is
halogen,
nitro, cyano, thiocyanato or a radical of the formula -X2-A2, where
X2 is a direct bond or a divalent group of the formula -O-, -S(O)q-,
-S(O)q-O-, -O -S(O)q-, -S(O)q-NR'-, -NR'-S(O)q-, -CO-, -O-CO-, -CO-O-,
-S-CO-, -CO-S-, -S-CS-, -CS-S-, -O-CO-O-, -NR' -, -O-NR'-, -NR'-O-,
-NR'-CO-, -CO-NR'-, -O-CO-NR'- or -NR'-CO-O-, in which in each case q
is the integer 0, 1 or 2 and R' is hydrogen, amino, substituted amino,
(C~-Cg)alkyl, (C2-Cg)alkenyl, (C2-Cg)alkynyl, phenyl, phenyl-(C~-
Cg)alkyl, phenylcarbonyl, (C3-Cg)cycloalkyl, (C5-Cg)cycloalkenyl,
[(C~-Cg)alkyl]carbonyl, (C~-Cg)alkylsulfonyl, (C~-Cg)alkylsulfinyl,
phenylsulfonyl or phenylsulfinyl, where each of the 13 last-mentioned
radicals is unsubstituted or substituted, preferably unsubstituted or
substituted by one or more radicals selected from the group consisting of
halogen, cyano, hydroxyl, (C~-C4)alkyl, (C~-C4)alkoxy,
(C~-C4)haloalkoxy and (C~-C4)hydroxyalkoxy and, in the case of cyclic
"~ radicals, also (C~-C4)haloalkyl, (C~-C4)alkoxy-(C~-C4)alkyl and
(C~-C4)hydroxyalkyl, and
A2 is hydrogen, (C~-C~p)alkyl, (C2-C~p)alkenyl, (C2-C~p)alkynyl,
(C3-Cg)cycloalkyl, (C~-Cg)cycloalkenyl, phenyl or heterocyclyl, where
each of the 7 last-mentioned radicals is unsubstituted or substituted,
preferably unsubstituted or substituted by one or more radicals selected
from the group consisting of halogen, cyano, hydroxyl, amino, mercapto,
aminocarbonyl, mono- and di(C~-Cg)alkylamino, mono- and diarylamino,
N-(C~-Cg)alkyl-N-arylamino, mono- and diacylamino, N-(C~-Cg)alkyl-N-
acylamino, N-aryl-N-acylamino, (C~-Cg)alkoxy, (C~-Cg)alkylthio,
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(C~-Cg)alkylsulfonyl, (C~-Cg)alkylsulfinyl, [(C~-C5)alkyl]carbonyl,
[(C~-C5)alkoxy]carbonyl, [(C~-Cg)alkyl]carbonyloxy, (Cg-Cg)cycloalkyl,
(Cg-Cg)cycloalkoxy, (C3-Cg)cycloalkylcarbonyl,
(C3-Cg)cycloalkylcarbonyloxy, phenyl, phenoxy, phenylthio,
phenylcarbonyl, phenylcarbonyloxy, heterocyclyl, heterocyclyloxy,
heterocyclylthio, heterocyclylcarbonyl, heterocycly~arbonyloxy and, in
the case of cyclic radicals, also (C~-Cg)alkyl,
where each of the 31 last-mentioned radicals is unsubstituted or
substituted, preferably unsubstituted or substituted by one or more
radicals selected from the group consisting of halogen, cyano,
hydroxyl, amino, mono- and di(C~-Cg)alkylamino, mono- and di-
arylamino, N-(C~-Cg)alkyl-N-arylamino, mono- and di-
(C~-Cg)acylamino, N-(Ct-Cg)alkyl-N-acylamino, (C~-Cg)alkoxy,
(C~-Cg)alkylthio, (Cg-Cg)cycloalkyl, (Cg-Cg)cycloalkoxy, phenyl,
phenoxy and phenylthio and, in the case of cyclic radicals, also
(C1-Cg)alkyl, (C1-C6)haloalkyl and (C~-C4)alkoxy-(C1-Cs)alkyl and
where heterocyclyl in A2 in each case contains 3 to 9 ring atoms
and 1 to 4 hetero ring atoms selected from the group consisting of
'"~"' N, O and S,
and where A2, including substituents, has preferably up to 20 carbon
atoms,
or
two adjacent radicals from the group consisting of R4, R5, R6, R' and Rg
together with the carbon atoms of the phenyl ring to which they are attached
form a fused ring having 4 to 6 ring atoms which is carbocyclic or contains 1
to
3 hetero ring atoms from the group consisting of N, O and S and which is
unsubstituted or substituted by one or more radicals selected from the group
consisting of halogen, (C1-C6)alkyl, iC~-Cg)haloalkyl, (C2-Cg)alkenyl, (C2-
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Cg)alkynyl, (C~-Cg)alkoxy, [(C~-Cg)haloalkoxy, (C1-Cg)alkyl]carbonyl,
[(C1-Cg)alkoxyJcarbonyl, (C~-Cg)alkylsulfonyl and (C1-Cg)alkylsulfinyl,
where at least two radicals, preferably 2 or 3 radicals, in particular 2
radicals,
selected from the group consisting of R4, R5, R6, R' and R$ are different from
hydrogen,
except for compounds of the formula (I) and salts thereof in which
A is NH2,
R1 is a radical of the formula -C(CH3)(X*)(R*), in which X* = halogen and R* =
H,
CHg or C2H5,
R2 is H,
R3 is CHg,
R5 is CH3 or OCH3,
R6 is CH3 or OCH3
and
R4, R' and Re are each H.
The last-mentioned compounds (I), which are excluded, are already known from
US-A-5290754 (VIIO-A-90/9378, EP-A-0411153).
Unless defined otherwise, divalent radicals, for example X~ - -CO-NR~-, are
defined
such that in the composed groups, for example -X1-A~, the bond of the divalent
radical
linked to the group A~ is the bond which is written on the right in the
formula for the
divalent radical, i.e. -X~-A1 is a group of the formula -CO-NR~-A1; this
applies
correspondingly to analogous divalent radicals.
The invention also provides all stereoisomers which are embraced by the
formula (I),
and mixtures thereof. Such compounds of the formula (I) contain one or more
asymmetrically substituted carbon atoms or else double bonds, which are not
specifically mentioned in the general formulae (I). The possible
stereoisomers, which
are defined by their specific steric form, such as enantiomers, diastereomers,
including
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Z and E isomers, are all embraced by the formula (I) and can be obtained by
customary methods from mixtures of the stereoisomers or else be prepared by
stereoselective reactions in combination with the use of stereochemically pure
or
enriched starting materials. Of particular interest are also the stereoisomers
which
5 result from the asymmetrically substituted carbon atom to which the group R3
is
attached, if R3 is not hydrogen. The isomers which are R- and S-configured at
this
center, which represent enantiomers, if no further asymmetrically substituted
carbon
atom is present in the molecule of the formula (I), therefore also form part
of the
subject matter of the invention. In general, the biological activities of
these R and S
10 isomers are not identical, but in the individual case, depending on the
species of
harmful plant and the crop, one of the isomers has a higher herbicidal action
or
selectivity.
If compounds of the formula (I) are also capable of forming tautomers whose
structure
is formally not represented or included in the formula (1), these tautomers
are
nevertheless embraced by the definition of the compounds of the formula (I)
according
to the invention.
The compounds of the formula (I) can form salts by addition of a suitable
inorganic or
organic acid, such as, for example, HCI, HBr, H2S04 or HN03, but also oxalic
acid or
sulfonic acids, to a basic group, such as, for example, amino or alkylamino.
Suitable
substituents which are present in deprotonated form, such as, for example,
sulfonic
acids or carboxylic acids, can form inner salts with groups which for their
part can be
protonated, such as amino groups. Salts can also be formed by replacing the
hydrogen of suitable substituents, such as, for example, sulfonic acids or
carboxylic
acids, by an agriculturally suitable cation. These salts are, for example,
metal salts, in
particular alkali metal salts or alkaline earth metal salts, in particular
sodium salts and
potassium salts, or else ammonium salts or salts with organic amines.
In the formula (I) and all the formulae hereinbelow, the radicals alkyl,
alkoxy, haloalkyl,
haloalkoxy, alkylamino and alkylthio and the corresponding unsaturated and/or
substituted radicals can in each case be straight-chain or branched in the
carbon
skeleton. Unless specifically mentioned otherwise, the lower carbon skeletons,
for
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example with 1 to 6 carbon atoms or in the case of unsaturated groups with 2
to 6
carbon atoms are preferred for these radicals. Alkyl radicals, also in the
composed
meanings, such as alkoxy, haloalkyl, and the like, are, for example, methyl,
ethyl, n- or
isopropyl, n-, i-, t- or 2-butyl, pentyls, hexyls, such as n-hexyl, isohexyl
and
1,3-dimethylbutyl, heptyls, such as n-heptyl, 1-methylhexyl and 1,4-
dimethylpentyl;
alkenyl and alkynyl radicals have the meaning of the possible unsaturated
radicals
which correspond to the alkyl radicals; alkenyl is, for example, allyl,
1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1-yl,
1-methyl-
but-3-en-1-yl and 1-methyl-but-2-en-1-yl; alkynyl is, for example, propargyl,
but-2-yn-
1-yl, but-3-yn-1-yl, 1-methylbut-3-yn-1-yl.
Alkylidene, for example in the form (C~-C~p)alkylidene, is the radical of a
straight-chain
or branched alkane which is attached via a double bond, the position of the
binding
site not yet being fixed. In the case of a branched alkane, the only possible
positions
are, of course, those where two hydrogen atoms can be replaced by the double
bond;
examples of radicals are =CH2, =CH-CH3, =C(CH3)-CHg, =C(CH3)-C2H5 or
=C(C2H5)-C2H5.
Cycloalkyl is a carbocyclic saturated ring system having preferably 3-8 carbon
atoms,
for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. In the case of
substituted cycloalkyl, this includes cyclic systems with substituents, where
the
A..,
substitutents are attached to the cycloalkyl radical via a double bond, for
example an
alkylidene group such as methylidene. Substituted cycloalkyl also includes
polycyclic
aliphatic systems, such as, for example, bicyclo[1.1.0]butan-1-yl,
bicyclo[1.1.0]butan-2-
y1, bicyclo[2.1.0]pentan-1-yl, bicyclo[2.1.0]pentan-2-yl, bicyclo[2.1.0]pentan-
5-yl,
adamantan-1-yl and adamantan-2-yl.
Cycloalkenyl is a carbocyclic non-aromatic, partially unsaturated ring system
having
preferably 4-8 carbon atoms, for example 1-cyclobutenyl, 2-cyclobutenyl,
1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, or 1-cyclohexenyl, 2-
cyclohexenyl,
3-cyclohexenyl, 1,3-cyclohexadienyl or 1,4-cyclohexadienyl. For substituted
cycloalkenyl, the illustrations for substituted cycloalkyl apply
correspondingly.
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Halogen is, for example, fluorine, chlorine, bromine or iodine. Haloalkyl, -
alkenyl and
-alkynyl are alkyl, alkenyl and alkynyl, respectively, which are partially or
fully
substituted by halogen, preferably by fluorine, chlorine and/or bromine, in
particular by
fluorine or chlorine, for example, monohaloalkyl, perhaloalkyl, CFg, CHF2,
CH2F,
CF3CF2, CH2FCHC1, CCIg, CHCI2, CH2CH2C1; haloalkoxy is, for example, OCFg,
OCHF2, OCH2F, CF3CF20, OCH2CF3 and OCH2CH2CI; this applies correspondingly
to haloalkenyl and other halogen-substituted radicals.
Aryl is a mono-, bi- or polycyclic aromatic system, for example phenyl,
naphthyl,
",~"10 tetrahydronaphthyl, indenyl, indanyl, pentalenyl, fluorenyl and the
like, preferably
phenyl.
A heterocyclic radical or ring (heterocyclyi) can be saturated, unsaturated or
heteroaromatic; unless defined otherwise, it preferably contains one or more,
in
particular 1, 2 or 3, heteroatoms in the heterocyclic ring, preferably
selected from the
group consisting of N, O and S; it is preferably an aliphatic heterocyclyl
radical having
3 to 7 ring atoms or a heteroaromatic radical having 5 or 6 ring atoms. The
heterocyclic radical can, for example, be a heteroaromatic radical or ring
(heteroaryl),
such as, for example, a mono-, bi- or polycyclic aromatic system, in which at
least 1
ring contains one or more heteroatoms. It is preferably a heteroaromatic ring
having
one heteroatom selected from the group consisting of N, O and S, for example
pyridyl,
pyrrolyl, thienyl or furyl; furthermore, preferably, it is a corresponding
heteroaromatic
ring having 2 or 3 heteroatoms, for example pyrimidinyl, pyridazinyl,
pyrazinyl, triazinyl,
thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl and
triazolyl.
Furthermore preferably, it is a partially or fully hydrogenated heterocyclic
radical
having one heteroatom selected from the group consisting of N, O and S, for
example
oxiranyl, oxetanyl, oxolanyl (= tetrahydrofuryl), oxanyl, pyrrolidyl or
piperidyl.
Furthermore preferably, it is a partially or fully hydrogenated heterocyclic
radical
having 2 heteroatoms selected from the group consisting of N, O and S, for
example
piperazinyl, dioxolanyl, oxazolinyl, isoxazolinyl, oxazolidinyl,
isoxazolidinyl and
morpholinyl.
Possible substituents for a substituted heterocyclic radical are the
substituents
mentioned further below, and addit'ronally also oxo. The oxo group can also be
present
CA 02386800 2002-04-05
13
at the hetero ring atoms which can exist in different oxidation states, for
example at N
and S.
Substituted radicals, such as a substituted alkyl, alkenyl, alkynyl, aryl,
phenyl, benryl,
heterocyclyl and heteroaryl radical, are, for example, a substituted radical
derived from
the unsubstituted skeleton, where the substituents are, for example, one or
more,
preferably 1, 2 or 3, radicals selected from the group consisting of halogen,
alkoxy,
haloalkoxy, alkylthio, hydroxyl, amino, nitro, carboxyl, cyano, azido,
alkoxycarbonyl,
alkylcarbonyl, formyl, carbamoyl, mono- and dialkylaminocarbonyl, substituted
amino,
such as acylamino, mono- and dialkylamino, and alkylsulfinyl,
haloalkylsulfinyl,
,,,." alkylsulfonyl, haloalkylsulfonyl and, in the case of cyclic radicals,
also alkyl, haloalkyl
alkylthioalkyl, alkoxyalkyl, optionally substituted mono- and
dialkylaminoalkyl and
hydroxyalkyl; the term "substituted radicals", such as substituted alkyl and
the like,
includes as substituents, in addition to the saturated hydrocarbon-containing
radicals
mentioned, the corresponding unsaturated aliphatic and aromatic radicals, such
as
unsubstituted or substituted alkenyl, alkynyl, alkenyloxy, alkynyloxy, phenyl,
phenoxy
etc. Substituted cyclic radicals having aliphatic moieties in the ring include
cyclic
systems having substituents which are attached to the ring via a double bond,
for
example those substituted by an alkylidene group, such as methylidene or
ethylidene.
Among the radicals with carbon atoms, preference is given to those having 1 to
4
carbon atoms, in particular 1 or 2 carbon atoms. In general, preference is
given to
substituents selected from the group consisting of halogen, for example
fluorine and
chlorine, (C~-C4)alkyl, preferably methyl or ethyl, (C~-C4)haloalkyl,
preferably
trifluoromethyl, (C~-C4)alkoxy, preferably methoxy or ethoxy, (C~-
C4)haloalkoxy, nitro
and cyano. Particular preference is given here to the substituents methyl,
methoxy,
fluorine and chlorine.
Substituted amino, such as mono- or disubstituted amino, is a radical from the
group
of the substituted amino radicals which are N-substituted, for example, by one
or two
identical or different radicals selected from the group consisting of alkyl,
alkoxy, acyl
and aryl; preferably mono- and dialkylamino, mono- and diarylamino, acylamino,
N-alkyl-N-arylamino, N-alkyl-N-acylamino and N-heterocycles; preference is
given to
alkyl radicals having 1 to 4 carbon atoms; aryl is preferably phenyl or
substituted
CA 02386800 2002-04-05
14
phenyl; for acyl, the definition mentioned further below applies, preferably
(C1-C4)alkanoyl. This applies correspondingly to substituted hydroxylamino or
hydrazino.
Unsubstituted or substituted phenyl is preferably phenyl which is
unsubstituted or
mono- or polysubstituted, preferably up to trisubstituted, by identical or
different
radicals selected from the group consisting of halogen, (C1-C4)alkyl, (C~-
C4)alkoxy,
(C1-C4)haloalkyl, (C~-C4)haloalkoxy and nitro, for example o-, m- and p-tolyl,
dimethylphenyls, 2-, 3- and 4-chlorophenyl, 2-, 3- and 4-trifluoro- and -
trichlorophenyl,
X10 2,4-, 3,5-, 2,5- and 2,3-dichlorophenyl, o-, m- and p-methoxyphenyl.
Acyl is a radical of an organic acid which is formally formed by removing a
hydroxyl
group from the acid function, where the organic radical in the acid can also
be
attached to the acid function via a heteroatom. Examples of aryl are the
radical -CO-R
of a carboxylic acid HO-CO-R and radicals of acids derived therefrom, such as
thiocarbonic acid, unsubstituted or N-substituted iminocarboxylic acids or the
radical of
carbonic monoesters, N-substituted carbamic acid, sulfonic acids, sulfinic
acids,
N-substituted sulfonamide acids, phosphonic acids, phosphinic acids.
Acyl is, for example, formyl, alkylcarbonyl, such as [(C1-C4)alkyl]carbonyl,
phenylcarbonyl, alkyloxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl,
''' alkylsulfonyl, alkylsulfinyl, N-alkyl-1-iminoalkyl and other radicals of
organic acids. The
radicals can in each case be further substituted in the alkyl or phenyl
moiety, for
example in the alkyl moiety by one or more radicals selected from the group
consisting
of halogen, alkoxy, phenyl and phenoxy; examples of substituents in the phenyl
moiety
are the substituents which have already been mentioned further above generally
for
substituted phenyl.
Acyl is preferably an acyl radical in the more restricted sense, i.e. a
radical of an
organic acid where the acid group is directly attached to the carbon atom of
an organic
radical, for example formyl, alkylcarbonyl, such as acetyl or [(C1-
C4)alkyl]carbonyl,
phenylcarbonyl, alkylsulfonyl, alkylsulfinyl and other radicals of organic
acids.
In particular for reasons of better herbicidal activity, better selectivity
and/or easier
CA 02386800 2002-04-05
preparation, the novel compounds of the formula (I) mentioned or their salts
of
particular interest are those in which individual radicals have one of the
preferred
meanings already mentioned or mentioned hereinbelow, or, in particular, those,
in
which one or more of the preferred meanings already mentioned or mentioned
5 hereinbelow are combined.
Of interest are, for example, compounds of the formula (I) according to the
invention or
salts thereof in which
A is a group of the formula NRaRb, in which
~ 10 Ra and R~, independently of one another, are hydrogen, formyl or else
aminocarbonyl or else amino(thiocarbonyl) or (C1-Cg)alkyl,
(C2-Cg)alkenyl, (C2-Cs)alkynyl, (C~-Cs)alkylsulfinyl, (C~-C6)alkylsulfonyl,
(C~-Cg)alkoxy, [(C~-Cg)alkyl]carbonyl, [(C~-Cg)alkoxy]carbonyl or else
N-mono[ (C1-Cg)alkyl]aminocarbonyl or else N,N-
15 di[(C1-Cg)alkyl]aminocarbonyl or else [(C~-C6)alkylthio]carbonyl or else
[(C1-Cg)alkyl](thiocarbonyl) or else [(C1-Cg)alkoxy] (thiocarbonyl) or else
N-mono[(C~-Cg)alkyl]amino(thiocarbonyl) or else N,N-
di[(C~-C6)alkyl]amino(thiocarbonyl) or else
[(C~-Cg)alkylthio](thiocarbonyl), where each of the 16 last-mentioned
radicals is unsubstituted or substituted, preferably unsubstituted or
substituted by one or more radicals selected from the group consisting of
halogen, (C~-C4)alkoxy, (C~-C4)haloalkoxy, (C~-C4)hydroxyalkoxy and
(C~-C4)alkoxy-(C~-C4)alkoxy, or
are (C3-C6)cycloalkyl, (C3-Cg)cycloalkoxy, phenyl, phenoxy,
phenylamino, phenylcarbonyl or else naphthylcarbonyl or phenylsulfonyl,
heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclylcarbonyl,
heterocyclylsulfonyl, where each of the 13 last-mentioned radicals is
unsubstituted or substituted, preferably unsubstituted or substituted by
one or more radicals selected from the group consisting of halogen,
CA 02386800 2002-04-05
16
cyano, (C~-C4)alkyl, (C~-C4)haloalkyl, (C~-C4)alkoxy-(C~-C4)alkyl,
(C~-C4)alkoxy, (C~-C4)haloalkoxy and (C~-C4)alkoxy-(C~-C4)alkoxy, and
heterocyclyl in the radicals mentioned is in each case heterocyclyl having
3 to 9 ring atoms, 1 to 3 of which are hetero ring atoms selected from the
group consisting of N, O and S, or
one of the radicals Ra and Rb is as defined above and the other of the
radicals
Ra and Rb is a group of the formula NR'R", where R' and R",
independently of one another, are H or (C1-C4)alkyl, which is
unsubstituted or substituted, preferably unsubstituted or substituted by
one or more radicals selected from the group consisting of halogen,
(C~-C4)alkoxy, (C~-C4)haloalkoxy and (C~-C4)alkoxy-(C~-C4)alkoxy, or
R' and R" together are straight-chain (C2-C5)alkylene, which is
unsubstituted or substituted by one or more radicals selected from the
group consisting of (C~-C4)alkyl, (C1-C4)alkoxy and (C~-C4)alkoxy-
(C~-C4)alkyl, or
Ra and Rb together are (C~-Cg)alkylidene, which is unsubstituted or
substituted
by one or more radicals selected from the group consisting of halogen,
cyano, (C~-C4)alkoxy, (C~-C4)haloalkoxy and (C1-C4)alkylthio, or
NRaRb together are a heterocyclyl radical which is attached to the nitrogen
atom and has 3 to 6 ring atoms and, in addition to the nitrogen atom as
hetero ring atom, optionally contains 1 to 3 further hetero ring atoms
selected from the group consisting of N, O and S, where the heterocycle
is unsubstituted or substituted, preferably unsubstituted or substituted by
one or more radicals selected from the group consisting of halogen,
cyano, (C~-C4)alkyl, (C~-C4)haloalkyl, (C1-C4)alkoxy, (C~-C4)haloalkoxy,
(C~-C4)alkoxy-(C~-C4)alkoxy and (C~-C4)alkoxy-(C1-C4)alkyl,
or
A is (C~-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl or (C3-C4)cycloalkyl, where
each
of the 4 last-mentioned radicals is unsubstituted or substituted, preferably
CA 02386800 2002-04-05
17
unsubstituted or substituted by one or more radicals selected from the group
consisting of halogen, (C~-C4)alkoxy, (C~-C4)haloalkoxy, (C1-C4)alkylthio,
(C~-C4)alkoxy-(C1-C4)alkoxy and, in the case of cyclic radicals, also
(C~-C4)alkyl, (C1-C4)haloalkyl and (C~-C4)alkoxy-(C1-C4)alkyl,
preferably (C~-C3)alkyl, in particular methyl.
Preference is given to compounds of the formula (I) according to the invention
or salts
thereof in which
A is a group of the formula NRaRb, in which
Ra is hydrogen or (C~-C4)alkyl and
Rb is hydrogen or formyl, or else aminocarbonyl or else amino(thiocarbonyl) or
(C~-C4)alkyl, (C~-C4)alkylsulfonyl, [(C~-C4)alkyl]carbonyl or [(C~-
C4)alkoxy]carbonyl,
where each of the 4 last-mentioned radicals is unsubstituted or substituted by
one or
more radicals selected from the group consisting of halogen and (Ct-C4)alkoxy,
or
is (Cg-Cg)cycloalkyl, phenyl, phenoxy, phenylthio, phenylcarbonyl,
phenylsulfonyl,
where each of the 6 last-mentioned radicals is unsubstituted or substituted by
one or
more radicals selected from the group consisting of halogen, (C1-C4)alkyl,
(C~-C4)haloalkyl, (C~-C4)alkoxy, (C~-C4)haloalkoxy, (C~-C4)alkoxy-(C~-C4)alkyl
and
(C~-C4)alkoxy-(C~-C4)alkoxy,
preferably H, CHO, CO-CH3, CO-C6H5, S02CH3 or S02C2H5,
or
Ra and Rb together are (C~-C4)alkylidene, which is unsubstituted or
substituted by one
or more radicals selected from the group consisting of halogen, cyano, (C~-
C2)alkoxy,
(C~-C2)haloalkoxy and (C~-C2)alkylthio, or
NRaRb together are a saturated heterocyclyl radical having 5 or 6 ring atoms
which, in
addition to the nitrogen atom as hetero ring atom, optionally contains 1 to 3
further
hetero ring atoms selected from the group consisting of N, O and S, where the
heterocycle is unsubstituted or substituted by one or more radicals selected
from the
CA 02386800 2002-04-05
18
group consisting of (C~-C4)alkyl, (C~-C4)haloalkyl, (C~-C4)alkoxy and
(C~-C4)haloalkoxy, (C~-C4)alkoxy-(C~-C4)alkyl and (C~-C4)alkoxy-(C~-C4)alkoxy,
preferably (C~-C4)alkyl and (C1-C4)alkoxy.
Of interest are, for example, also compounds of the formula (I) according to
the
invention and salts thereof in which
R1 is (C~-Cg)alkyl, which is unsubstituted or substituted by one or more
radicals
selected from the group consisting of halogen, hydroxyl, cyano, nitro,
thiocyanato, formyl or else amino, (C1-C4)alkoxy, (C~-C4)haloalkoxy or else
N-mono(C~-C4)alkylamino or else N,N-di(C1-C4)alkylamino or (C~-C4)alkylthio,
(C~-C4)alkylsulfonyl, (C~-C4)haloalkylsulfonyl, [(C~-C4)alkyl]carbonyl,
[(C~-C4)haloalkyl]carbonyl, [(C~-C4)alkoxy]carbonyl, (C3-C9)cycloalkyl, phenyl
and heterocyclyl, where each of the 3 last-mentioned radicals is unsubstituted
or substituted, preferably unsubstituted or substituted by one or more
radicals
selected from the group consisting of halogen, cyano, hydroxyl, (C~-C4)alkyl,
(C1-C4)haloalkyl, (C~-C4)alkoxy, (C1-C4)haloalkoxy and (C~-C4)alkylthio, and
where heterocyclyl in each case preferably contains 3 to 9 ring atoms, 1 to 4
of
which are hetero ring atoms selected from the group consisting of N, O and S,
or
is [(C1-Cg)alkyl)carbonyl, [(C~-Cg)alkoxy]carbonyl or (C~-C4)alkylsulfonyl,
where
each of the 3 last-mentioned radicals is unsubstituted or substituted,
preferably
unsubstituted or substituted by one or more radicals selected from the group
consisting of halogen, (C~-C4)alkoxy, (C~-C4)haloalkoxy and (C~-C4)alkylthio,
or
is (C3-Cg)cycloalkyl, which is unsubstituted or substituted, preferably
unsubstituted or substituted by one or more radicals selected from the group
consisting of halogen, (C1-C4)alkyl, (Ct-C4)haloalkyl, (C1-C4)alkoxy,
(C~-C4)haloalkoxy and (C~-C4)alkylthio.
CA 02386800 2002-04-05
19
Preference is given to compounds of the formula (I) according to the invention
or salts
thereof in which R~ is (C~-C4)alkyl, such as, for example, methyl, ethyl, n-
propyl and
isopropyl, or (C~-C4)haloalkyl, such as, for example, 1-fluoroisopropyl, 1-
fluoroethyl,
1-fluoropropyl, CF3 and CCI3, or cyclopropyl, cyclobutyl, cyciopentyt,
cyclohexyl,
1-methylcyclopropyi, 1-methylcyclobutyl, 1-methylcyclopentyl, 1-
methylcyclohexyl or
benzyl.
Of interest are, for example, also compounds of the formula (I) according to
the
invention or salts thereof in which
~~ 10 R2 is H or formyl, (Ct-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C~-
C4)alkylsulfinyl,
(Ct-C4)alkylsulfonyl, (C~-C4)alkoxy, [(C~-C4)alkyl]carbonyl,
[(Ct-C4)alkoxy]carbonyl, where each of the 8 last-mentioned radicals is
unsubstituted or substituted, preferably unsubstituted or substituted by one
or
more radicals selected from the group consisting of halogen, (C1-C4)alkoxy and
(Ct-C4)haloalkoxy, or
(C3-Cg)cycloalkyt, (C3-Cg)cycloalkoxy, phenyl, phenoxy, phenylcarbonyl,
phenylsulfonyl, heterocyclyi, heterocyclyloxy, heterocyclylcarbonyl or
heterocyclylsulfonyl, where each of the 10 last-mentioned radicals is
unsubstituted or substituted and heterocyclyl in the 3 last-mentioned radicals
in
each case preferably contains 3 to 9 ring atoms, 1 to 4 of which are hetero
ring
atoms selected from the group consisting of N, O and S,
where preferably each of the 10 radicals mentioned is unsubstituted or
substituted by one or more radicals selected from the group consisting of
halogen, cyano, (C~-C4)alkyl, (C~-C4)haloalkyl, (C~-C4)alkoxy and
(C~-C4)haloalkoxy, or
is a group of the formula NR°Rd, where R~ and Rd, independently of one
another, are H, formyl, (C~-C4)alkyl, (C~-C4)alkylsulfonyl, (C~-C4)alkoxy,
[(C1-C4)aikyl]carbonyl or [(C~-C4)alkoxyJcarbonyl, where each of the 5 last-
mentioned groups is unsubstituted or substituted, preferably unsubstituted or
CA 02386800 2002-04-05
substituted by one or more radicals selected from the group consisting of
halogen, (C~-C4)alkoxy, (C~-C4)haloalkoxy and (C~-C4)alkoxy-(C~-C4)alkoxy,
or R° and Rd together are straight-chain (C2-C5)alkylene, which is
unsubstituted
or substituted by one or more radicals selected from the group consisting of
5 (C~-C4)alkyl, (C~-C4)alkoxy, (C~-C4)alkoxy-(C~-C4)alkyl and oxo.
Preference is given to compounds of the formula (I) according to the invention
or salts
thereof in which R2 is hydrogen, formyl, (C~-C4)alkyl, (C~-C4)haloalkyl,
(C~-C4)alkylsulfonyl, (C~-C4)haloalkylsulfonyl, (C~-C4)alkoxy, (C1-
Cq.)haloalkoxy,
10 [(C~-C4)alkyl]carbonyl, [(C~-C4)haloalkyl]carbonyl, [(C1-
C4)alkoxy]carbonyl,
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, phenylcarbonyl or
phenylsulfonyl.
Of interest are, for example, also compounds of the formula (I) according to
the
15 invention or salts thereof in which
R3 is halogen, CN, N02, SCN or a radical of the formula -X~-A1, where
X~ is a direct bond or a divalent group of the formula -O-, -S(O)p-, -S(O)p-O-
,
-O-S(O)p-, -CO-, -O-CO-, -CO-O-, -S-CO-, -CO-S-, -S-CS-, -CS-S-,
-O-CO-O-, -N R~ -, -O-N R~-, -N R~-O-, -N R~-CO-, -CO-N R~-,
20 -O-CO-NR~- or -NR~-CO-O-, preferably -O-, -S(O)p-, -CO-, -O-CO-,
-CO-O-, -S-CO-, -CO-S-, -NR~ -, -O-NR~-, -NR~-O-, -NR~-CO-,
-CO-NR~-, -O-CO-NR~- or -NR~-CO-O-, in which in each case p is the
integer 0, 1 or 2 and R~ is hydrogen, (C~-Cq.)alkyl, (C2-C4)alkenyl,
(C2-C4)alkynyl, phenyl, phenyl-(C~-CZ)alkyl, (C3-Cg)cycloalkyl or
[(C~-C4)alkyl]carbonyl, and
A~ is hydrogen, (C~-Cg)alkyl, (C2-Cg)alkenyl, (C2-Cg)alkynyl,
(C3-Cg)cycloalkyl, phenyl or heterocyclyl having 3 to 9 ring atoms and 1
to 3 hetero ring atoms selected from the group consisting of N, O and S,
where each of the 6 last-mentioned radicals is unsubstituted or
CA 02386800 2002-04-05
21
substituted, preferably unsubstituted or substituted by one or more
radicals selected from the group consisting of halogen, cyano,
(C~-C4)alkyl, (C3-Cg)cycloalkyl, (C~-C4)alkoxy, (C~-C4)haloalkoxy,
(C~-C4)alkylthio and, in the case of cyclic radicals, also (C~-C4)haloalkyl
and (C~-C4)alkoxy-(C~-C4)alkyl and, including substituents, has
preferably up to 16 carbon atoms.
Preference is given to compounds (I) and salts thereof in which
R3 is H, (C~-C4)alkyl, preferably methyl or ethyl, or cyclopropyl, cyclobutyl,
,~ 10 cyclopentyl, cyclohexyl or phenyl, where each of the 8 last-mentioned
radicals is
unsubstituted or substituted by one or more radicals selected from the group
consisting of halogen and (C~-C2)alkoxy and, in the case of cyclic radicals,
also
(C~-C2)alkyl, (C~-C2)haloalkyl and (C~-C4)alkoxy-(C~-C4)alkyl.
Of interest are, for example, also compounds of the formula (I) according to
the
invention or salts thereof in which
each of the radicals R4, R5, R6, R' and R8, independently of one another, is
halogen,
nitro, cyano, thiocyanato or a radical of the formula -X2-A2, where
X2 is a direct bond or a divalent group of the formula -O-, -S(O)q-, -S(O)q-O-
,
-O-S(O)q-, -S(O)q-NR'-, -NR'-S(O)q-, -CO-, -O-CO-, -CO-O-, -S-CO-,
-CO-S-, -S-CS-, -CS-S-, -O-CO-O-, -NR' -, -O-NR'-, -NR'-O-, -NR'-CO-,
-CO-NR'-, -O-CO-NR'- or -NR'-CO-O-, preferably -O-, -S(O)q-, -S(O)q-O-,
-S(O)q-NR'-, -NR'-S(O)q-, -CO-, -O-CO-, -CO-O-, -S-CO-, -CO-S-, -NR' -,
-O-NR'-, -NR'-O-, -NR'-CO-, -CO-NR'-, -O-CO-NR'- or -NR'-CO-O-, in
which in each case q is the integer 0, 1 or 2 and Rr, independently of one
another, is in each case hydrogen, amino, mono- or di(C~-C4)alkylamino,
mono- or di(C~-C4)arylamino, N-(C~-C4)alkyl-N-arylamino, (C~-C4)alkyl,
(C2-C4)alkenyl, (C2-C4)alkynyl, phenyl, phenyl(C~-C4)alkyl,
CA 02386800 2002-04-05
22
phenylcarbonyl, (C3-Cg)cycloalkyl, {C5-C6)cycloalkenyl,
[(Ct-C4)alkyl]carbonyl, (C~-C4)alkylsulfonyl, (C1-C4)alkylsulfinyl,
phenylsulfonyl or phenylsulfinyl, where each of the 18 last-mentioned
radicals is unsubstituted or substituted, preferably unsubstituted or
substituted by one or more radicals selected from the group consisting of
halogen, cyano, (C1-C4)alkyl, (C~-C4)alkoxy, (C~-C4)haloalkoxy and, in
the case of cyclic radicals, also (C1-C4)haloalkyl and (C1-C4)alkoxy-
(C~-C4)alkyl, and
,~.,. A2 is hydrogen, (C1-Cg)alkyl, (C2-Cg)alkenyl, (C2-Cg)alkynyl,
(Cg-Cg)cycloalkyl, (C5-Cg)cycloalkenyl, phenyl or heterocyclyl having 3 to
6 ring atoms and 1 to 3 hetero ring atoms selected from the group
consisting of N, O and S, where each of the 7 last-mentioned radicals are
unsubstituted or substituted, preferably unsubstituted or substituted by
one or more radicals selected from the group consisting of halogen,
cyano, hydroxyl, amino or else mercapto or aminocarbonyl, mono- and
di(C1-C4)alkylamino, mono- and diphenylamino, N-(C1-C4)alkyl-N-
phenylamino, mono- and di[(C~-C4)alkanoyl]amino, mono- and di-
[(C1-C4)alkylsulfonyl]amino, N-{C~-C4)alkyl-N-[(C1-C4)alkanoyl]amino,
°"~ (C~-C4)alkyl-N-[(C~-C4)alkylsulfonyl]amino, N-phenyl-N-
[(C~-C4)alkanoyl]amino, N-phenyl-N-[(C~-C4)alkylsulfonyl]amino,
(C~-C4)alkoxy, (C1-C4)alkylthio, (C~-C4)alkylsulfonyl,
(C~-C4)alkylsulfinyl, [(C1-C4)alkyl]carbonyl, [(C~-C4)alkoxy]carbonyl,
[(C1-C4)alkyl]carbonyloxy, (Cg-Cg)cycloalkyl, (Cg-Cg)cycloalkoxy,
(Cg-Cg)cycloalkylcarbonyl, (Cg-Cg)cycloalkylcarbonyloxy, phenyl,
phenoxy, phenylthio, phenylcarbonyl, phenylcarbonyloxy, heterocyclyl,
heterocyclyloxy, heterocyclylthio, heterocyclylcarbonyl,
heterocyclylcarbonyloxy and, in the case of cyclic radicals, also
(C1-Cg)alkyl,
CA 02386800 2002-04-05
23
where each of the 35 last-mentioned radicals is unsubstituted or
substituted, preferably unsubstituted or substituted by one or more
of the radicals selected from the group consisting of halogen,
cyano, hydroxyl, amino, mono- and di(C~-C4)alkylamino, mono-
and di-phenylamino, N-(C~-C4)alkyl-N-phenylamino,
(C~-C4)alkoxy, (C~-C4)alkylthio, (C3-Cg)cycloalkyl,
(C3-C6)cycloalkoxy, phenyl, phenoxy and phenylthio and, in the
case of cyclic radicals, also (C~-C4)alkyl, (C~-C4)haloalkyl and
(C~-C4)alkoxy-(Ct-C4)alkyl,
and A2, including substituents, has preferably up to 16 carbon atoms,
or
two adjacent radicals from the group consisting of R4, R5, R6, R' and R8
together with the carbon atoms of the phenyl ring to which they are attached
form a fused ring having 4 to 6 ring atoms which is carbocyclic or contains 1
to
3 hetero ring atoms selected from the group consisting of N, O and S and which
is unsubstituted or substituted by one or more radicals selected from the
group
consisting of halogen, (C~-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl,
[(C1-C4)alkyl]carbonyl, (C~-Cs)alkoxy, [(C1-C4)alkoxy]carbonyl,
'°'~ (C~-C4)alkylsulfonyl and (C~-C4)alkylsulfinyl,
where at least two radicals, preferably 2 or 3 radicals, in particular 2
radicals, from the
group consisting of R4, R5, R6, R' and R8 are different from hydrogen.
Preference is also given, for example, to compounds of the formula (I)
according to the
invention or salts thereof in which
each of the radicals R4, R5, R6, R' and R8, independently of one another, is
hydrogen,
halogen, hydroxyl, amino, vitro, formyl, aminocarbonyl, carboxyl, cyano,
thiocyanato or
else aminosulfonyl or (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylthio,
(C1-C4)alkylsulfonyl, (C1-C4)alkylsulfinyl, (C2-C6)alkenyl, (C2-C6)alkynyl,
CA 02386800 2002-04-05
24
(C1-Cg)alkylcarbonyl, (C1-Cg)alkoxycarbonyl, (C1-Cg)alkylcarbonyloxy, mono- or
di-
[(C1-C4)alkyl]amino, mono- and diphenylamino, N-(C1-C4)alkyl-N-phenylamino or
else
mono- or di[(C1-C4)alkyl]aminosulfonyl, mono- or di[(C1-Cg)alkanoyl]amino,
N-[(C1-Cg)alkanoyl]-N-[(C1-C4)alkyl]amino, N-phenyl-N-[(C~-C4)alkanoyl]amino,
mono- or di[(C1-Cg)alkylsulfonyl]amino, N-[(C1-Cg)alkylsulfonyl]-N-
[(C1-C4)alkyl]amino, N-phenyl-N-[(C~-C4)alkylsulfonyl]amino,
where each of the 24 last-mentioned radicals is substituted by one or more
radicals selected from the group consisting of halogen, vitro, amino, mono-
and di[(C1-C4)alkyl]amino, mono- and diphenylamino, N-(C1-C4)alkyl-N-
phenylamino, hydroxyl, cyano, (C1-C4)alkoxy or else mercapto or
(C1-C4)alkylthio, (C1-C4)haloalkoxy, (C1-C4)alkylcarbonyl, (C1-
C4)alkoxycarbonyl, (C3-Cg)cycloalkyl, (C3-Cg)cycloalkylcarbonyl,
(C3-Cg)cycloalkylcarbonyloxy, phenyl, phenoxy, phenylthio, phenylcarbonyl,
phenoxycarbonyl, phenylcarbonyloxy, phenylsulfonyl, where the 7 last-
mentioned radicals are unsubstituted or optionally substituted in the phenyl
radical,
or
is (C3-Cg)cycloalkyl, (C3-Cg)cycloalkoxy, (C3-Cg)cycloalkylcarbonyl, phenyl,
phenoxy,
phenylthio, phenylcarbonyl, phenoxycarbonyl, phenylcarbonyloxy or
phenylsulfonyl,
heterocyclyl, heterocyclyloxy, heterocyclylthio, heterocyclylcarbonyl,
heterocyclylcarbonyloxy, where each of the 14 last-mentioned radicals is
unsubstituted
or substituted by one or more radicals selected from the group consisting of
halogen,
vitro, amino, (C1-C4)alkyl, mono- and di{(C1-C4)alkyl]amino, mono- and di-
phenylamino, N-(C1-C4)alkyl-N-phenylamino, hydroxyl, cyano, (C1-C4)alkoxy,
(C1-C4)alkylthio, (C1-C4)haloalkoxy, (C1-C4)alkylcarbonyl, (C1-
C4)alkoxycarbonyl.
Preference is also given, for example, to compounds of the formula (I)
according to the
invention or salts thereof in which each of the radicals R4, R5, R6, R' and
R8,
independently of one another, is
(C1-Cg)alkoxy-(C1-Cg)alkyl, (C1-Cg)alkylthio-(C1-C6)alkyl, aminocarbonyl-(C1-
CA 02386800 2002-04-05
C4)alkyl, amino-(C1-C4)alkyl, mono- and di[(C1-C4)alkyl]amino-(C1-C4)alkyl,
(C3-Cg)-
cycloalkyl-(C1-C4)alkyl, (C3-Cg)-cycloalkyl-(C1-C4)alkenyl, (C3-Cg)cycloalkyl-
(C1-
C4)alkynyl, (C1-C6)alkylcarbonyl-(C1-Cg)alkyl, (C1-Cg)alkoxycarbonyl-(C1-
Cg)alkyl,
(C1-Cg)alkylcarbonyloxy-(C 1-Cg)-alkyl, (C1-Cg)cycloalkoxy-(C 1-Cq,)alkyl, (C3-
5 Cg)cycloalkylcarbonyl-(C1-C4)alkyl, (C1-Cg)alkoxycarbonyl-(C1-Cg)alkyl, (C1-
Cg)alkyicarbonyioxy-(C1-Cg)-alkyl, (C1-Cg)cycloalkoxy-(C1-C4)alkyl, (C3-
Cg)cycloalkylcarbonyl-(C1-C4)alkyl, mono- or di(C1-Cg)alkanoylamino-(C1-
C4)alkyl,
mono- and di[(C1-C4)alkylsulfonyl]amino-(C1-C,~)alkyl, N-(Ct-C4)alkyl-N-
[(C1-C4)alkanoyl]amino-(C1-C4)alkyl, (C~-C4)alkyl-N-[(C~-
C4)alkylsulfonyl]amino-
10 (C1-C4)alkyl, N-phenyl-N-[(C~-C4)aikanoyl]amino-(C1-C4)alkyl, N-phenyl-N-
[(Ct-C4)alkylsulfonyl]amino-(C1-C4)alkyl, phenoxy-(C1-Cg)-alkyl,
phenylcarbonyl-(C1-
Cg)aikyl, phenyloxycarbonyl-(C1-Cg)aikyl, phenylcarbonyloxy(C1-C4)alkyl,
phenyl(C1-
Cg)alkyl, phenyl(C1-Cg)alkenyl, phenyl-(C1-Cg)alkynyl, heterocyclyl(C1-
Cg)alkyl,
heterocyclyloxy(C1-Cg)alkyl, heterocyclylthio(C1-Cg}alkyl,
heterocyclylsulfonyl(C1-
15 Cg)alkyl, heterocyclylamino(C1-Cg)alkyl or one of the 38 last-mentioned
radicals which
is substituted by one or more radicals selected from the group consisting of
halogen,
hydroxyl, vitro, cyano, (C1-Cg)alkyl, (C1-Cg}alkoxy, (C1-Cg)alkylthio, (C1-
C4)alkylsulfonyl, (C1-Cg)haloalkyl and (C1-Cg)haloalkoxy.
20 Furthermore preferably, each of the radicals R4, R5, R6, R' and R8,
independently of
one another, is hydrogen, halogen, hydroxyl, amino, vitro, formyl, carboxyl,
cyano,
(C1-Cg)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkyl, halo(C1-C4)alkoxy, hydroxy(C1-
C4)alkyl, hydroxy(G1-C4)alkoxy, (C1-C4)alkoxy-(C1-C4)alkyl, halo(C1-C,~)alkoxy-
(C1-
C4)alkyl, halo(C1-C4)aikoxy-(C1-Cq,)alkoxy, (C1-C4)alkoxy-(C1-C4)alkoxy,
25 (C3-Cg)cycloalkyl, halo(C3-Cg)cycloalkyl, (C2-C4)alkenyl, halo(C2-
C4)alkenyl,
(C2-C4)alkynyl, halo(C2-C4)alkynyl, (C1-C4)alkylcarbonyl, (C1-
C4)alkoxycarbonyl or
else (C1-C4)alkylsulfonyl or else (C1-C~)alkylsulfinyf or else (C1-
C4)alkylaminosulfonyl or else di[(C1-C4)alkyl]aminosulfonyl or (C1-
C4)alkylcarbonyl-
CA 02386800 2002-04-05
26
(C1-C4)alkyl, (C1-C4)alkylcarbonyloxy, (C1-C4)alkylthio(C1-C4)alkyl,
mercapto(C1-
C4)alkyl, amino(C1-C4)alkyl, (C1-Cq,)alkylamino, (C1-C4)alkylamino-(C1-
C4)alkyl,
di[(C1-Cq,)-alkyl]amino, di((C1-C4)-alkyl]amino-(C1-C4)alkyl, (C1-
C4)alkanoylamino,
(C1-C4)alkylsulfonylamino, di[(C1-C4)alkanoyl]amino, di[(C1-
C4)alkylsulfonyl]amino or
phenyl, phenoxy, phenylcarbonyl, phenoxycarbonyl, phenylcarbonyloxy,
phenoxy(C1-
C4)alkyl, phenylcarbonyl(C1-C4)alkyl, phenyl(C1-C4)alkyl or one of the 8 last-
mentioned radicals which is substituted in the phenyl moiety by one or more
radicals
selected from the group consisting of halogen, (C1-C4)alkyl, (C1-C4)alkoxy,
(C1-C4)haloalkyl and (C1-C4)haloalkoxy and also hydroxyl.
X10
Furthermore preferably, each of the radicals R4, R5, R6, R' and R8,
independently of
one another, is hydrogen, hydroxyl, amino, nitro, formyl, carboxyl, cyano,
fluorine,
chlorine, bromine, iodine, methyl, ethyl, n-propyl, isopropyl, n-butyl,
isobutyl, t-butyl,
sec-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, CF3, CHF2, CH2F, CCIg,
OCHF2,
OCFg, OCH2F, CH2NH2, CH2CH2NH2, CH20H, CH2CH20H, CH2SH, CH2CH2SH,
OCH2CH20H, OCH(CH3)OH, CH20CH3, CH20C2H5, CH2CH20CH3,
CH2CH20C2H5, OCH20CH3, OCH20C2H5, OCH2CH20CHg, OCH2CH20C2H5,
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-fluorocyclopropyl, vinyl,
allyl, prop-1-
enyl, 1-methyl-prop-1-enyl, 1-ethyl-prop-1-enyl, but-1-enyl, but-2-en-1-yl,
but-3-en-1-yl,
z0 ethynyl, propargyl, prop-1-yn-1-yl, but-1-yn-1-yl, but-2-yn-1-yl, but-3-yn-
1-yl, 1-methyl-
prop-1-yn-1-yl, acetyl, propionyl, propylcarbonyl, methylsulfonyl,
ethylsulfonyl,
methylsulfinyl, ethylsulfinyl, aminosulfonyl, methylaminosulfonyl,
ethylaminosulfonyl;
propylaminosulfonyl, isopropylaminosulfonyl, dimethylaminosulfonyl,
diethylaminosulfonyl, methoxycarbonyl, ethoxycarbonyl, methoxycarbonyloxy,
ethoxycarbonyloxy, methoxycarbonylmethyl, ethoxycarbonylmethyl,
methoxycarbonyloxymethyl, ethoxycarbonyloxymethyl, methylthio, ethylthio,
propylthio,
methylthiomethyl, ethylthiomethyl, methylthioethyl, ethylthioethyl,
methylamino,
ethylamino, propylamino, isopropylamino, dimethylamino, diethylamino,
methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, diethylaminoethyl,
formylamino, acetylamino, formylaminomethyl, formylaminoethyl,
methylsulfonylamino,
ethylsulfonylamino, dimethylsulfonylamino, diethylsulfonylamino,
CA 02386800 2002-04-05
27
methylsulfonylaminomethyl, ethylsulfonylaminomethyl,
dimethylsulfonylaminomethyl,
diethylsulfonylaminomethyl, phenyl, phenoxy, phenylcarbonyl, phenoxycarbonyl,
phenylcarbonyloxy, phenoxymethyl, phenoxyethyl, phenylcarbonylmethyl,
phenylcarbonylethyl, phenylmethyl (benzyl), phenylethyl (phenethyl) or one of
the 11
last-mentioned radicals which is substituted in the phenyl moiety by one or
more
radicals selected from the group consisting of halogen, (C1-C4)alkyl, (C1-
C4)alkoxy,
(C1-C4)haloalkyl, (C1-C4)haloalkoxy and hydroxyl.
Of particular interest are compounds of the formula (I) and salts thereof in
which
R~ is methyl which is unsubstituted or substituted as mentioned above.
Of particular interest are also compounds of the formula (I) according to the
invention
and salts thereof in which R~ is (C~-C~p)alkyl which is unsubstituted or
substituted by
substituents according to the invention other than halogen.
Of particular interest are also compounds of the formula (I) according to the
invention
and salts thereof in which R~ is different from unsubstituted or substituted
(Ct-C~ p)alkyl.
Of particular interest are also compounds of the formula (I) according to the
invention
and salts thereof in which R5, R6, R~ and R8 are each different from (C1-
C~p)alkyl or
(C~ -C~ p)alkoxy.
Of particular interest are also compounds of the formula (I) according to the
invention
and salts thereof in which R3 is different from methyl, i.e., for example, (C2-
C1p)alkyl,
which is unsubstituted, or (C~-C~p)alkyl, which is substituted, or one of the
other
definitions according to the invention of R3.
The present invention also provides processes for preparing the compounds of
the
formula (I) or salts thereof, which comprise
CA 02386800 2002-04-05
28
a) reacting a compound of the formula (II),
R~ - Fu (II)
in which Fu is a functional group selected from the group consisting of the
carboxylic esters, carboxylic orthoesters, carbonyl chlorides, carboxamides,
carboxylic anhydrides and trichloromethyl with a biguanide of the formula
(III) or
an acid addition salt thereof
NH NH R3 R4
A~N~N ~ R5 (111)
H
R2 8 ~ / 6
R Y 'R
R7
or
b) reacting a compound of the formula (IV),
R1
N_ \ N
,~~, (IV)
~N~Z~
A
in which Z~ is an exchangeable radical or a leaving group, for example
chlorine,
trichloromethyl, (C~-C4)alkylsulfonyl and unsubstituted or substituted phenyl-
24 (C~-C4)alkylsulfonyl or (C~-C4)alkylphenylsulfonyl, with a suitable amine
of the
formula (V) or an acid addition salt thereof
CA 02386800 2002-04-05
29
R4
RJ (V)
2
R Q ~ ~ Q6
R~
where in the formulae (II), (III), (IV) and (V) the radicals Rt, R2, R3, R4,
R5, R6, R', R8
and A are as defined in formula (I).
The compounds of the formula (II) and (III) are preferably reacted base-
catalyzed in an
inert organic solvent, such as, for example, tetrahydrofuran (THF), dioxane,
acetonitrile, dimethylformamide (DMF), methanol and ethanol, at temperatures
between -10°C and the boiling point of the solvent, preferably at from
20°C to 60°C; if
acid addition salts of the formula (III) are used, these are generally
liberated in situ
with the aid of a base. Suitable bases or basic catalysts are alkali metal
hydroxides,
alkali metal hydrides, alkali metal carbonates, alkali metal alkoxides,
alkaline earth
metal hydroxides, alkaline earth metal hydrides, alkaline earth metal
carbonates or
organic bases, such as triethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU).
The base in question is employed, for example, in the range from 0.1 to 3
molar
equivalents, based on the compound of the formula (III). Based on the compound
of
the formula (III), the compound of the formula (II) can be employed, for
example, in
'~ equimolar amounts or in an excess of up to 2 molar equivalents. In
principle, the
corresponding processes are known from the literature (compare: Comprehensive
Heterocyclic Chemistry, A.R. Katritzky, C.W. Rees, Pergamon Press, Oxford, New
York, 1984, Vol.3; Part 2B; ISBN 0-08-030703-5, p.290).
The compounds of the formulae (IV) and (V) are preferably reacted base-
catalyzed in
an inert organic solvent, such as, for example, THF, dioxane, acetonitrile,
DMF,
methanol and ethanol, at temperatures between -10°C and the boiling
point of the
solvent or solvent mixture in question, preferably at from 20°C to
60°C, in particular at
from 30°C to 80°C, where the compound (V), if it is employed as
acid addition salt, is,
if appropriate, liberated in situ using a base. Suitable bases or basic
catalysts are
alkali metal hydroxides, alkali metal hydrides, alkali metal carbonates,
alkali metal
CA 02386800 2002-04-05
alkoxides, alkaline earth metal hydroxides, alkaline earth metal hydrides,
alkaline earth
metal carbonates or organic bases such as triethylamine or 1,8-diaza-
bicyclo[5.4.0]undec-7-ene (DBU). The base in question is generally employed in
the
range from 1 to 3 molar equivalents, based on the compound of the formula
(IV), and
5 the compound of the formula (IV) can be employed, for example, in equimolar
amounts or in an excess of up to 2 molar equivalents, based on the compound of
the
formula (V). In principle, the corresponding processes are known from the
literature (cf.
Comprehensive Heterocyclic Chemistry, A.R. Katritzky, C.W. Rees, Pergamon
Press,
Oxford, New York, 1984, Vol.3; Part 2B; ISBN 0-08-030703-5, p. 482).
,,~,.. The starting materials of the formulae (II), (III), (IV) and (V) are
either commercially
available, or they can be prepared by or analogously to processes known from
the
literature. Some of the compounds of the formulae (III) are novel, and they
also form
part of the subject matter of the invention. The compounds can also be
prepared, for
example, by one of the processes described below.
The compound of the formula (IV), or a direct precursor thereof, can be
prepared, for
example, as follows:
1. Reaction of a compound of the formula (II) with an amidinothiourea
derivative of
the formula (VI),
NH
~ Z 2 (VI)
N~S~
H
in which Z2 is (C~-C4)alkyl or phenyl(C~-C4)alkyl and A is as defined in
formula
(I) gives compounds of the formula (IV) in which Z1 - -SZ2.
2. Reaction of amidine of the formula (VII) or an acid addition salt thereof
H2N-CRS=NH (VII)
CA 02386800 2002-04-05
' 31
in which R1 is as defined in formula (I)
with a N-cyanodithioiminocarbonate of the formula (VIII),
NC-N=C(S-Z3)2 (VIII)
in which Z3 is (C~-C4)alkyl or phenyl(C~-C4)alkyl gives compounds of the
formula (IV) in which Z~ - -S-Z3.
3. Reaction of an alkali metal dicyanamide with a carboxylic acid derivative
of the
"~10 formula (II) mentioned gives compounds of the formula (IV) in which Z~ =
NH2,
4. Reaction of trichloroacetonitrile with a nitrite of the formula (IX),
R1 - CN (IX)
in which R~ is as defined in formula (I) initially gives compounds of the
formula
(X),
R~
N_ \ N X
( )
Z~N~Z~
in which Z~ and Z4 are each CCI3 which, by subsequent reaction with
compounds of the formula H-A (A is as defined in formula (I)), gives compounds
of the formula (IV) in which Z1 = CCIg.
The substituted phenyl alkyl amines of the formula (V) required as starting
materials
are known and/or can be prepared by processes known per se. For example, the
corresponding aromatic ketone can be reductively aminated directly to the
amine, for
example by reaction with sodium cyanoborohydride and ammonium acetate or with
a
CA 02386800 2002-04-05
32
mixture of ammonium formate and formic acid followed by cleavage of the amide,
or
the ketone is converted into an advantageous derivative, for example an oxime,
which
is then reduced to the amine (cf. JP 11035536; JP 11043470; J. Am. Chem. Soc.
1983, 105, 1578; Synthesis 1980, 695).
The reaction of the carboxylic acid derivatives of the formula (II) with the
amidinothiourea derivatives of the formula (VI) is preferably carried out base-
catalyzed
in an organic solvent, such as, for example, acetone, THF, dioxane,
acetonitrile, DMF,
methanol, ethanol, at temperatures from -10°C to the boiling point of
the solvent,
preferably at from 0°C to 20°C. However, the reaction can also
be carried out in water
,,.,. or in aqueous solvent mixtures with one or more of the abovementioned
organic
solvents. If (VI) is employed as acid addition salt, it can, if appropriate,
be liberated in
situ using a base. Suitable bases or basic catalysts are alkali metal
hydroxides, alkali
metal hydrides, alkali metal carbonates, alkali metal alkoxides, alkaline
earth metal
hydroxides, alkaline earth metal hydrides, alkaline earth metal carbonates or
organic
bases, such as triethylamine or 1,8-diazabicyclo[5.4.OJundec-7-ene (DBU). The
base
in question is, for example, employed in the range from 1 to 3 molar
equivalents,
based on the compound of the formula (VI). Compounds of the formula (II) and
(VI)
can be employed, for example, in equimolar amounts, or with an excess of up to
2
molar equivalents of the compound of the formula (II). In principle, the
corresponding
processes are known from the literature (compare: H. Eilingsfeld, H.
Scheuermann,
Chem. Ber.; 1967, 100, 1874); the corresponding intermediates of the formula
(IV) are
novel.
The reaction of the amidines of the formula (VII) with the
N-cyanodithioiminocarbonates of the formula (VIII) is preferably carried out
base-
catalyzed in an inert organic solvent, such as, for example, acetonitrile,
DMF,
dimethylacetamide (DMA), N-methylpyrrolidone (NMP), methanol and ethanol, at
temperatures from -10°C to the boiling point of the solvent, preferably
at from 20°C to
80°C. If (VII) is employed as acid addition salt, it can, if
appropriate, be liberated in situ
using a base. Suitable bases or basic catalysts are alkali metal hydroxides,
alkali metal
hydrides, alkali metal carbonates, alkali metal alkoxides, alkaline earth
metal
hydroxides, alkaline earth metal hydrides, alkaline earth metal carbonates or
organic
bases, such as triethylamine or 1,8-diazabicyclo[5.4.OJundec-7-ene (DBU). The
base
CA 02386800 2002-04-05
33
in question is employed, for example, in the range from 1 to 3 molar
equivalents,
based on the compound of the formula (VIII), and compounds of the formulae
(VII) and
(VIII) can generally be employed in equimolar amounts or with an excess of two
molar
equivalents of the compound of the formula (II). In principle, the
corresponding
processes are known from the literature (compare: T.A. Riley, W.J. Henney,
N.K.
Dalley, B.E. Wilson, R.K. Robins; J. Heterocyclic Chem.; 1986, 23 (6), 1706-
1714); the
corresponding intermediates of the formula (IV) are novel.
Intermediates of the formula (X) where Z1 = chlorine can be prepared by
reacting alkali
metal dicyanamide with a carboxylic acid derivative of the formula (II), Fu
then
'"'"~"" preferably being the functional group carbonyl chloride or
carboxamide. The reaction
of the reaction components is carried out, for example, acid-catalyzed in an
inert
organic solvent, such as, for example, toluene, chlorobenzene, chlorinated
hydrocarbons, at temperatures between -10°C and the boiling point of
the solvent,
preferably at from 20°C to 80°C, where the intermediates formed
can be chlorinated in
situ using a suitable chlorinating agent, such as, for example, phosphorus
oxychloride.
Suitable acids are, for example, hydrohalic acids, such as HCI, or else Lewis
acids,
such as, for example, AICI3 or BF3 (compare US-A-5095113, DuPont).
Intermediates of the formula (X) where Z1, Z4 = trihalomethyl can be prepared
by
reacting the corresponding trihaloacetonitriles with a carbonitrile of the
formula (IX).
The reaction of the reaction components is carried out, for example, acid-
catalyzed in
an inert organic solvent, such as, for example, toluene, chlorobenzene,
chlorinated
hydrocarbons, at temperatures between -40°C and the boiling point of
the solvent,
preferably at from -10°C to 30°C. Suitable acids are, for
example, hydrohalic acids,
such as HCI, or else Lewis acids, such as, for example, AICIg or BF3 (cf.
EP-A-130939, Ciba Geigy).
Intermediates of the formula (IV), in which Z~ _ (C~-C4)alkylmercapto or
unsubstituted
phenyl(C~-C4)alkylmercapto, can be converted in an inert organic solvent, such
as, for
example toluene, chlorobenzene, chlorinated hydrocarbons or others, at
temperatures
between -40°C and the boiling point of the solvent, preferably at from
20°C to 80°C,
with a suitable chlorinating agent, such as, for example elemental chlorine or
CA 02386800 2002-04-05
34
phosphorus oxychloride, into more reactive chlorotriazines of the formula
(IV), in which
Z~ = CI (cf. J.K. Chakrabarti, D.E. Tupper; Tetrahedron 1975, 31(16), 1879-
1882).
Intermediates of the formula (IV), in which Z~ _ (C~-C4)alkylmercapto or
unsubstituted
or substituted phenyl(C~-Cq,)alkylmercapto or (C1-C4)alkylphenylthio, can be
oxidized
in a suitable solvent, such as, for example, chlorinated hydrocarbons, acetic
acid,
water, alcohols, acetone or mixtures thereof at temperatures between
0°C and the
boiling point of the solvent, preferably at from 20°C to 80°C,
with a suitable oxidizing
agent, such as, for example, m-chloroperbenzoic acid, hydrogen peroxide,
potassium
x.10 peroxomonosulfate (compare: T.A. Riley, W.J. Henney, N.K. Dalley, B.E.
Wilson, R.K.
Robins; J. Heterocyclic Chem.; 1986, 23 (6), 1706-1714).
The following acids are suitable for preparing the acid addition salts of the
compounds
of the formula (I): hydrohalic acids, such as hydrochloric acid or hydrobromic
acid,
furthermore phosphoric acid, nitric acid, sulfuric acid, mono- or bifunctional
carboxylic
acids and hydroxycarboxylic acids, such as acetic acid, malefic acid, succinic
acid,
fumaric acid, tartaric acid, citric acid, salicylic acid, sorbic acid or
lactic acid, and also
sulfonic acids, such as p-toluenesulfonic acid and 1,5-naphthalenedisulfonic
acid. The
acid addition compounds of the formula (I) can be obtained in a simple manner
by the
customary methods for forming salts, for example by dissolving a compound of
the
formula (I) in a suitable organic solvent, such as, for example, methanol,
acetone,
methylene chloride or benzene, and adding the acid at temperatures from 0 to
100°C,
and they can be isolated in a known manner, for example by filtration, and, if
appropriate, purified by washing with an inert organic solvent.
The base addition salts of the compounds of the formula (I) are preferably
prepared in
inert polar solvents, such as, for example, water, methanol or acetone, at
temperatures
from 0 to 100°C. Examples of bases which are suitable for the
preparation of the salts
according to the invention are alkali metal carbonates, such as potassium
carbonate,
alkali metal hydroxides and alkaline earth metal hydroxides, for example NaOH
or
KOH, alkali metal hydrides and alkaline earth metal hydrides, for example NaH,
alkali
metal alkoxides and alkaline earth metal alkoxides, for example sodium
methoxide or
potassium tert-butoxide, or ammonia or ethanolamine.
CA 02386800 2002-04-05
Solvents referred to as "inert solvents" in the above process variants are to
be
understood as meaning in each case solvents which are inert under the reaction
conditions in question, but which need not be inert under all reaction
conditions.
5
A collection of compounds (I) which can be synthesized by the abovementioned
process may also be prepared in a parallel manner where the process may be
carried
out manually, partially automated or fully automated. In this case, it is
possible to
automate the procedure of the reaction, the work-up or the purification of the
products
10 or of the intermediates. In total, this is to be understood as meaning a
procedure as is
described, for example, by S. H. DeWitt in "Annual Reports in Combinatorial
Chemistry
and Molecular Diversity: Automated Synthesis", Volume 1, Verlag Escom, 1997,
pages
69 to 77.
15 A number of commercially available apparatuses as are offered by, for
example, Stem
Corporation, Woodrolfe Road, Tollesbury, Essex, CM9 8SE, England and H+P
t_abortechnik GmbH, Bruckmannring 28, 85764 Oberschlei(3heim, Germany may be
used for the parallel procedure of the reaction and work-up. For the parallel
purification
of compounds (I), or of intermediates obtained during the preparation, use may
be
20 made, inter alia, of chromatography apparatuses, for example those from
ISCO, Inc.,
4700 Superior Street, Lincoln, NE 68504, USA. The apparatuses mentioned lead
to a
modular procedure in which the individual process steps are automated, but
manual
operations have to be performed between the process steps. This can be avoided
by
employing semi-integrated or fully integrated automation systems where the
25 automation modules in question are operated by, for example, robots. Such
automation systems can be obtained, for example, from Zymark Corporation,
Zymark
Center, Hopkinton, MA 01748, USA.
In addition to the methods described here, compounds (I) may be prepared in
part or
30 fully by solid-phase-supported methods. For this purpose, individual
intermediate steps
or all intermediate steps of the synthesis or of a synthesis adapted to suit
the
procedure in question are bound to a synthetic resin. Solid-phase-supported
synthesis
methods are described extensively in the specialist literature, for example
Barry A.
Bunin in "The Combinatorial Index", Verlag Academic Press, 1998.
CA 02386800 2002-04-05
3s
The use of solid-phase-supported synthesis methods permits a series of
protocols
which are known from the literature and which, in turn, can be performed
manually or
in an automated manner. For example, the "tea-bag method" (Houghten, US
4,631,211; Houghten et al., Proc. Natl. Acad. Sci, 1985, 82, 5131-5135), in
which
products from IRORI, 11149 North Torrey Pines Road, La Jolla, CA 92037, USA,
are
employed, may be partially automated. The automation of solid-phase-supported
parallel synthesis is performed successfully, for example, by apparatuses from
Argonaut Technologies, Inc., 887 Industrial Road, San Carlos, CA 94070, USA or
MultiSynTech GmbH, Wullener Feld 4, 58454 Witten, Germany.
The preparation methods described here give compounds (I) in the form of
collections
of substances known as libraries. The present invention also relates to
libraries of the
compounds (I) which contain at least two compounds (I) and their
intermediates.
The compounds of the formula (I) according to the invention and their salts,
hereinbelow together referred to as compounds of the formula (I) (according to
the
invention), have excellent herbicidal activity against a broad spectrum of
economically
important monocotyledonous and dicotyledonous harmful plants. The active
compounds also act efficiently on perennial weeds which produce shoots from
rhizomes, root stocks or other perennial organs and which are difficult to
control. In this
context, it is generally immaterial whether the substances are applied pre-
sowing, pre-
emergence or post-emergence.
Specifically, examples may be mentioned of some representatives of the
monocotyledonous and dicotyledonous weed flora which can be controlled by the
compounds according to the invention, without these being a restriction to
certain
species.
Examples of weed species on which the active compounds act efficiently are,
from
amongst the monocotyledons, Avena, Lolium, Alopecurus, Phalaris, Echinochloa,
Digitaria, Setaria and also Cyperus species from the annual sector and, from
amongst
the perennial species, Agropyron, Cynodon, tmperata and Sorghum, and also
perennial Cyperus species.
In the case of the dicotyledonous weed species, the spectrum of act'ron
extends to
species such as, for example, Galium, Viola, Veronica, Lamium, Stellaria,
Amaranthus,
CA 02386800 2002-04-05
37
Sinapis, Ipomoea, Matricaria, Abutilon and Sida from amongst the annuals, and
Convolvulus, Cirsium, Rumex and Artemisia in the case of the perennial weeds.
The active compounds according to the invention also effect outstanding
control of
harmful plants which occur under the specific conditions of rice-growing such
as, for
example, Sagittaria, Alisma, Eleocharis, Scirpus and ~Cyperus.
If the compounds according to the invention are applied to the soil surface
prior to
germination, then the weed seedlings are either prevented completely from
emerging,
or the weeds grow until they have reached the cotyledon stage but then their
growth
stops, and, eventually, after three to four weeks have elapsed, they die
completely.
If the active compounds are applied post-emergence to the green parts of the
plants,
growth also stops drastically a very short time after the treatment and the
weed plants
remain at the developmental stage of the point in time of application, or they
die
completely after a certain time, so that in this manner competition from the
weeds,
which is harmful to the crop plants, is eliminated at a very early point in
time and in a
sustained manner.
Although the compounds according to the invention have an excellent herbicidal
activity against monocotyledonous and dicotyledonous weeds, crop plants of
economically important crops, for example wheat, barley, rye, rice, corn,
sugar beet,
cotton and soya, are not damaged at all, or only to a negligible extent. For
these
reasons, the present compounds are highly suitable for selectively controlling
undesired plant growth in plantings of agriculturally useful plants.
In addition, the substances according to the invention have outstanding growth-
regulating properties in crop plants. They engage in the plant metabolism in a
regulating manner and can thus be employed for the targeted control of plant
constituents and for facilitating harvesting, such as for example by provoking
desiccation and stunted growth. Furthermore, they are also suitable for
generally
regulating and inhibiting undesirable vegetative growth, without destroying
the plants
in the process. Inhibition of vegetative growth plays an important role in
many
monocotyledonous and dicotyledonous crops because lodging can be reduced
hereby,
or prevented completely.
CA 02386800 2002-04-05
38
Owing to their herbicidal and plant-growth-regulatory properties, the active
compounds
can also be employed for controlling harmful plants in crops of known or still
to be
developed genetically engineered plants. The transgenic plants generally have
particularly advantageous properties, for example resistance to certain
pesticides, in
particular certain herbicides, resistance to plant diseases or causative
organisms of
plant diseases, such as certain insects or microorganisms such as fungi,
bacteria or
viruses. Other particular properties relate, for example, to the quantity,
quality, storage
stability, composition and to specific ingredients of the harvested product.
Thus,
transgenic plants having an increased starch content or a modified quality of
the starch
or those having a different fatty acid composition of the harvested product
are known.
The use of the compounds of the formula (I) according to the invention or
their salts in
economically important transgenic crops of useful and ornamental plants, for
example
of cereals, such as wheat, barley, rye, oats, millet, rice, manioc and corn,
or else in
crops of sugar beet, cotton, soya, oilseed rape, potato, tomato, pea and other
vegetable species is preferred.
The compounds of the formula (i) can preferably be used as herbicides in crops
of
useful plants which are resistant or which have been made resistant by genetic
engineering toward the phytotoxic effects of the herbicides.
Conventional ways of preparing novel plants which have modified properties
compared to known plants comprise, for example, traditional breeding methods
and
the generation of mutants. Alternatively, novel plants having modified
properties can
be produced with the aid of genetic engineering methods (see, for example,
EP-A-0221044, EP-A-0131624). For example, there have been described several
cases of
genetically engineered changes in crop plants in order to modify the starch
synthesized in the plants (for example WO 92111376, WO 92114827 and
WO 91/19806),
transgenic crop plants which are resistant to certain herbicides of the
glufosinate-type (cf., for example, EP-A-0242236, EP-A-0242246) or
glyphosate-type (WO 92100377), or of the sulfonylurea-type (EP-A-0257993,
US-A-5013659),
CA 02386800 2002-04-05
39
transgenic crop plants, for example cotton, having the ability to produce
Bacillus
thuringiensis toxins (Bt toxins) which impart resistance to certain pests to
the
plants (EP-A-0142924, EP-A-0193259),
transgenic crop plants having a modified fatty acid composition (WO 91/13972).
Numerous molecular biological techniques which allow the preparation of novel
transgenic plants having modified properties are known in principle; see, for
example,
Sambrook et al., 1989, Molecular Cloning, A Laboratory Manual, 2nd ed. Cold
Spring
Harbor Laboratory Press, Cold Spring Harbor, NY; or Winnacker "Gene and Klone"
[Genes and Clones], VCH Weinheim, 2nd edition 1996, or Christou, "Trends in
Plant
,~.,. Science" 1 (1996) 423-431 ).
In order to carry out such genetic engineering manipulations, it is possible
to introduce
nucleic acid molecules into plasmids which allow a mutagenesis or a change in
the
sequence to occur by recombination of DNA sequences. Using the abovementioned
standard processes it is possible, for example, to exchange bases, to remove
partial
sequences or to add natural or synthetic sequences. To link the DNA fragments
with
each other, it is possible to attach adaptors or linkers to the fragments.
Plant cells having a reduced activity of a gene product can be prepared, for
example,
by expressing at least one appropriate antisense-RNA, a sense-RNA to achieve a
cosuppression effect, or by expressing at least one appropriately constructed
ribozyme
which specifically cleaves transcripts of the abovementioned gene product.
To this end, it is possible to employ both DNA molecules which comprise the
entire
coding sequence of a gene product including any flanking sequences that may be
present, and DNA molecules which comprise only parts of the coding sequence,
it
being necessary for these parts to be long enough to cause an antisense effect
in the
cells. It is also possible to use DNA sequences which have a high degree of
homology
to the coding sequences of a gene product but which are not entirely
identical.
When expressing nucleic acid molecules in plants, the synthesized protein can
be
localized in any desired compartment of the plant cell. However, to achieve
localization
in a certain compartment, it is, for example, possible to link the coding
region with DNA
CA 02386800 2002-04-05
sequences which ensure localization in a certain compartment. Such sequences
are
known to the person skilled in the art (see, for example, Braun et al., EMBO
J. 11
(1992), 3219-3227; Wolter et al., Proc. Natl. Acad. Sci. USA 85 (1988), 846-
850;
Sonnewald et al., Plant J. 1 (1991 ), 95-106).
5
The transgenic plant cells can be regenerated to whole plants using known
techniques. The transgenic plants can in principle be plants of any desired
plant
species, i.e. both monocotyledonous and dicotyledonous plants.
10 In this manner, it is possible to obtain transgenic plants which have
modified properties
,~", by overexpression, suppression or inhibition of homologous (= natural)
genes or gene
sequences or by expression of heterologous (= foreign) genes or gene
sequences.
The compounds (I) according to the invention can preferably be used in
transgenic
15 crops which are resistant to herbicides selected from the group consisting
of the
sulfonylureas, imidazolinones, glufosinate-ammonium or glyphosate-
isopropylammonium and analogous active compounds.
When using the active compounds according to the invention in transgenic
crops, in
20 addition to the effects against harmful plants which can be observed in
other crops,
there are frequently effects which are specific for the application in the
respective
transgenic crop, for example a modified or specifically broadened spectrum of
weeds
which can be controlled, modified application rates which can be used for the
application, preferably good combinability with the herbicides to which the
transgenic
25 crop is resistant, and an effect on the growth and the yield of the
transgenic crop
plants.
The invention therefore also provides for the use of the compounds (1)
according to the
invention as herbicides for controlling harmful plants in transgenic crop
plants.
The compounds according to the invention can be applied in the customary
formulations in the form of wettable powders, emulsifiable concentrates,
sprayable
solutions, dusts or granules. The invention therefore also provides herbicidal
and
plant-growth-regulating compositions comprising compounds of the formula (I).
CA 02386800 2002-04-05
41
The compounds of the formula (I) can be formulated in various ways depending
on the
prevailing biological andlor chemico-physical parameters. Examples of suitable
formulation options are: wettable powders {WP), water-soluble powders (SP),
water-
soluble concentrates, emulsifiable concentrates (EC), emulsions (EW), such as
oil-in-
water and water-in-oil emulsions, sprayable solutions, suspension concentrates
(SC),
oil- or water-based dispersions, oil-miscible solutions, capsule suspensions
(CS),
dusts (DP), seed-dressing compositions, granules for broadcasting and soil
application, granules (GR) in the form of microgranules, spray granules,
coating
granules and adsorption granules, water-dispersible granules (WG), water-
soluble
",~,, granules (SG), ULV formulations, microcapsules and waxes.
These individual formulation types are known in principle and are described,
for
example, in Winnacker-Kuchler, "Chemische Technologic" [Chemical Technology],
Volume 7, C. Hauser Verlag Munich, 4th edition 1986; Wade van Valkenburg,
"Pesticide Formulations", Marcel Dekker, N.Y., 1973; K. Martens, "Spray
Drying"
Handbook, 3rd ed. 1979, G. Goodwin Ltd. London.
The necessary formulation auxiliaries, such as inert materials, surfactants,
solvents
and other additives, are likewise known and are described, for example, in:
Watkins,
"Handbook of Insecticide Dust Diluents and Carriers", 2nd ed., Darland Books,
Caldwell N.J., H.v. Olphen, "Introduction to Clay Colloid Chemistry"; 2nd ed.,
J. Wiiey
& Sons, N.Y.; C. Marsden, "Solvents Guide"; 2nd ed., Interscience, N.Y. 1963;
McCutcheon's "Detergents and Emulsifiers Annual", MC Publ. Corp., Ridgewood
N.J.;
Sisley and Wood, "Encyclopedia of Surface Active Agents", Chem. Publ. Co.
Inc., N.Y.
1964; Schonfeldt, "Grenzflachenaktive Athylenoxidaddukte" [Surface-active
ethylene
oxide adducts], Wiss. Verlagsgesell., Stuttgart 1976; Winnacker-Kiachler,
"Chemische
Technologic" [Chemical Technology], Volume 7, C. Hauser Verlag Munich, 4th
edition
1986.
Based on these formulations it is also possible to produce combinations with
other
pesticidally active substances, for example insecticides, acaricides,
herbicides and
fungicides, and also with safeners, fertilizers andlor growth regulators, for
example in
the form of a ready-mix or tank mix.
CA 02386800 2002-04-05
42
Wettable powders are preparations which are uniformly dispersible in water and
which,
in addition to the active compound and as well as a diluent or inert
substance, also
contain surfactants of ionic and/or nonionic type (wetting agents,
dispersants), for
example polyethoxylated alkyl phenols, polyethoxylated fatty alcohols,
polyethoxylated
fatty amines, fatty alcohol polyglycol ethersulfates, alkanesulfonates,
alkylbenzenesulfonates, sodium ligninsulfonate, sodium 2,2'-dinaphthylmethane-
6,6'-
disulfonate, sodium dibutylnaphthalenesulfonate or else sodium
oleoylmethyltaurinate.
To prepare the wettable powders, the herbicidally active compounds are finely
ground,
for example in customary apparatuses such as hammer mills, fan mills and air-
jet mills,
'""' and are mixed simultaneously or subsequently with the formulation
auxiliaries.
Emulsifiable concentrates are prepared by dissolving the active compound in an
organic solvent, for example butanol, cyclohexanone, dimethylformamide, xylene
or
else relatively high-boiling aromatics or hydrocarbons or mixtures of the
organic
solvents, with the addition of one or more surfactants of ionic andlor
nonionic type
(emulsifiers). Examples of emulsifiers which can be used are calcium
alkylarylsulfonates, such as Ca dodecylbenzenesulfonate, or nonionic
emulsifiers,
such as fatty acid polyglycol esters, alkylaryl polyglycol ethers, fatty
alcohol polyglycol
ethers, propylene oxide-ethylene oxide condensation products, alkyl
polyethers,
sorbitan esters, for example sorbitan fatty acid esters or polyoxyethylene
sorbitan
..~. esters, for example polyoxyethylene sorbitan fatty acid esters.
Dusts are obtained by grinding the active compound with finely divided solid
substances, for example talc, natural clays, such as kaolin, bentonite and
pyrophyllite,
or diatomaceous earth.
Suspension concentrates can be water- or oil-based. They can be prepared, for
example, by wet milling using commercially customary bead mills, with or
without the
addition of surfactants as already mentioned above, for example, in the case
of the
other formulation types.
Emulsions, for example oil-in-water emulsions (EW), can be prepared for
example by
means of stirrers, colloid mills and/or static mixers using aqueous organic
solvents
CA 02386800 2002-04-05
43
and, if desired, surtactants as already mentioned above, for example, in the
case of
the other formulation types.
Granules can be prepared either by spraying the active compound onto
adsorptive,
granulated inert material or by applying active-compound concentrates to the
surface
of carriers such as sand, kaolinites or granulated inert material, by means of
adhesive
binders, for example polyvinyl alcohol, sodium polyacrylate or else mineral
oils.
Suitable active compounds can also be granulated in the manner which is
customary
for the preparation of fertilizer granules, if desired as a mixture with
fertilizers.
f"" Water-dispersible granules are generally prepared by the customary
processes, such
as spray-drying, fluidized-bed granulation, disk granulation, mixing using
high-speed
mixers, and extrusion without solid inert material. For the preparation of
disk, fluidized-
bed, extruder and spray granules, see for example processes in "Spray-Drying
Handbook" 3rd ed. 1979, G. Goodwin Ltd., London; J.E. Browning,
"Agglomeration",
Chemical and Engineering 1967, pages 147 ff; "ferry's Chemical Engineer's Hand-
book", 5th ed., McGraw-Hill, New York 1973, pp. 8-57.
For further details on the formulation of crop protection products, see for
example
G.C. Klingman, "Weed Control as a Science", John Wiley and Sons., Inc., New
York,
1961, pages 81-96 and J.D. Freyer, S.A. Evans, "Weed Control Handbook", 5th
ed.,
,,.., Blackwell Scientific Publications, Oxford, 1968, pages 101-103.
The agrochemical formulations generally contain from 0.1 to 99% by weight, in
particular from 0.1 to 95% by weight, of active compound of the formula (I).
In wettable powders the concentration of active compound is, for example, from
about
10 to 90% by weight, the remainder to 100% by weight consisting of customary
formulation constituents. In emulsifiable concentrates the concentration of
active
compound can be from about 1 to 90%, preferably from 5 to 80%, by weight.
Formulations in the form of dusts contain from 1 to 30% by weight of active
compound,
preferably most commonly from 5 to 20% by weight of active compound, while
sprayable solutions contain from about 0.05 to 80%, preferably from 2 to 50%,
by
weight of active compound. In the case of water-dispersible granules, the
content of
active compound depends partly on whether the active compound is in lipuid or
solid
CA 02386800 2002-04-05
44
form and on the granulation auxiliaries, fillers, etc. that are used. In water-
dispersible
granules the content of active compound, for example, is between 1 and 95% by
weight, preferably between 10 and 80% by weight.
In addition, said formulations of active compound may comprise the tackifiers,
wetting
agents, dispersants, emulsifiers, penetrants, preservatives, antifreeze
agents,
solvents, fillers, carriers, colorants, antifoams, evaporation inhibitors and
pH and
viscosity regulators which are customary in each case.
The compounds of the formula (I) or their salts can be used as such or
combined in
~"'" the form of their preparations (formulations) with other pesticidally
active compounds,
such as, for example, insecticides, acaricides, nematicides, herbicides,
fungicides,
safeners, fertilizers andlor growth regulators, for example as finished
formulations or
tank mixes.
Suitable active compounds which can be combined with the active compounds
according to the invention in mixed formulations or in a tank mix are, for
example,
known active compounds, as described, for example, in Weed Research 26, 441-
445
(1986), or in "The Pesticide Manual", 10th edition, The British Crop
Protection Council
and the Royal Soc. of Chemistry, 1994, and in the literature cited therein.
For example,
the following active compounds may be mentioned as herbicides or plant-growth
,,,~.~" regulators which are known from the literature and which can be
combined with the
compounds of the formula (I) (note: the compounds are either referred to by
the
"common name" in accordance with the International Organization for
Standardization
(ISO) or by the chemical names, if appropriate together with a customary code
number):
acetochlor; acifluorfen(-sodium); aclonifen; AKH 7088, i.e. [[[1-[5-[2-chloro-
4-(trifluoromethyl)phenoxy]-2-nitrophenyl]-2-
methoxyethylidene]amino]oxy]acetic acid
and its methyl ester; alachlor; alloxydim(-sodium); ametryn; amidochlor,
amidosulfuron;
amitrol; AMS, i.e. ammonium sulfamate; anilofos; asulam; atrazine; azafenidin;
azimsulfuron (DPX-A8947); aziprotryn; barban; BAS 516 H, i.e. 5-fluoro-2-
phenyl-4H-
3,1-benzoxazin-4-one; beflubutamid; benazolin(-ethyl); benfluralin;
benfuresate;
bensulfuron(-methyl); bensulide; bentazone; benzobicyclone; benzofenap;
benzofluor;
benzoylprop(-ethyl); benzthiazuron; bialaphos; bifenox; bispyribac(-sodium);
bromacil;
CA 02386800 2002-04-05
bromobutide; bromofenoxim; bromoxynil; bromuron; buminafos; busoxinone;
butachlor; butafenacil; butamifos; butenachlor; buthidazole; butralin;
butroxydim;
butylate; cafenstrole (CH-900); carbetamide; cafentrazone(-ethyl) (ICI-A0051
);
caloxydim, CDAA, i.e. 2-chloro-N,N-di-2-propenylacetamide; CDEC, i.e. 2-
chloroallyl
5 diethyldithiocarbamate; chlomethoxyfen; chloramben; chlorazifop-butyl;
chlormesulon
(ICI-A0051 ); chlorbromuron; chlorbufam; chlorfenac; chlorflurecol-methyl;
chloridazon;
chlorimuron(-ethyl); chlornitrofen; chlorotoluron; chloroxuron; chlorpropham;
chlorsulfuron; chlorthal-dimethyl; chlorthiamid; chlortoluron, cinmethylin;
cinosulfuron;
clethodim; cinidon(-methyl), clefoxydim, clodinafop and its ester derivatives
(for
10 example clodinafop-propargyl); clomazone; clomeprop; cloproxydim;
clopyralid;
clopyrasulfuron(-methyl); cloransulam(-methyl); cumyluron (JC 940); cyanazine;
cycloate; cyclosulfamuron (AC 104); cycloxydim; cycluron; cyhalofop and its
ester
derivatives (for example butyl-ester DEH-112); cyperquat; cyprazine;
cyprazole;
daimuron; 2,4-D; 2,4-DB; dalapon; desmedipham; desmetryn; di-allate; dicamba;
15 dichlobenil; dichlorprop; diclofop and its esters such as diclofop-methyl;
diclosulam,
diethatyl(-ethyl); difenoxuron; difenzoquat; diflufenican; diflufenzopyr;
dimefuron;
dimepiperate; dimethachlor; dimethametryn; dimethenamid (SAN-582H);
dimethazone,
dimexyflam, dimethipin; dimetrasulfuron, dinitramine; dinoseb; dinoterb;
diphenamid;
dipropetryn; diquat; dithiopyr; diuron; DNOC; eglinazine-ethyl; EL 77, i.e. 5-
cyano-
20 1-(1,1-dimethylethyl)-N-methyl-1 H-pyrazole-4-carboxamide; endothal;
epoprodan,
EPTC; esprocarb; ethalfluralin; ethametsulfuron-methyl; ethidimuron; ethiozin;
ethofumesate; ethoxysulfuron, etobenzanid (NW 52); F5231, i.e. N-[2-chloro-4-
fluoro-
5-[4-(3-fluoropropyl)-4,5-dihydro-5-oxo-1 H-tetrazol-1-yl]-
phenyl]ethanesulfonamide;
ethoxyfen and its esters (for example ethyl ester, HN-252); fenoprop; fenoxan,
25 fenoxaprop and fenoxaprop-P and their esters, for example fenoxaprop-P-
ethyl and
fenoxaprop-ethyl; fenoxydim; fentrazamide; fenuron; flamprop(-methyl or -
isopropyl or
-isopropyl-L); flazasulfuron; floazulate, florasulam; fluazifop and fluazifop-
P and their
esters, for example fluazifop-butyl and fluazifop-P-butyl; flucarbazone(-
sodium);
fluchloralin; flumetsulam; flumeturon; flumiclorac(-pentyl); flumioxazin (S-
482);
30 flumipropyn; fluometuron; fluorochloridone, fluorodifen; fluoroglycofen(-
ethyl);
flupoxam (KNW-739); flupropacil CUBIC-4243); flupyrsulfuron(-methyl, or -
sodium);
flurenol(-butyl); fluridone; flurochloridone; fluroxypyr(-meptyl);
flurprimidol, flurtamone;
fluthiacet(-methyl); fluthiamide; fomesafen; fosamine; furyloxyfen;
glufosinate(-
ammonium); glyphosate(-isopropylammonium); halosafen; halosulfuron(-methyl)
and
CA 02386800 2002-04-05
46
its esters (for example the methyl ester, NC-319); haloxyfop and its esters;
haloxyfop-
P (= R-haloxyfop) and its esters; hexazinone; imazamethabenz(-methyl);
imazapyr;
imazaquin and salts such as the ammonium salts; imazamethapyr; imazamox;
imazapic, imazethamethapyr; imazethapyr, imazosulfuron; indanofan; ioxynil;
isocarbamid; isopropalin; isoproturon; isouron; isoxaben; isoxachlortole;
isoxaflutole;
isoxapyrifop; karbutilate; lactofen; lenacil; linuron; MCPA; MCPB; mecoprop;
mefenacet; mefluidid; mesotrione; metamitron; metazachlor; methabenzthiazuron;
metham; methazole; methoxyphenone; methyldymron; metabenzuron,
methobenzuron; metobromuron; (alpha-)metolachlor; metosulam (XRD 511 );
metoxuron; metribuzin; metsulfuron-methyl; MH; molinate; monalide;
monocarbamide
dihydrogensulfate; monolinuron; monuron; MT 128, i.e. 6-chloro-N-(3-chloro-2-
propenyl)-5-methyl-N-phenyl-3-pyridazinamine; MT 5950, i.e. N-[3-chloro-4-(1-
methylethyl)-phenyl]-2-methylpentanamide; naproanilide; napropamide; naptalam;
NC
310, i.e. 4-(2,4-dichlorobenzoyl)-1-methyl-5-benzyloxypyrazole; neburon;
nicosulfuron;
nipyraclophen; nitralin; nitrofen; nitrofluorfen; norflurazon; orbencarb;
oryzalin;
oxadiargyl (RP-020630); oxadiazone; oxasulfuron; oxaciclomefone; oxyfluorfen;
paraquat; pebulate; pelargonic acid; pendimethalin; pentoxazone; perfluidone;
phenisopham; phenmedipham; picloram; picolinafen; piperophos; piributicarb;
pirifenop-butyl; pretilachlor; primisulfuron(-methyl); procarbazone(-sodium);
procyazine; prodiamine; profluralin; proglinazine(-ethyl); prometon;
prometryn;
propachlor; propanil; propaquizafop and its esters; propazine; propham;
propisochlor;
propyzamide; prosulfalin; prosulfocarb; prosulfuron (CGA-152005); prynachlor;
pyroflufen(-ethyl); pyrazolinate; pyrazon; pyrazosulfuron(-ethyl);
pyrazoxyfen;
pyribenzoxim; pyributicarb; pyridafoi; pyridate; pyriminobac(-methyl);
pyrithiobac(-
sodium) (ICIH-2031 ); pyroxofop and its esters (for example propargyl ester);
quinclorac;
quinmerac; quinoclamine, quinofop and its ester derivatives, quizalofop and
quizalofop-P and their ester derivatives, for example quizalofop-ethyl;
quizalofop-P-tefuryl and -ethyl; renriduron; rimsulfuron (DPX-E 9636); S 275,
i.e. 2-[4-
chloro-2-fluoro-5-(2-propynyloxy)phenyl]-4,5,6,7-tetrahydro-2H-indazole;
secbumeton;
sethoxydim; siduron; simazine; simetryn; SN 106279, i.e. 2-[[7-[2-chloro-4-
(trifluoromethyl)phenoxy]-2-naphthalenyl]oxy]propanoic acid and its methyl
ester;
sulcotrione; sulfentrazone (FMC-97285, F-6285); sulfazuron; sulfometuron(-
methyl);
sulfosate (ICI-A0224); sulfosulfuron; TCA; tebutam (GCP-5544); tebuthiuron;
tepraloxydim; terbacil; terbucarb; terbuchlor; terbumeton; terbuthylazine;
terbutryn;
CA 02386800 2002-04-05
47
TFH 450, i.e. N,N-diethyl-3-[(2-ethyl-6-methylphenyl)sulfonyl]-1 H-1,2,4-
triazole-1-carboxamide; thenylchlor (NSK-850); thiafluamide; thiazafluron;
thiazopyr
(Mon-13200); thidiazimin (SN-24085); thifensulfuron(-methyl); thiobencarb;
tiocarbazil;
tralkoxydim; tri-allate; triasulfuron; triaziflam; triazofenamide; tribenuron(-
methyl);
triclopyr; tridiphane; trietazine; trifluralin; triflusulfuron and esters
(e.g. methyl ester,
DPX-66037); trimeturon; tritosulfuron; tsitodef; vernolate; WL 110547, i.e. 5-
phenoxy-
1-[3-(trifluoromethyl)phenyl]-1H-tetrazole; UBH-509; D-489; LS 82-556; KPP-
300;
NC-324; NC-330; KH-218; DPX-N8189; SC-0774; DOWCO-535; DK-8910; V-53482;
PP-600; MBH-001; KIH-9201; ET-751; KIH-6127 and KIH-2023.
,~ Of particular interest is the selective control of harmful plants in crops
of useful and
ornamental plants. Although the compounds (I) according to the invention have
very
good to satisfactory selectivity in a large number of crops, it is possible in
principle that
phytotoxicity in the crop plants can occur in some crops and, in particular,
when the
compounds (I) are mixed with other herbicides which are less selective. In
this respect,
combinations of the compounds (I) according to the invention which contain the
compounds (I), or their combinations with other herbicides or pesticides, and
safeners
are of particular interest. The safeners, which are employed in such amounts
that they
act as antidotes, reduce the phytotoxic side effects of the
herbicides/pesticides used,
for example in economically important crops such as cereals (wheat, barley,
rye, corn,
rice, millet), sugar beet, sugar cane, oilseed rape, cotton and soya,
preferably cereal.
,""" Suitable safeners for the compounds (I) and their combinations with other
pesticides
are, for example, the following groups of compounds:
a) Compounds of the type of dichlorophenylpyrazoline-3-carboxylic acid,
preferably compounds such as ethyl 1-(2,4-dichlorophenyl)-
5-(ethoxycarbonyl)-5-methyl-2-pyrazoline-3-carboxylate (S1-1 ) ("mefenpyr-
diethyl", PM, pp. 781-782), and related compounds, as described in
W O 91 /07874,
b) Derivatives of dichlorophenylpyrazole carboxylic acid, preferably compounds
such as ethyl 1-(2,4-dichlorophenyl)-5-methylpyrazole-3-carboxylate (S1-2),
ethyl 1-(2,4-dichlorophenyl)-5-isopropylpyrazole-3-carboxylate (S1-3), ethyl
1-(2,4-dichlorophenyl)-5-( 1,1-dimethylethyl)pyrazole-3-carboxylate (S 1-4),
ethyl
1-(2,4-dichlorophenyl)-5-phenylpyrazole-3-carboxylate (S1-5) and related
CA 02386800 2002-04-05
48
compounds as described in EP-A-333 131 and EP-A-269 806.
c) Compounds of the type of the triazolecarboxylic acids, preferably compounds
such as fenchlorazole(ethyl ester), i.e. ethyl 1-(2,4-dichlorophenyl)-
5-trichloromethyl-(1H)-1,2,4-triazole-3-carboxylate (S1-6) and related
compounds as described in EP-A-174 562 and EP-A-346 620.
d) Compounds of the type of the 5-benzyl- or 5-phenyl-2-isoxazoline-3-
carboxylic
acid, or the 5,5-Biphenyl-2-isoxazoline-3-carboxylic acid, preferably
compounds
such as ethyl 5-(2,4-dichlorobenzyl)-2-isoxazoline-3-carboxylate {S1-7) or
ethyl
5-phenyl-2-isoxazoline-3-carboxylate (S1-8) and related compounds, as
described in WO 91108202, or ethyl 5,5-Biphenyl-2-isoxazolinecarboxylate (S1-
°~' 9) ("isoxadifen-ethyl") or its n-propyl ester (S1-10) or ethyl 5-(4-
fluorophenyl)-5-
phenyl-2-isoxazoline-3-carboxylate (S1-11), as described in the German patent
application (V110-A-95/07897).
e) Compounds of the type of the 8-quinolineoxyacetic acid (S2), preferably
1-methylhex-1-yl (5-chloro-8-quinolineoxy) acetate (common name
"cloquintocet-mexyl" (S2-1 ) (see PM, pp. 263-264)
1,3-dimethylbut-1-yl (5-chloro-8-quinolineoxy)acetate (S2-2),
4-allyloxybutyl (5-chloro-8-quinolineoxy)acetate (S2-3),
1-allyloxyprop-2-yl (5-chloro-8-quinolineoxy)acetate (S2-4),
ethyl (5-chloro-8-quinolineoxy)acetate (S2-5),
methyl (5-chloro-8-quinolineoxy)acetate (S2-6),
,,~., allyl (5-chloro-8-quinolineoxy)acetate (S2-7),
2-(2-propylideneiminoxy)-1-ethyl (5-chloro-8-quinolineoxy)acetate (S2-8),
2-oxoprop-1-yl (5-chloro-8-quinolineoxy)acetate (S2-9)
and related compounds, as described in EP-A-86 750, EP-A-94 349 and
EP-A-191 736 or EP-A-0 492 366.
f) Compounds of the type of the (5-chloro-8-quinolineoxy)malonic acid,
preferably
compounds such as diethyl (5-chloro-8-quinolineoxy)malonate, diallyl
(5-chloro-8-quinolineoxy)malonate, methyl ethyl
(5-chloro-8-quinolineoxy)malonate and related compounds, as described in
EP-A-0 582 198.
g) Active compounds of the type of the phenoxyacetic or -propionic acid
derivatives or the aromatic carboxylic acids, such as, for example,
2,4-dichlorophenoxyacetic acid (esters) (2,4-D),
CA 02386800 2002-04-05
49
4-chloro-2-methylphenoxypropionic esters (mecoprop), MCPA or 3,6-dichloro-
2-methoxybenzoic acid (esters) (dicamba).
h) Active compounds of the type of the pyrimidines, which are used as soil-
acting
safeners in rice, such as, for example,
"fenclorim" (PM, pp. 512-511 ) (= 4,6-dichloro-2-phenylpyrimidine), which is
known as safener for pretilachlor in sown rice,
i) Active compounds of the type of the dichloroacetamides, which are
frequently
used as pre-emergent safeners (soil-acting safeners), such as, for example,
"dichlormid" (PM, pp. 363-364) (= N,N-diallyl-2,2-dichloroacetamide),
"R-29148" (= 3-dichloroacetyl-2,2,5-trimethyl-1,3-oxazolidine from Stauffer),
"benoxacor" (PM, pp. 102-103) (= 4-dichloroacetyl-3,4-dihydro-3-methyl-2H-1,4-
benzoxazine),
"PPG-1292" (= N-allyl-N-[(1,3-dioxolan-2-yl)methyl]dichloroacetamide from PPG
Industries),
"DK-24" (= N-allyl-N-[(allylaminocarbonyl)methyl]dichloroacetamide from Sagro-
Chem),
"AD-67" or "MON 4660" (= 3-dichloroacetyl-1-oxa-3-aza-spiro[4,5]decane from
Nitrokemia or Monsanto),
"diclonon" or "BAS145138" or "l.AB145138" (= 3-dichloroacetyl-2,5,5-trimethyl-
1,3-diazabicyclo[4.3.0]nonane from BASF' and
"furilazol" or "MON 13900" (see PM, 637-638) (_ (RS)-3-dichloroacetyl-5-(2-
",.., furyl)-2,2-dimethyloxazolidine)
j) Active compounds of the type of the dichloroacetone derivatives, such as,
for
example,
"MG 191" (CAS-Reg. No. 96420-72-3) (= 2-dichloromethyl-2-methyl-1,3-
dioxolane from Nitrokemia), which is known as safener for corn,
k) Active compounds of the type of the oxyimino compounds, which are known as
seed dressings, such as, for example,
"oxabetrinil" (PM, pp. 902-903) (_ (Z)-1,3-dioxolan-2-ylmethoxy-
imino(phenyl)acetonitrile), which is known as seed dressing safener for millet
against metolachlor damage,
"fluxofenim" (PM, pp. 613-614) (= 1-(4-chlorophenyl)-2,2,2-trifluoro-l-
ethanone
O-(1,3-dioxolan-2-ylmethyl) oxime), which is known as seed dressing safener
for millet against metolachlor damage,
CA 02386800 2002-04-05
"cyometrinil" or "-CGA-43089" (PM, p. 1304) (_ (Z)-
cyanomethoxyimino(phenyl)acetonitrile), which is known as seed dressing
safener for millet against metolachlor damage,
I) Active compounds of the type of the thiazolecarboxylic esters, which are
known
5 as seed dressings, such as, for example,
"flurazol" (PM, pp. 590-591 ) (= benzyl 2-chloro-4-trifluoromethyl-1,3-
thiazole-5-
carboxylate), which is known as seed dressing safener for millet against
alachlor and metolachlor damage,
m) Active compounds of the type of the naphthalenedicarboxylic acid
derivatives,
10 which are known as seed dressings, such as, for example,
"naphthalic anhydride" (PM, p. 1342) (= 1,8-naphthalenedicarboxylic
anhydride), which is known as seed dressing safener for corn against
thiocarbamate herbicide damage,
n) Active compounds of the type of the chromanacetic acid derivatives, such
as,
15 for example,
"CL 304415" (CAS-Reg. No. 31541-57-8) (= 2-(4-carboxychroman-4-yl)acetic
acid from American Cyanamid), which is known as safener for com against
imidazolinone damage,
o) Active compounds which, in addition to a herbidical action against harmful
20 plants, also have safener action in crop plants such as rice, such as, for
example,
,,~.. "dimepiperate" or "MY-93" (PM, pp. 404-405) (= S-1-methyl-1-phenylethyl
piperidine-1-thiocarboxylate), which is known as safener for rice against the
herbicide molinate,
25 "daimuron" or "SK 23" (PM, p. 330) (= 1-(1-methyl-1-phenylethyl)-3-p-
tolylurea),
which is known as safener for rice against the herbicide imazosulfuron,
"cumyluron" _ "JC-940" (= 3-(2-chlorophenylmethyl)-1-(1-methyl-
1-phenylethyl)urea, see JP-A-60087254), which is known as safener for rice
against damage by some herbicides,
30 "methoxyphenon" or "NK 049" (= 3,3'-dimethyl-4-methoxybenzophenone),
which is known as safener for rice against damage by some herbicides,
"CSB" (= 1-bromo-4-(chloromethylsulfonyl)benzene) (CAS-Reg. No. 54091-06-4
from Kumiai), which is known as safener against damage ~y some herbicides in
rice
CA 02386800 2002-04-05
51
p) N-Acylsulfonamides of the formula (S3) and salts thereof,
R2 Ra
R I O ~ / (R5)m
' -N
~ N \ / o (~)
0
(R3)n
as described in WO-A-97145016,
., q) Acylsulfamoylbenzoamides of the formula (S4), if appropriate also in
salt form,
O
_ O O
II \
\ ~ S N , (RS)m
R2 I X
O
(R3)n Ra
as described in the International Application No. PCT/EP98106097, and
r) Compounds of the formula (S5),
R'
W
RZ ~ ~E)m
Q2 /G (S5)
R3
as described in WO-A 98/13 361,
including the stereoisomers and the salts used in agriculture.
Among the safeners mentioned, (S1-1) and (S1-9) and (S2-1), in particular (S1-
1) and
(S1-9), are of particular interest.
Some of the safeners are already known as herbicides and consequently show, in
addition to the herbicidal action against harmful plants, also protective
action in
connection with crop plants.
The ratios by weight of herbicide (mixture) to safener generally depend on the
CA 02386800 2002-04-05
52
application rate of the herbicide and the efficacy of the safener in question
and can
vary within wide limits, for example in the range from 200:1 to 1:200,
preferably 100:1
to 1:100, in particular 20:1 to 1:20. Analogously to the compounds (I) or
their mixtures,
the safeners can be formulated with other herbicides/pesticides and be
provided and
used as ready-mix or tank mix with the herbicides.
For use, the herbicide or herbicide safener formulations which are present in
commercially available form are, if appropriate, diluted in the customary
manner, for
example using water in the case of wettable powders, emulsifiable
concentrates,
dispersions and water-dispersible granules. Preparations in the form of dusts,
granules
,.- for soil application or broadcasting and sprayable solutions are usually
not further
diluted with other inert substances prior to use.
The application rate of the compounds of the formula (I) required varies with
the
external conditions, such as temperature, humidity, the nature of the
herbicide used
and the like. It can vary within wide limits, for example between 0.001 and
10.0 kg/ha
or more of active substance, but it is preferably between 0.005 and 5 kg/ha,
in
particular between 0.01 and 1 kg/ha of active substance.
In the examples below, the amounts (including percentages) are based on
weight,
unless specifically defined otherwise.
A. Chemical Examples
(A1) 2-Amino-4-[1-(4-fluoro-3-methoxyphenyl)ethyl]amino-6-isopropyl-1,3,5-
triazine
0.35 g (2.1 mmol) of 1-(4-fluoro-3-methoxyphenyl)ethylamine, 0.34 g (2.0 mmol)
of
2-amino-4-chloro-6-isopropyl-1,3,5-triazine and 0.29 g (2.1 mmol) of potassium
carbonate were initially charged in 20 ml of acetonitrile, and the mixture was
heated at
79°C for 8 h. Using a rotary evaporator, the solvent was removed from
the reaction
mixture, and the residue was taken up in water and extracted with ethyl
acetate. The
combined organic phases were dried and filtered, and the solvent was distilled
off
using a rotary evaporator. The residue was purified chromatographically,
giving 0.45 g
(1.47 mmol, 73.7% yield) of the desired product as a solid of melting point
110-113°C.
CA 02386800 2002-04-05
53
(A2) 2-[1-(4-Chloro-3-methylphenyl)ethyl]amino-4-methyl-6-trichloromethyl-
1,3,5-
triazine
0.45 g (2.7 mmol) of 1-(4-chloro-3-methylphenyl)ethylamine and 0.87 g (2.7
mmol) of
2-methyl-4,6-bis(trichloromethyl)-1,3,5-triazine were initially charged in 20
ml of
acetonitrile, and the mixture was heated at 70-75°C for 5 h. Using a
rotary evaporator,
the solvent was removed from the reaction mixture, the residue was taken up in
ethyl
acetate and water and the aqueous phase was then extracted twice with ethyl
acetate.
The combined organic phases were dried and filtered, and the solvent was
distilled off
-. using a rotary evaporator. The residue was purified chromatographically,
giving 0.62 g
(1.63 mmol, 60.4% yield) of the desired produced as an oil.
(A3) Synthesis of 1-(3-bromo-4-fluorophenyl)ethylamine
9.5 g (43.8 mmol) of 3-bromo-4-fluoroacetophenone, 14.35 g (0.23 mol) of
ammonium
formate and 2.3 g (43.0 mmol) of 86% strength formic acid were heated at
160°C, with
removal of water, for 5 h, and 0.75 g (14.0 mmol) of 86% strength formic acid
were
added after 3 h. The reaction mixture was taken up in water and diethyl ether,
the
aqueous phase was extracted twice with diethyl ether and the solvent was
removed
from the combined organic phases using a rotary evaporator. The residue was
mixed
with 10 ml of concentrated hydrochloric acid and heated under reflux for 2 h.
The
content was taken up in water and the aqueous phase was extracted twice with
ethyl
acetate. With ice-cooling, the aqueous phase was made alkaline using 5 M
aqueous
potassium hydroxide solution and again extracted twice with ethyl acetate. The
two
organic phases which were separated off last were combined and dried over
magnesium sulfate, and the solvent was removed from the filtrate using a
rotary
evaporator. This gave 7.25 g (76% yield) of the desired product as an oil.
(A4) Synthesis of 2-amino-4-cyclobutyl-6-trichloromethyl-1,3,5-triazine
At 0°C, a solution of 7.90 g (67 mmol) of cyclobutane carbonyl chloride
in 25 ml of
diethyl ether was added dropwise to a solution of 11.3 g (56 mmol) of
trichloromethylimidoylguanide in 25 ml of diethyl ether. After 30 minutes at
0°C, 8.28 g
CA 02386800 2002-04-05
54
(78 mmol) of triethylamine were added dropwise. The reaction mixture was then
heated under reflux for 10 minutes. For work-up, the content was taken up in
water,
the aqueous phase was extracted with ethyl acetate, the combined organic
phases
were dried and the solvent was removed from the filtrate using a rotary
evaporator.
Recrystallization gave 6 g (38.4% yield) of the desired product.
(A5) Synthesis of 2-amino-4-cyclobutyl-6-(3,5-dichlorobenzyl)amino-1,3,5-
triazine
2.6 g (10 mmol) of 2-amino-4-cyclobutyl-6-trichloromethyl-1,3,5-triazine and
1.71 g
(10 mmol) of 3,5-dichlorobenzylamine in 5 ml of N,N-dimethylformamide were
heated
"~ at 130°C for 2 h. The reaction mixture was fractionated
chromatographically, giving
3.1 g (88.6% yield) of the desired product.
The compounds described in Tables 1 to 10 below are obtained according to or
analogously to Examples A1 to A5 above or the methods described further above
in a
general manner. The abbreviations used in the tables are:
Me - CH3 - methyl
(also in composed radicals, such as methylthio (SMe or -SMe or MeS-),
methylsulfonyl
(S02Me), dimethylamino (NMe2) etc.)
,,.... Ac - COCH3 - acetyl
Bzl - CH2CgH5 - benzyl
(n-)Bu - (n-)C4H9 - n-butyl
t-Bu - tertiary butyl
Et - C2H5 - ethyl
(n-)Pr, i-Pr, c-Pr = (n-), i-, c-CgH~ = n-propyl, isopropyl and cyclopropyl,
respectively
(n-)Pen = n-pentyl
Ph - phenyl
Phys. data - Physical data; if a number is given, this number means the
melting point in °C; "resin" or "oil" refers to the consistency of the
CA 02386800 2002-04-05
non-crystalline compound obtained.
Table 1: Compounds of the formula (1 )
CH3 R4 R5
3
N N R
R6 (1)
H2N N N
H
No. R3 R4 RS R6 R' R8 Phys.
data
1 CH3 CH3 H F H H
2 CH3 CF3 H F H H
3 CH3 OH H F H H
4 CH3 OCH3 H F H H 48
5 CH3 i-Pr H Bzl H H
6 CH3 F H F H H Oil
7 CH3 CI H F H H
"" 8 CH3 Br H F H H
9 CH3 I H t-Bu H H
10 CH3 CH3 H OBzI H H
11 CH3 CF3 H OPh H H
12 CH3 OH H N02 H H Resin
13 CH3 OCH3 H NH2 H H Resin
14 CH3 CH20Me H C6H5 H H
15 CH3 F ~ H NHCOMe H H Resin
16 CH3 CI ', NHCHO H H Resin
H
17 CH3 Br H N(S02Me)2H H Resin
18 CH3 I H NHSOZMe H H Resin
CA 02386800 2002-04-05
ss
No. R3 R4 R5 Rs R' Re Phys.
data
19 CH3 CH3 H SCH3 H H
2D CH3 CF3 H SOCH3 H H
21 CH3 OH H S02NH2 H H
22 CH3 OCH3 H S02NHMe H H
23 CH3 CH20CH3 H F H H
24 CH3 F H S02CH3 H H
25 CH3 CI H CH20CH3 H H
26 CH3 Br H CH2NMe2 H H
27 CH3 I H CH2SCH3 H H
2B CH3 CH3 H F H H
29 CH3 CF3 H CI H H
30 CH3 CH2NMe2 H F H H
31 CH3 CH2S-Me H F H H
32 CH3 CH3 F H H H
33 CH3 CF3 F H H H
34 CH3 F CF3 H H H
36 CH3 CH3 H H CH3 H
36 CH3 CF3 H H CH20CH3 H
37 CH3 OH H H CF3 H
3B CH3 OCH3 H H OCH3 H
39 CH3 CH20CH3 H H N(CH3)2 H
40 CH3 F H H F H
41 CH3 CI H H CI H
42 CH3 Br H H S02CH3 H
43 CH3 I H H S02CH3 H
44 CH3 CH3 H H H F
45 CH3 CF3 H H H F
46 CH3 H CH3 CI H H ~5
CA 02386800 2002-04-05
57
No. R3 R4 RS R6 R' Re Phys.
data
47 CH3 H CF3 F H H
48 CH3 H CH3 F H H Oil
49 CH3 H OCH3 F H H Oil
50 CH3 H N02 F H H
51 CH3 H NH2 F H H Oil
52 CH3 H N(CH3)2 F H H
53 CH3 H NHCOCH3 F H H
54 CH3 H NHCHO F H H
56 CH3 H N(S02Me)2F H H
56 CH3 H NHS02Me F H H
57 CH3 H SMe F H H
58 CH3 H SOMe F H H
99 CH3 H S02NH2 F H H
6o CH3 H S02NHMe F H H
61 CH3 H S02NMez F H H
62 CH3 H S02CH3 F H H
63 CH3 H NHCOMe SOZNH2 H H
,"", 64 CH3 H CH20CH3 F H H
66 CH3 H CH2NMe2 F H H
66 CH3 H CH2SCH3 F H H
67 CH3 H F F H H Oil
68 CH3 H CI F H H Oil
CH3 H Br F H H Resin
7D CH3 H I F H H
71 CH3 H F c-Pr H H Resin
?2 CH3 H F Bzl H H fiesin
73 CH3 H F CH=CH2 H H Resin
74 CH3 H F C---CH H H flesin
CA 02386800 2002-04-05
58
No. R3 R4 RS Rs R' R8 Phys.
data
75 CH3 H F H F H Oil
76 CH3 F H CI F H Oil
77 CHFMe H OMe Br H H Resin
78 CHFMe H Me Br H H Resin
79 CHFMe H N02 Br H H Resin
8o CHFMe H NHZ Br H H Resin
81 CHFMe H N02 CI H H Resin
r-
82 CHFMe H NH2 CI H H Resin
83 CHFMe H OMe F H H Resin
84 CHFMe H N02 F H H Resin
86 CHFMe H NH2 F H H Resin
86 CHFMe OMe H F H H Resin
87 CHFMe F H F H H Resin
8B CHFMe F H H H F Resin
8A CHFMe H F H F H Resin
90 CHFMe H F F H H Resin
91 CHFMe H Me F H H Resin
,,.,..
92 CH3 H F CI H H Resin
93 CH3 H CH3 H N02 H Resin
94 CH3 H CF3 H NH2 H Resin
CH3 H OH H N(CH3)2 H Resin
96 CH3 H OCH3 H NHCOCH3 H Resin
97 CH3 H CH3 H N02 H Resin
98 CH3 H CF3 H NH2 H Resin
99 CH3 H OH H N(CH3)z H Resin
100 CH3 H OCH3 H NHCOCH3 H Resin
101 CH3 H N02 H NHCHO H Resin
102 CH3 H NHZ H N(S02Me)2 H Resin
CA 02386800 2002-04-05
59
No. R3 R4 _ Rs R6 R, RB Phys.
data
103 CH3 H N(CH3)2 H NHSOZMe H Resin
104 CH3 H NHCOCH3 H F H
105 CH3 H NHCHO H CI H
106 CH3 H N(SOZMe)2H Br H
107 CH3 H NHS02Me H I H
108 CH3 H SMe H CH3 H
109 CH3 H SOMe H CF3 H
,,..,. 110 CH3 H S02NH2 H OH H
111 CH3 H S02NHMe H OCH3 H
112 CH3 H S02NMe2 H SCH3 H
113 CH3 H S02CH3 H SOCH3 H
114 CH3 H CH20CH3 H SOZNH2 H
115 CH3 H F H S02NHMe H
116 CH3 H CI H S02NMe2 H
117 CH3 H Br H S02CH3 H
118 CH3 H I H C2H5 H
119 CH3 CH3 CH3 CI H H
,"~",e 12D CH3 CH3 F H CI H
121 CH3 OCH3 CI H F H
122 CH3 OCH3 CH3 H H F
123 CH3 CI H F H CI
124 CH3 H F F F H 53
125 CH3 CI H F OCH3 H
126 CH3 F H CI OCH3 H
127 CH3 F H F F H Oil
128 CH3 F CH3 H CH3 F
129 CH3 F F CI CH3 H
130 CH3 CH3 F CI H F
CA 02386800 2002-04-05
6~
No. R3 R' RS Rs R' Rs Phys.
data
131 CH3 CH3 F F F CH3 Resin
132 CH3 CH3 H CH3 H H
133 CH3 H F CH3 H H
134 CH3 CH3 H CI H H
135 CH3 H -CMe2-(CH2)2-CMe2- H H 64
136 CH3 H -(CH2)4- H H Resin
137 CH3 H -(CHZ)3- H H Resin
13B H H C! CI H H 186
13A CH3 H OCH3 OCH3 H H Resin
140 CH3 H CI H CH=CHEt H
141 CH3 H CI H C =CEt H
142 CH3 H CI H Ph H
143 CH3 H CI H CN H
144 CH3 H CI -(CH2)4- H
145 CH3 H CI -O(CH2)20- H Resin
146 CH3 H CI -OCH20- H Resin
147 CzH5 CH3 H CH3 H H
148 C2H5 F H CH3 H H
149 C2H5 CH3 H CI H H
150 C2H5 H NMe2 CI H H
151 C2H5 H SOzCH3 CH3 H H
152 CH3 H CH3 Br H H
153 CH3 H CH3 I H H
154 C~!-15 H CH3 F H H Resin
156 C~I-15 H CH3 CI H H
156 C~I-15 H CH3 Br H H
~5'l C~I-15 H CH3 I H H
158 C~hi5 H F F H H Resin
CA 02386800 2002-04-05
61
No. R3 R4 RS Rs R' R8 Phys.
data
9 C~iS H F H F H Resin
180 c-Pr H OMe Br H H Resin
161 c-Pr H Me Br H H Resin
162 c-Pr H N02 Br H H Resin
163 c-Pr H NH2 Br H H Resin
164 c-Pr H N02 CI H H Resin
166 c-Pr H NH2 CI H H Resin
6 c-Pr H OMe F H H Resin
167 c-Pr H N02 F H H Resin
168 c-Pr H NH2 F H H Resin
169 c-Pr OMe H F H H Resin
170 c-Pr F H F H H Resin
171 c-Pr F H H H F Resin
172 c-Pr H Me F H H Resin
173 c-Pr H F F H H Resin
174 c-Pr H F H F H Resin
175 Me H CH3 CH20CH3 H H
176 Me H F CH20CH3 H H
177 Me H CI CH20CH3 H H
178 Me H Br CH20CH3 H H
9 Me H CH3 CHzSCH3 H H
180 Me H F CH2SCH3 H H
181 Me H CI CH2SCH3 H H
182 Me H Br CH2SCH3 H H
183 Me H CH3 CH2NMe2 H H
184 Me H F CH2NMe2 H H
X85 Me H CI CH2NMe2 H H
186 Me H Br CH2NMe2 H H
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data
187 Me H CI CH3 H H
188 Me H Br CH3 H H
189 C2H5 H CH3 CH20CH3 H H
190 C2H5 H F CH20CH3 H H
191 C2H5 H CI CH20CH3 H H
192 C2H5 H Br CH20CH3 H H
193 C2H5 H CH3 CH2SCH3 H H
,~ 194 CZHS H F CH2SCH3 H H
195 C2H5 H CI CH2SCH3 H H
196 C2H5 H Br CH2SCH3 H H
197 C2H5 H CH3 CH2NMe2 H H
198 CZHS H F CH2NMe2 H H
199 C2H5 H CI CH2NMe2 H H
200 C2H5 H Br CH2NMe2 H H
201 C2H5 H CI CH3 H H
202 C2H5 H Br CH3 H H
200 C2H5 H F CH3 H H
CA 02386800 2002-04-05
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Table 2: Compounds of the formula (2)
C2Hs R4 R5
3
N N R
H N" ~ R6
N N
R g R7
No. R3 R4 R5 Rs R' R8 Phys.
data
204 CH3 CH3 H F H H
205 CH3 CF3 H F H H
206 CH3 OH H F H H
207 CH3 OCH3 H F H H
208 CH3 i-Pr H CH2C6H5 H H
209 CH3 F H F H H Oil
210 CH3 CI H F H H
211 CH3 Br H F H H
212 CH3 1 H C(CH3)3 H H
213 CH3 CH3 H OCH2CsH5 H H
214 CH3 CF3 H OCsHS H H
215 CH3 OH H N02 H H Resin
216 CH3 OCH3 H NH2 H H Resin
217 CH3 CHZOCH3 H C6H5 H H
218 CH3 F H NHCOCH3 H H Resin
219 CH3 CI H NHCHO H H Resin
220 CH3 Br H N(S02CH3}2H H Resin
221 CH3 I H NHS02CH3 H H Resin
222 CH3 CH3 H SCH3 H H
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No. R3 R4 RS R6 R' Rs Phys.
data
223 CH3 CF3 H SOCH3 H H
224 CH3 OH H S02NH2 H H
225 CH3 OCH3 H S02NHCH3 H H
226 CH3 CH20Me H F H H
227 CH3 F H SOZCH3 H H
22B CH3 CI H CH20CH3 H H
229 CH3 Br H CH2N(CH3)2H H
230 CH3 I H CH2SCH3 H H
231 CH3 CH3 H F H H
232 CH3 CF3 H CI H H
233 CH3 CH2NMe2 H F H H
234 CH3 CH2SMe H F H H
235 CH3 CH3 F H H H
236 CH3 CF3 F H H H
231 CH3 F CF3 H H H
23B CH3 CH3 H H CH3 H
""'~"' 239 CH3 CF3 H H CH20CH3 H
240 CH3 OH H H CF3 H
241 CH3 OCH3 H H OCH3 H
242 CH3 CH20Me H H N(CH3)2 H Resin
243 CH3 F H H F H
244 CH3 CI H H CI H
245 CH3 Br H H S02CH3 H
246 CH3 I H H S02CH3 H
247 CH3 CH3 H H H F
248 CH3 CF3 H H H F
CA 02386800 2002-04-05
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data
249 CH3 H CH3 CI H H 50
250 CH3 H CF3 F H H
251 CH3 H CH3 F H H Oil
252 CH3 H OCH3 F H H 45
253 CH3 H N02 F H H
254 CH3 H NH2 F H H Oil
256 CH3 H N(CH3)2 F H H
256 CH3 H NHCOCH3 F H H
25-!CH3 H NHCHO F H H
258 CH3 H N(S02Me)2F H H
2a~ CH3 H NHSOZMe F H H
260 CH3 H SMe F H H
261 CH3 H SOMe F H H
262 CH3 H S02NH2 F H H
263 CH3 H SOZNHMe F H H
a64 CH3 H S02NMe2 F H H
'"~' 266 CH3 H S02CH3 F H H
266 CH3 H NHCOCH3 SOZNH2 H H
267 CH3 H CH20CH3 F H H
268 CH3 H CH2NMe2 F H H
2B9 CH3 H CH2SCH3 F H H
27n CH3 H F F H H Oil
271 CH3 H CI F H H
272 CH3 H Br F H H 47
273 CH3 H I F H H
274 CH3 H F c-Pr H H Resin
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No. R3 R4 RS Rs R' Re Phys.
data
CH3 H F Bzl H H Resin
276 CH3 H F CH=CH2 H H Resin
2T7 CH3 H F C---CH H H Resin
278 CH3 H F H F H Oil
z7g CH3 F H CI F H 85
2gp CHFMe H OMe Br H H Resin
281 CHFMe H Me Br H H Resin
CHFMe H N02 Br H H Resin
CHFMe H NH2 Br H H Resin
284 CHFMe H NOZ CI H H Resin
2g5 CHFMe H NH2 CI H H Resin
286 CHFMe H OMe F H H Resin
287 CHFMe H NOZ F H H Resin
CHFMe H NHZ F H H Resin
2gg CHFMe OMe H F H H Resin
2gp CHFMe F H F H H Resin
291 CHFMe F H H H F Resin
292 CHFMe H F H F H Resin
293 CHFMe H F F H H Resin
294 CHFMe H Me F H H Resin
295 CH3 H F CI H H Resin
296 CH3 H CH3 H N02 H Resin
297 CH3 H CF3 H NH2 H Resin
298 CH3 H OH H N(CH3)2 H Resin
299 CH3 H OCH3 H NHCOCH3 H Resin
300 CH3 H N02 H NHCHO H Resin
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No. R3 R4 R5 R6 R' R8 Phys.
data
301 CH3 H NH2 H N(S02Me)2H Resin
302 CH3 H N(CH3)2 H NHS02CH3 H Resin
303 CH3 H NHCOCH3 H F H
304 CH3 H NHCHO H CI H
306 CH3 H N(S02Me)zH Br H
306 CH3 H NHS02Me H I H
307 CH3 H SMe H CH3 H
308 CH3 H SOMe H CF3 H
309 CH3 H SOZNH2 H OH H
310 CH3 H SOZNHMe H OCH3 H
311 CH3 H SOZNMe2 H SCH3 H
312 CH3 H S02CH3 H SOCH3 H
313 CH3 H CH20CH3 H S02NH2 H
314 CH3 H F H S02NHCH3 H
315 CH3 H CI H S02NMe2 H
316 CH3 H Br H S02CH3 H
317 CH3 H I H C2H5 H
318 CH3 CH3 CH3 CI H H
319 CH3 CH3 F H CI H
320 CH3 OCH3 CI H F H
32'1 CH3 OCH3 CH3 H H F
322 CH3 CI H F H CI
32;i CH3 H F F F H
324 CH3 CI H F OCH3 H
325 CH3 F H CI OCH3 H
326 CH3 F H F F H
CA 02386800 2002-04-05
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No. R3 R4 RS R6 R' Re Phys.
data
327 CH3 F CH3 H CH3 F
328 CH3 F F CI CH3 H
329 CH3 CH3 F CI H F
330 CH3 CH3 F F F CH3
331 CH3 CH3 H CH3 H H
332 CH3 H F CH3 H H
333 CH3 CH3 H CI H H
334 CH3 CH3
-(CH2)3- CH3 H Resin
336 CH3 H -C(CH3)2-(CH2)2-C(CH3)2- H H 64
336 CH3 H -(CH2)a- H H 60
337 CH3 H OCH3 OCH3 H H 129
338 CH3 H CI H CH=CHEt H
339 CH3 H CI H C ~CEt H
340 CH3 H CI H Ph H
341 CH3 H CI H CN H
342 CH3 H CI -(CH2)a- H
343 CH3 H CI -O(CH2)20- H
344 CH3 H CI -OCH20- H Resin
345 C2H5 CH3 H CH3 H H
346 C2H5 F H CH3 H H
347 C2H5 CH3 H CI H H
348 C2H5 H N(CH3)2 CI H H
349 C2H5 H S02CH3 CH3 H H
360 Me H Me Br H H
351 Me H Me I H H
352 Et H Me F H H Resin
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No. R3 R4 Rs Rs R~ H8 Phys.
data
363 Et H Me CI H H
~4 Et H Me Br H H
356 Et H Me I H H
C~I-IS H F F H H Resin
367 C~I-15 H F H F H Resin
c-Pr H OMe Br H H Resin
3gg c-Pr H Me Br H H Resin
c-Pr H N02 Br H H Resin
361 c-Pr H NH2 Br H H Resin
362 c-Pr H N02 CI H H Resin
c-Pr H NH2 CI H H Resin
364 c-Pr H OMe F H H Resin
~,5 c-Pr H N02 F H H Resin
c-Pr H NH2 F H H Resin
c-Pr OMe H F H H Resin
~g c-Pr F H F H H Resin
'"~'' 369 c-Pr F H H H F Resin
37ipc-Pr H Me F H H Resin
371 c-Pr H F F H H Resin
372 c-Pr H F H F H Resin
373 Me H Me CH20Me H H
374 Me H F CH20Me H H
375 Me H CI CH20Me H H
3716Me H Br CH20Me H H
377 Me H CH3 CH2SMe H H
378 Me H F CH2SMe H H
CA 02386800 2002-04-05
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data
379 Me H CI CH2SMe H H
380 Me H Br CH2SMe H H
381 Me H CH3 CH2NMe2 H H
382 Me H F CH2NMe2 H H
383 Me H CI CHzNMe2 H H
384 Me H Br CH2NMe2 H H
386 Me H CI CH3 H H
",a
386 Me H Br CH3 H H
3l37C2H5 H CH3 CHZOCH3 H H
388 C2H5 H F CH20CH3 H H
38A C2H5 H CI CH20CH3 H H
3B0 C2H5 H Br CH20CH3 H H
391 C2H5 H CH3 CHZSCH3 H H
392 C2H5 H F CH2SCH3 H H
3AfiC2H5 H CI CH2SCH3 H H
394 CpHg H Br CH2SCH3 H H
"""' 3A5 C2H5 H CH3 CH2NMe2 H H
3A6 CZHS H F CH2NMe2 H H
397 C2H5 H CI CH2NMe2 H H
3AE C2H5 H Br CH2NMe2 H H
398 C2H5 H CI CH3 H H
400 C2H5 H Br CH3 H H
401 C2H5 H F CH3 H H
CA 02386800 2002-04-05
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Table 3: Compounds of the formula (3)
H3C CH3
R4 R5
N ~ N R3
R6 (3)
H2N N N
H o8
No. R3 R4 R5 Rs R' Re Phys.
" data
402 CH3 CH3 H F H H
403 CH3 CF3 H F H H Oil
404 CH3 OH H F H H
405 CH3 OCH3 H F H H
406 CH3 i-Pr2 H CH2CeH5 H H
407 CH3 F H F H H Oil
408 CH3 CI H F H H
409 CH3 Br H F H H
,,,.", 410 CH3 I H C(CH3)3 H H
411 CH3 CH3 H OCHZCBHS H H
412 CH3 CF3 H OCBHS H H
413 CH3 OH H NOZ H H Resin
414 CH3 OCH3 H NHz H H Resin
415 CH3 CH20Me CsHS H H
' H
416 CH3 F H NHCOCH3 H H Resin
417 CH3 CI H NHCHO H H Resin
418 CH3 Br I H N(S02Me)2H H Resin
~
419 CH3 I ; H NHS02CH3 H H Resin
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No. R3 R4 R5 R6 R' Re Phys.
data
420 CH3 CH3 H SCH3 H H
421 CH3 CF3 H SOCH3 H H
422 CH3 OH H S02NH2 H H
423 CH3 OCH3 H S02NHCH3 H H
424 CH3 CH20Me H F H H
425 CH3 F H S02CH3 H H
426 CH3 CI H CH20CH3 H H
427 CH3 Br H CH2NMe2 H H
42B CH3 1 H CHzSCH3 H H
429 CH3 CH3 H F H H
430 CH3 CF3 H CI H H
431 CH3 CH2NMe2 H F H H
432 CH3 CH2SMe H F H H
433 CH3 CH3 F H H H
434 CH3 CF3 F H H H
435 CH3 F CF3 H H H
~ 436 CH3 CH3 H H CH3 H
437 CH3 CF3 H H CH20CH3 H
438 CH3 OH H H CF3 H
439 CH3 OCH3 H H OCH3 H
440 CH3 CH20Me H H N(CH3)2 H Resin
441 CH3 F H H F H
442 CH3 CI H H CI H
443 CH3 Br H H SOZCH3 H
444 CH3 I H H S02CH3 H
445 CH3 CH3 H H H F
CA 02386800 2002-04-05
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No. R3 R4 R5 R6 R' R$ Phys.
data
446 CH3 CF3 H H H F
447 CH3 H CH3 CI H H Oil
448 CH3 H CF3 F H H
449 CH3 H CH3 F H H Oil
450 CH3 H OCH3 F H H 112
451 CH3 H N02 F H H
452 CH3 H NH2 F H H Oil
453 CH3 H N(CH3)2 F H H
454 CH3 H NHCOCH3 F H H
456 CH3 H NHCHO F H H
456 CH3 H N(S02Me)2F H H
457 CH3 H NHS02CH3 F H H
458 CH3 H SMe F H H
45g CH3 H SOMe F H H
460 CH3 H S02NH2 F H H
461 CH3 H S02NHCH3 F H H
'~'~ 462 CH3 H S02NMe2 F H H
463 CH3 H S02CH3 F H H
464 CH3 H NHCOCH3 S02NH2 H H
466 CH3 H CH20CH3 F H H
466 CH3 H CH2NMe2 F H H
467 CH3 H CH2SCH3 F H H
46B CH3 H F F H H Oil
469 CH3 H CI F H H
470 CH3 H Br F H H Oil
471 CH3 H I F H H
CA 02386800 2002-04-05
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No. R3 R4 RS Rs R' Re Phys.
data
472 CH3 H F c-Pr H H Resin
473 CH3 H F Bzl H H Resin
474 CH3 H F CH=CHZ H H Resin
4~ CH3 H F C---CH H H Resin
476 CH3 H F H F H Oil
477 CH3 F H CI F H Oil
47g CHFMe H OMe Br H H Resin
' 47g CHFMe H Me Br H H Resin
480 CHFMe H N02 Br H H Resin
CHFMe H NH2 Br H H Resin
482 CHFMe H NOz CI H H Resin
483 CHFMe H NH2 CI H H Resin
484 CHFMe H OMe F H H Resin
485 CHFMe H N02 F H H Resin
CHFMe H NH2 F H H Resin
487 CHFMe OMe H F H H Resin
,.~.. a~g CHFMe F H F H H Resin
489 CHFMe F H H H F Resin
490 CHFMe H F H F H Resin
491 CHFMe H F F H H Resin
492 CHFMe H Me F H H Resin
qg3 CH3 H F CI H H Resin
494 CH3 H CH3 H NOZ H Resin
495 CH3 H CF3 H NH2 H Resin
496 CH3 H OH H N(CH3)2 H Resin
497 CH3 H OCH3 H NHCOCH3 H Resin
CA 02386800 2002-04-05
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data
498 CH3 H N02 H NHCHO H Resin
499 CH3 H NH2 H N(S02Me)2H Resin
500 CH3 H N(CH3)2 H NHS02Me H Resin
501 CH3 H NHCOCH3 H F H
502 CH3 H NHCHO H CI H
503 CH3 H N(S02Me)2H Br H
504 CH3 H NHS02CH3 H I H
505 CH3 H SCH3 H CH3 H
506 CH3 H SOCH3 H CF3 H
507 CH3 H S02NH2 H OH H
508 CH3 H S02NHCH3 H OCH3 H
509 CH3 H S02NMez H SCH3 H
510 CH3 H S02CH3 H SOCH3 H
511 CH3 H CH20CH3 H S02NH2 H
512 CH3 H F H S02NHMe H
513 CH3 H CI H S02NMe2 H
'~ 514 CH3 H Br H S02CH3 H
515 CH3 H I H C2H5 H
516 CH3 CH3 CH3 CI H H
517 CH3 CH3 F H CI H
518 CH3 OCH3 CI H F H
519 CH3 OCH3 CH3 H H F
520 CH3 CI H F H CI
521 CH3 H F F F H
522 CH3 CI H F OCH3 H
523 CH3 F H CI OCH3 H
CA 02386800 2002-04-05
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No. R3 R4 R5 R6 R' R8 Phys.
data
524 CH3 F H F F H Oil
525 CH3 F CH3 H CH3 F
526 CH3 F F CI CH3 H
527 CH3 CH3 F CI H F
528 CH3 CH3 F F F CH3
529 CH3 CH3 H CH3 H H
530 CH3 H F CH3 H H
531 CH3 CH3 H CI H H
532 CH3 H -(CH2)4- H H Resin
533 CH3 H CI H CH=CHEt H
534 CH3 H CI H C =CEt H
535 CH3 H CI H CsHs H
536 CH3 H CI H CN H
537 CH3 H CI -(CHZ)a- H
538 CH3 H CI -O(CH2)20- H
539 CH3 H CI -OCH20- H
"' 540 C2H5 CH3 H CH3 H H
541 C2H5 F H CH3 H H
542 CZH5 CH3 H CI H H Resin
543 C2H5 H N(CH3)2 CI H H Resin
544 C2H5 H S02CH3 CH3 H H Resin
545 Me H Me Br H H
546 Me H Me I H H
547 Et H Me F H H fiesin
548 Et H Me CI H H
549 Et H Me Br H H
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No. R3 R4 R5 R6 R' R8 Phys.
data
560 Et H Me 1 H H
C~I-i5 H F F H H Resin
562 C~I-IS H F H F H Resin
c-Pr H OMe Br H H Resin
c-Pr H Me Br H H Resin
c-Pr H N02 Br H H Resin
c-Pr H NH2 Br H H Resin
557 c-Pr H N02 CI H H Resin
c-Pr H NH2 CI H H Resin
c-Pr H OMe F H H Resin
c-Pr H N02 F H H Resin
c-Pr H NH2 F H H Resin
c-Pr OMe H F H H Resin
c-Pr F H F H H Resin
c-Pr F H H H F Resin
c-Pr H Me F H H Resin
~""w ~ c-Pr H F F H H Resin
c-Pr H F H F H Resin
568 Me H Me CH20CH3 H H
569 Me H F CHZOCH3 H H
51n Me H CI CH20CH3 H H
571 Me H Br CH20CH3 H H
6T2 Me H CH3 CH2SCH3 H H
573 Me H F CH2SCH3 H H
574 Me H CI CH2SCH3 H H
575 Me H Br CH2SCH3 H H
CA 02386800 2002-04-05
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No. R3 R4 R5 R6 R' R8 Phys.
data
576 Me H CH3 CHZNMe2 H H
5?T Me H F CH2NMe2 H H
578 Me H CI CH2NMe2 H H
579 Me H Br CHZNMe2 H H
590 Me H CI CH3 H H
5s1 Me H Br CH3 H H
582 C2H5 H CH3 CH20CH3 H H
"~ 583 C2H5 H F CH20CH3 H H
584 C2H5 H CI CHZOCH3 H H
585 C2H5 H Br CH20CH3 H H
586 C2H5 H CH3 CH2SCH3 H H
587 C2H5 H F CH2SCH3 H H
588 CZH5 H CI CH2SCH3 H H
589 CZHS H Br CH2SCH3 H H
56o CZHS H CH3 CH2NMe2 H H
591 CZHS H F CHZNMe2 H H
"""' See C2H5 H CI CHZNMe2 H H
5A3 C2H5 H Br CH2NMe2 H H
5A4 CZH5 H CI CH3 H H
595 C2H5 H Br CH3 H H
yes CZHS H F CH3 H H
CA 02386800 2002-04-05
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Table 4: Compounds of the formula (4)
F CH3
R4 R5
N ~ N R3
R6 (4)
H2N N N
H o s R7
_ Rs R4 - R5 Rs R' Ra Phys.
No. data
597 CH3 CH3 H F H H
5A8 CH3 CF3 H F H H 117
599 CH3 OH H F H H
600 CH3 OCH3 H F H H Oil
601 CH3 i-Pr H CHzCeHS H H
60r2 CH3 F H F H H Oil
603 H CI H F H H 161
604 H H CI F H H 125
605 H H F F H H 127
606 H H CI CI H H 115
607 CH3 CH3 H OCH2CeH5 H H
608 CH3 CF3 H OCsHS H H
609 CH3 OH H NOZ H H Resin
610 CH3 OCH3 H NHZ H H Resin
611 CH3 CHZOMe H CsHS H H
612 CH3 F H NHCOCH3 H H Resin
613 CH3 CI H NHCHO H H Resin
614 CH3 Br H N(SOZCH3)2H H Resin
CA 02386800 2002-04-05
No. R3 R4 RS R6 R' R8 Phys.
data
615 CH3 I H NHS02CH3 H H Resin
616 CH3 CH3 H SCH3 H H
617 CH3 CF3 H SOCH3 H H
618 CH3 OH H S02NH2 H H
619 CH3 OCH3 H S02NHCH3 H H
620 CH3 CH20Me H F H H
621 CH3 F H S02CH3 H H
622 CH3 CI H CH20CH3 H H
6zi CH3 Br H CH2N(CH3)2H H
624 CH3 I H CHzSCH3 H H
625 CH3 CH3 H F H H
626 CH3 CF3 H CI H H
627 CH3 CH2NMe2 H F H H
628 CH3 CHZSMe H F H H
629 CH3 CH3 F H H H
630 CH3 CF3 F H H H
'"'"' 631 CH3 F CF3 H H H
632 CH3 CH3 H H CH3 H
633 CH3 CF3 H H CH20CH3 H
634 CH3 OH H H CF3 H
636 CH3 OCH3 H H OCH3 H
636 CH3 CH20Me H H N(CH3)2 H Resin
637 CH3 F H H F H
638 CH3 CI H H CI H
639 CH3 Br H H S02CH3 H
640 CH3 I H H S02CH3 H
CA 02386800 2002-04-05
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No. R3 R4 RS R6 R' RB Phys.
data
641 CH3 CH3 H H H F
642 CH3 CF3 H H H F
643 CH3 H CH3 CI H H Oil
644 CH3 H CF3 F H H
645 CH3 H CH3 F H H 112
646 CH3 H OCH3 F H H 60
647 CH3 H N02 F H H
'~ 648 CH3 H NH2 F H H Oil
649 CH3 H N(CH3)2 F H H
660 CH3 H NHCOCH3 F H H
661 CH3 H NHCHO F H H
662 CH3 H N(SOZCH3)2F H H
663 CH3 H NHS02CH3 F H H
664 CH3 H SCH3 F H H
666 CH3 H SOCH3 F H H
666 CH3 H S02NH2 F H H
667 CH3 H S02NHCH3 F H H
668 CH3 H S02N(CH3)2F H H
CH3 H S02CH3 F H H
CH3 H NHCOCH3 S02NH2 H H
661 CH3 H CH20CH3 F H H
662 CH3 H CH2N(CH3)2F H H
663 CH3 H CH2SCH3 F H H
664 CH3 H F F H H 111
666 CH3 H CI F H H Oil
666 CH3 H Br F H H 61
CA 02386800 2002-04-05
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No. R3 R4 R5 Rs R' RB Phys.
data
667 CH3 H I F H H
Egg CH3 H F c-Pr H H Resin
Egg CH3 H F Bzl H H Resin
67p CH3 H F CH=CH2 H H Resin
671 CH3 H F C---CH H H Resin
CH3 H F H F H Oil
g73 CH3 F H CI F H Oil
_
674 CHFMe H OMe Br H H Resin
CHFMe H Me Br H H Resin
CHFMe H N02 Br H H Resin
677 CHFMe H NH2 Br H H Resin
67g CHFMe H N02 CI H H Resin
CHFMe H NH2 CI H H Resin
CHFMe H OMe F H H Resin
CHFMe H N02 F H H Resin
682 CHFMe H NH2 F H H Resin
"" 683 CHFMe OMe H F H H Resin
CHFMe F H F H H Resin
686 CHFMe F H H H F Resin
Egg CHFMe H F H F H Resin
687 CHFMe H F F H H Resin
CHFMe H Me F H H Resin
Egg CH3 H F CI H H Resin
690 CH3 H CH3 H N02 H Resin
CH3 H CF3 H NHz H Resin
692 CH3 H OH H N(CH3)2 H Resin
CA 02386800 2002-04-05
83
No. R3 R4 R5 R6 R' Rg Phys.
data
6g3 CH3 H OCH3 H NHCOCH3 H Resin
6A4 CH3 H N02 H NHCHO H Resin
6A5 CH3 H NH2 H N(S02CH3)2H Resin
696 CH3 H N(CH3)2 H NHS02CH3 H Resin
697 CH3 H NHCOCH3 H F H
698 CH3 H NHCHO H CI H
6A9 CH3 H N(S02CH3)2H Br H
700 CH3 H NHS02CH3 H I H
701 CH3 H SCH3 H CH3 H
7U2 CH3 H SOCH3 H CF3 H
70Ci CH3 H S02NH2 H OH H
704 CH3 H S02NHCH3 H OCH3 H
706 CH3 H SOZN(CH3)2H SCH3 H
706 CH3 H S02CH3 H SOCH3 H
707 CH3 H CH20CH3 H S02NH2 H
708 CH3 H F H S02NHCH3 H
'"~ 709 CH3 H CI H S02N(CH3)2H
710 CH3 H Br H S02CH3 H
711 CH3 H I H C2H5 H
712 CH3 CH3 CH3 CI H H
713 CH3 CH3 F H CI H
714 CH3 OCH3 CI H F H Oil
715 CH3 OCH3 CH3 H H F
716 CH3 CI H F H CI
717 CH3 H F F F H 51
718 CH3 CI H ~ F OCH3 H Oil
CA 02386800 2002-04-05
84
No. R3 R4 RS R6 R' Re Phys.
data
719 CH3 F H CI OCH3 H
72a CH3 F H F F H
721 CH3 F CH3 H CHI F
7?2 CH3 F F CI CHI H
723 CH3 CH3 F CI H F
724 CH3 CH3 F F F CH3
725 CH3 CH3 H CH3 H H
726 CH3 H F CH3 H H
727 CH3 CH3 H CI H H
728 CH3 H CI H CH=CHEt H
729 CH3 H CI H C =CEt H
730 CH3 H CI H CsHS H
731 CH3 H CI H CN H
732 CH3 H CI -(CH2)4- H
733 CH3 H CI -O(CH2)20- H
734 CH3 H CI -OCH20- H
"~ 735 Et CH3 H CH3 H H
736 Et F H CH3 H H
737 Et CH3 H CI H H
738 Et H N(CH3)2 CI H H Resin
739 Et H S02CH3 CH3 H H
740 Me H Me Br H H
741 Me H Me I H H
742 Et H Me F H H Resin
743 Et H Me CI H H
744 Et H Me Br H H
CA 02386800 2002-04-05
No. R3 R4 RS Rs R' R8 Phys.
data
745 Et H Me I H H
746 C~I-IS H F F H H Resin
747 C~I-15 H F H F H Resin
748 c-Pr H OMe Br H H Resin
749 c-Pr H Me Br H H Resin
750 c-Pr H N02 Br H H Resin
751 c-Pr H NH2 Br H H Resin
"~ 752 c-Pr H N02 CI H H Resin
753 c-Pr H NH2 CI H H Resin
'754 c-Pr H OMe F H H Resin
756 c-Pr H N02 F H H Resin
756 c-Pr H NH2 F H H Resin
757 c-Pr OMe H F H H Resin
758 c-Pr F H F H H Resin
7gg c-Pr F H H H F Resin
760 c-Pr H Me F H H Resin
761 c-Pr H F F H H Resin
762 c-Pr H F H F H Resin
763 Me H Me CH20CH3 H H
764 Me H F CH20CH3 H H
766 Me H CI CH20CH3 H H
766 Me H Br CH20CH3 H H
767 Me H CH3 CH2SCH3 H H
768 Me H F CH2SCH3 H H
769 Me H CI CH2SCH3 H H
770 Me H Br CH2SCH3 H H
CA 02386800 2002-04-05
86
No. R3 R4 R5 R6 R' RB Phys.
data
771 Me H CH3 CH2N(CH3)2H H
772 Me H F CH2N(CH3)2H H
773 Me H CI CH2N(CH3)2H H
774 Me H Br CH2N(CH3)2H H
775 Me H CI CH3 H H
776 Me H Br CH3 H H
777 Et H CH3 CH20CH3 H H
778 Et H F CH20CH3 H H
779 Et H CI CH20CH3 H H
780 Et H Br CH20CH3 H H
781 Et H CH3 CH2SCH3 H H
782 Et H F CH2SCH3 H H
783 Et H CI CH2SCH3 H H
784 Et H Br CH2SCH3 H H
786 Et H CH3 CHzN(CH3)ZH H
786 Et H F CH2N(CH3)2H H
''~ 787 Et H CI CH2N(CH3)2H H
788 Et H Br CHZN(CH3)2H H
789 Et H CI CH3 H H
790 Et H Br CH3 H H
T91 Et H F CH3 H H
CA 02386800 2002-04-05
87
Table 5: Compounds of the formula (5)
CH3
F
R4 R5
N ~ N R3
R 6 (5)
H2N N
H Rg
No. R3 R R5 R6 R' RS Phys.
,,~" data
792 CH3 CH3 H F H H
79a CH3 CF3 H F H H 68
794 CH3 OH H F H H
796 CH3 OCH3 H F H H Oil
796 CH3 i-Pr H CH2CsH5 H H
797 CH3 F H F H H
798 CH3 CI H F H H
799 CH3 Br H F H H
800 CH3 I H C(CH3)3 H H
ern CH3 CH3 H OCH2C6H5 H H
802 CH3 CF3 H OCsHS H H
80(3 CH3 OH H N02 H H
804 CH3 OCH3 H NH2 H H
805 CH3 CH20Me H C6H5 H H
806 CH3 F H NHCOCH3 H H
807 CH3 CI H NHCHO H H
808 CH3 Br H N(S02Me)2 H H
809 CH3 1 H NHS02CH3 H H
CA 02386800 2002-04-05
88
No. R3 R RS Rs R' R8 Phys.
data
810 CH3 CH3 H SCH3 H H
811 CH3 CF3 H SOCH3 H H
812 CH3 OH H S02NH2 H H
813 CH3 OCH3 H S02NHCH3H H
814 CH3 CHZOMe H F H H
815 CH3 F H S02CH3 H H
816 CH3 CI H CHZOCH3 H H
817 CH3 Br H CH2NMeZ H H
818 CH3 I H CH2SCH3 H H
819 CH3 CH3 H F H H
880 CH3 CF3 H CI H H
821 CH3 CHZNMe2 H F H H
822 CH3 CH2SMe H F H H
82<i CH3 CH3 F H H H
824 CH3 CF3 F H H H
825 CH3 F CF3 H H H
-
" 826 CH3 CH3 H H CH3 H
827 CH3 CF3 H H CH20CH3 H
828 CH3 OH H H CF3 H
829 CH3 OCH3 H H OCH3 H
830 CH3 CH20Me H H N(CH3)2 H Resin
831 CH3 F H H F H
832 CH3 CI H H CI H
833 CH3 Br H H S02CH3 H
834 CH3 I H H S02CH3 H
836 CH3 CH3 H H H F
CA 02386800 2002-04-05
89
No. R3 R4 RS R6 R' Re Phys.
data
836 CH3 CF3 H H H F
837 CH3 H CH3 CI H H
838 CH3 H CF3 F H H
839 CH3 H CH3 F H H 44
840 CH3 H OCH3 F H H Oil
841 CH3 H N02 F H H
842 CH3 H NH2 F H H Oil
843 CH3 H N(CH3)2 F H H
844 CH3 H NHCOCH3 F H H
845 CH3 H NHCHO F H H
846 CH3 H N(S02Me)2F H H
847 CH3 H NHS02CH3 F H H
848 CH3 H SCH3 F H H
849 CH3 H SOCH3 F H H
860 CH3 H SOZNH2 F H H
851 CH3 H S02NHCH3 F H H
852 CH3 H S02NMe2 F H H
85,3 CH3 H S02CH3 F H H
864 CH3 H NHCOCH3 S02NH2 H H
856 CH3 H CH20CH3 F H H
856 CH3 H CH2NMe2 F H H
CH3 H CHZSCH3 F H H
858 CH3 H F F H H
869 CH3 H CI F H H Oil
860 CH3 H Br F H H 62
861 CH3 H I F H H
CA 02386800 2002-04-05
No. R3 R4 R5 R6 R' R8 Phys.
data
862 CH3 H F c-Pr H H Resin
863 CH3 H F Bzl H H Resin
864 CH3 H F CH=CH2 H H Resin
866 CH3 H F C---CH H H Resin
866 CH3 H F H F H Oil
867 CH3 F H CI F H Oil
,....
868 CFHMe H OMe Br H H Resin
869 CFHMe H Me Br H H Resin
8710 CFHMe H N02 Br H H Resin
87~ CFHMe H NH2 Br H H Resin
872 CFHMe H N02 CI H H Resin
873 CFHMe H NH2 CI H H Resin
874 CFHMe H OMe F H H Resin
875 CFHMe H NO2 F H H Resin
876 CFHMe H NH2 F H H Resin
877 CFHMe OMe H F H H Resin
878 CFHMe F H F H H Resin
879 CFHMe F H H H F Resin
880 CFHMe H F H F H Resin
881 CFHMe H F F H H Resin
882 CFHMe H Me F H H Resin
883 CH3 H F CI H H Resin
884 CH3 H CH3 H N02 H Resin
8~ CH3 H CF3 H NH2 H Resin
886 CH3 H OH H N(CH3)2 H Resin
887 CH3 H OCH3 H NHCOCH3 H Resin
CA 02386800 2002-04-05
91
No. R3 R4 RS R6 R' R$ Phys.
data
888 CH3 H N02 H NHCHO H Resin
889 CH3 H NH2 H N(S02CH3)2H Resin
880 CH3 H N(CH3)2 H NHS02CH3 H Resin
891 CH3 H NHCOCH3 H F H
892 CH3 H NHCHO H CI H
89Ci CH3 H N(S02Me)2H Br H
~4 CH3 H NHS02CH3 H I H
895 CH3 H SCH3 H CH3 H
896 CH3 H SOCH3 H CF3 H
897 CH3 H S02NH2 H OH H
eAB CH3 H S02NHCH3 H OCH3 H
CH3 H SOZNMe2 H SCH3 H
90o CH3 H S02CH3 H SOCH3 H
901 CH3 H CHZOCH3 H S02NH2 H
902 CH3 H F H S02NHCH3 H
903 CH3 H CI H S02N(CH3)ZH
904 CH3 H Br H S02CH3 H
905 CH3 H I H C2H5 H
906 CH3 CH3 CH3 CI H H
907 CH3 CH3 F H CI H
908 CH3 OCH3 CI H F H 100
909 CH3 OCH3 CH3 H H F
910 CH3 CI H F H CI
911 CH3 H F F F H 60
912 CH3 CI H F OCH3 H
913 CH3 F H CI OCH3 H
CA 02386800 2002-04-05
92
No. R3 R4 RS R6 R' R$ Phys.
data
914 CH3 F H F F H
915 CH3 F CH3 H CH3 F
916 CH3 F F CI CH3 H
917 CH3 CH3 F CI H F
918 CH3 CH3 F F F CH3
919 CH3 CH3 H CH3 H H
920 CH3 H F CH3 H H
9121 CH3 CH3 H CI H H
922 CH3 H CI H CH=CHet H
92;3 CH3 H CI H C =CEt H
9p4 CH3 H CI H C6H5 H
9~i CH3 H CI H CN H
926 CH3 H CI -(CH2)4- H
9127 CH3 H CI -O(CH2}20- H
928 CH3 H CI -OCH20- H Resin
9129 C2H5 CH3 H CH3 H H
930 C2H5 F H CH3 H H
931 CzHs CH3 H CI H H
902 CZHS H N(CH3)2 CI H H
93;i C2H5 H SOZCH3 CH3 H H
934 Me H Me Br H H
936 Me H Me I H H
906 Et H Me F H H Resin
937 Et H Me CI H H
938 Et H Me Br H H
939 Et H Me I H H
CA 02386800 2002-04-05
93
No. R3 R4 RS Rs R' R8 Phys.
data
940 C~I-IS H F F H H Resin
941 CzHS H F H F H Resin
942 c-Pr H OMe Br H H Resin
943 c-Pr H Me Br H H Resin
944 c-Pr H N02 Br H H Resin
945 c-Pr H NH2 Br H H Resin
946 c-Pr H N02 CI H H Resin
947 c-Pr H NH2 Cl H H Resin
948 c-Pr H OMe F H H Resin
949 c-Pr H N02 F H H Resin
950 c-Pr H NHZ F H H Resin
951 c-Pr OMe H F H H Resin
952 c-Pr F H F H H Resin
953 c-Pr F H H H F Resin
954 c-Pr H Me F H H Resin
955 c-Pr H F F H H Resin
956 c-Pr H F H F H Resin
957 Me H Me CH20CH3 H H
968 Me H F CH20CH3 H H
959 Me H CI CH20CH3 H H
960 Me H Br CH20CH3 H H
961 Me H CH3 CHZSCH3 H H
962 Me H F CH2SCH3 H H
963 Me H CI CH2SCH3 H H
964 Me H Br CH2SCH3 H H
966 Me H CH3 CH2NMe2 H H
CA 02386800 2002-04-05
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No. R3 R' R5 R6 R' R8 Phys.
data
966 Me H F CH2NMe2 H H
967 Me H CI CH2NMez H H
968 Me H Br CH2NMe2 H H
968 Et H CI CH3 H H
970 Me H Br CH3 H H
9r71 Et H CH3 CH20CH3 H H
972 Et H F CH20CH3 H H
9T3 Et H CI CH20CH3 H H
974 Et H Br CH20CH3 H H
975 Et H CH3 CH2SCH3 H H
976 Et H F CH2SCH3 H H
977 Et H CI CH2SCH3 H H
978 Et H Br CH2SCH3 H H
979 Et H CH3 CH2NMe2 H H
980 Et H F CH2NMe2 H H
981 Et H CI CH2NMe2 H H
982 Et H Br CH2NMe2 H H
983 Et H CI CH3 H H
984 Et H Br CH3 H H
98,5 Et H F CH3 H H
CA 02386800 2002-04-05
Table 6: Compounds of the formula (6)
CH3
F
CH3 R4 R5
N ~ N R3
H N' _N' _ R6 (6)
N
No. R3 R4 R5 R6 R' R8 Phys.
data
996 CH3 CH3 H F H H
987 CH3 CF3 H F H H 179
988 CH3 OH H F H H
989 CH3 OCH3 H F H H Oil
990 CH3 i-Pr H CHZCBHS H H
991 CH3 F H F H H Oil
992 CH3 CI H F H H
99;i CH3 Br H F H H
~"' 994 CH3 I H C(CH3)3 H H
l
985 CH3 CH3 H OCHZC6H5 H H
996 CH3 CF3 H OC6H5 H H
997 CH3 OH H NOZ H H Resin
998 CH3 OCH3 H NHZ H H Resin
999 CH3 CHZOMe H C6H5 H H
1000 CH3 F H NHCOCH3 H H Resin
I
1001 CH3 CI H NHCHO H H Resin
1002 CH3 Br H N(S02Me)2H H Resin
1003 CH3 I H NHS02CH3 H H Resin
CA 02386800 2002-04-05
96
No. R3 R4 R5 R6 R' Re Phys.
data
1004 CH3 CH3 H SCH3 H H
1005 CH3 CF3 H SOCH3 H H
1006 CH3 OH H S02NH2 H H
1007 CH3 OCH3 H S02NHCH3 H H
1008 CH3 CH20Me H F H H
1009 CH3 F H S02CH3 H H
1010 CH3 CI H CH20CH3 H H
1011 CH3 Br H CH2NMe2 H H
1012 CH3 I H CH2SCH3 H H
1013 CH3 CH3 H F H H
1014 CH3 CF3 H CI H H
1015 CH3 CH2NMe2 H F H H
1016 CH3 CH2SMe H F H H
1017 CH3 CH3 F H H H
1018 CH3 CF3 F H H H
1019 CH3 F CF3 H H H
100 CH3 CH3 H H CH3 H
1021 CH3 CF3 H H CH20CH3 H
1022 CH3 OH H H CF3 H
1023 CH3 OCH3 H H OCH3 H
10e4 CH3 CH20Me H H N(CH3)2 H Resin
1025 CH3 F H H F H
1026 CH3 CI H H CI H
1027 CH3 Br H H S02CH3 H
1Q28 CH3 I H H S02CH3 H
1029 CH3 CH3 H H H F
CA 02386800 2002-04-05
97
No. R3 R RS Rs R' R8 Phys.
data
1030 CH3 CF3 H H H F
1031 CH3 H CH3 CI H H 138
1032 CH3 H CF3 F H H
1033 CH3 H CH3 F H H Oil
1034 CH3 H OCH3 F H H Oil
1036 CH3 H N02 F H H
1036 CH3 H NH2 F H H Oil
1037 CH3 H N(CH3)2 F H H
1038 CH3 H NHCOCH3 F H H
1039 CH3 H NHCHO F H H
1040 CH3 H N(S02Me)2F H H
1041 CH3 H NHS02CH3 F H H
1042 CH3 H SMe F H H
1043 CH3 H SOMe F H H
1044 CH3 H S02NH2 F H H
1045 CH3 H S02NHCH3 F H H
1046 CH3 H S02NMe2 F H H
1047 CH3 H S02CH3 F H H
1048 CH3 H NHCOCH3 S02NH2 H H
1049 CH3 H CH20CH3 F H H
1050 CH3 H CH2NMe2 F H H
1061 CH3 H CH2SCH3 F H H
1062 CH3 H F F H H 120
1053 CH3 H CI F H H Oil
1064 CH3 H Br F H H 132
1056 CH3 H I F H H
CA 02386800 2002-04-05
98
No. R3 R R5 R6 R' Re Phys.
data
X056 CH3 H F c-Pr H H Resin
1057 CH3 H F CHzC6H5 H H Resin
X058 CH3 H F CH=CH2 H H Resin
CH3 H F C---CH H H Resin
1060 CH3 H F H F H 143
1061 CH3 F H CI F H 130
1062 CHFMe H OMe Br H H Resin
1063 CHFMe H Me . Br H H Resin
1064 CHFMe H N02 Br H H Resin
1066 CHFMe H NH2 Br H H Resin
1066 CHFMe H N02 CI H H Resin
1067 CHFMe H NH2 CI H H Resin
1068 CHFMe H OMe F H H Resin
1069 CHFMe H N02 F H H Resin
1070 CHFMe H NHZ F H H Resin
1071 CHFMe OMe H F H H flesin
~0'T2 CHFMe F H F H H Resin
1073 CHFMe F H H H F Resin
1074 CHFMe H F H F H Resin
t075 CHFMe H F F H H Resin
1076 CHFMe H Me F H H Resin
1077 CH3 H F CI H H Resin
1078 CH3 H CH3 H N02 H Resin
CH3 H CF3 H NH2 H Resin
1060 CH3 H OH H N(CH3)2 H Resin
CH3 H OCH3 H NHCOCH3 H Resin
CA 02386800 2002-04-05
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No. R3 R4 RS R6 R' RB Phys.
data
1082 CH3 H NOZ H NHCHO H Resin
1083 CH3 H NH2 H N(S02Me)2H Resin
1084 CH3 H N(CH3)2 H NHS02CH3 H Resin
1086 CH3 H NHCOCH3 H F H
1096 CH3 H NHCHO H CI H
1087 CH3 H N(S02Me)2H Br H
1088 CH3 H NHS02CH3 H I H
1089 CH3 H SMe H ~ CH3 H
1090 CH3 H SOMe H CF3 H
1091 CH3 H S02NH2 H OH H
1092 CH3 H SOZNHCH3 H OCH3 H
1093 CH3 H SOZNMe2 H SCH3 H
109~t CH3 H S02CH3 H SOCH3 H
1095 CH3 H CH20CH3 H S02NH2 H
1096 CH3 H F H S02NHCH3 H
1097 CH3 H CI H S02NMe2 H
loeB CH3 H Br H SOZCH3 H
1099 CH3 H I H C~HS H
1100 CH3 CH3 CH3 CI H H
1101 CH3 CH3 F H CI H
11~ CH3 OCH3 CI H F H Oil
1103 CH3 OCH3 CH3 H H F
1104 CH3 CI H F H CI
1105 CH3 H F F F H 129
1106 CH3 CI H F OCH3 H
1107 CH3 F H CI OCH3 H
CA 02386800 2002-04-05
No. R3 R4 R5 Rs R' R8 Phys.
data
1108 CH3 F H F F H 95
1109 CH3 F CH3 H CH3 F
1110 CH3 F F CI CH3 H
1111 CH3 CH3 F CI H F
1112 CH3 CH3 F F F CH3
1113 CH3 CH3 H CH3 H H
1114 CH3 H F CH3 H H
1115 CH3 CH3 H CI H H
1116 H H CI CI H H Resin
1117 CH3 H -(CHZ)3- H H Resin
1118 CH3 H CI H CH=CHEt H
1119 CH3 H CI H C =CEt H
1120 CH3 H CI H CsHs H
1121 CH3 H CI H CN H
1122 CH3 H CI -(CH2)4- H
1123 CH3 H CI -O(CHZ)20- H
1124 CH3 H CI -OCHZO- H
1125 C2H5 CH3 H CH3 H H
1126 C2H5 F H CH3 H H
1127 C2H5 CH3 H CI H H
1128 C2H5 H N(CH3)2 CI H H
1129 C2H5 H S02CH3 CH3 H H
1130 Me H Me Br H H
1131 Me H Me I H H
1132 Et H Me F H H Resin
1133 Et H Me CI H H
CA 02386800 2002-04-05
No. R3 R4 RS R6 R' R8 Phys.
data
1134 E H Me Br H H
Et H Me I H H
1136 C~I-IS H F F H H Resin
1137 CzHS H F H F H Resin
t138 c-Pr H OMe Br H H Resin
1139 c-Pr H Me Br H H Resin
1140 c-Pr H N02 Br H H Resin
1141 c-Pr H NH2 Br H H Resin
1142 c-Pr H N02 CI H H Resin
1143 c-Pr H NH2 CI H H Resin
1144 c-Pr H OMe F H H Resin
1145 c-Pr H N02 F H H Resin
1146 c-Pr H NH2 F H H Resin
1147 c-Pr OMe H F H H Resin
1148 c-Pr F H F H H Resin
1149 c-Pr F H H H F Resin
1150 c-Pr H Me F H H Resin
1151 c-Pr H F F H H Resin
1152 c-Pr H F H F H Resin
1153 Me H Me CH20CH3 H H
1154 Me H F CHZOCH3 H H
1155 Me H CI CH20CH3 H H
1156 Me H Br CHZOCH3 H H
1157 Me H CH3 CH2SCH3 H H
1158 Me H F CH2SCH3 H H
1159 Me H CI CH2SCH3 H H
CA 02386800 2002-04-05
102
No. R3 R4 RS R6 R' R8 Phys.
data
1160 Me H Br CH2SCH3 H H
1161 Me H CH3 CH2NMe2 H H
1162 Me H F CH2NMe2 H H
1163 Me H CI CHZNMe2 H H
1164 Me H Br CH2NMe2 H H
Me H CI CH3 H H
1166 Me H Br CH3 H H
1167 C2H5 H CH3 CH20CH3 H H
1168 C2H5 H F CH20CH3 H H
1168 C2H5 H CI CH20CH3 H H
1170 C2H5 H Br CH20CH3 H H
1171 CZH5 H CH3 CH2SCH3 H H
1172 C2H5 H F CH2SCH3 H H
1173 CZHS H CI CH2SCH3 H H
1174 C2H5 H Br CH2SCH3 H H
1175 C2H5 H CH3 CH2NMe2 H H
1176 CZHS H F CH2NMe2 H H
1177 C2H5 H CI CHZNMe2 H H
1178 C2H5 H Br CH2NMe2 H H
1179 CZH5 H CI CH3 H H
1180 C2H5 H Br CH3 H H
1181 C2H5 H F CH3 H H
CA 02386800 2002-04-05
103
Table 7: Compounds of the formula (7)
R4 R5
N ~ N R3
R6 (7)
H2N N N
R8
No. R3 R4 R5 R6 R' R$ Phys.
'""~' data
1182 CH3 CH3 H F H H Resin
1183 CH3 CF3 H F H H
1184 CH3 OH H F H H
1185 CH3 OCH3 H F H H
1186 CH3 i-Pr H CH2CsH5 H H
1187 CH3 F H F H H
1188 CH3 CI H F H H
.. 1189 CH3 Br H F H H
1190 CH3 I H i-Pr H H
1191 CH3 CH3 H OCH2Ph H H
1192 CH3 CF3 H OPh H H
1193 CH3 OH H NOz H H Resin
1194 CH3 OCH3 H NHZ H H Resin
1195 CH3 CHzOMe H Ph H H
I
1196 CH3 F H NHCOMe H H Resin
1197 CH3 CI H NHCHO H H Resin
1198 CH3 Br H N(S02Me)2H H Resin
~
CA 02386800 2002-04-05
104
No. R3 R4 RS R6 R' RB Phys.
data
1199CH3 I H NHS02Me H H Resin
1200CH3 CH3 H SMe H H
1201CH3 CF3 H SOMe H H
1202CH3 OH H S02NH2 H H
120ciCH3 OCH3 H SOZNHMe H H
1204CH3 CH20Me H F H H
1205CH3 F H SOZCH3 H H
1206CH3 CI H CH20CH3 H H
1207CH3 Br H CH2NMe2 H H
1208CH3 I H CH2SCH3 H H
1209CH3 CH3 H F H H
1210CH3 CF3 H CI H H
1211CH3 CH2NMe2 H F H H
1212CH3 CH2SMe H F H H
1213CH3 CH3 F H H H
1214CH3 CF3 F H H H
1215CH3 F CF3 H H H
1216CH3 CH3 H H CH3 H
1217CH3 CF3 H H CH20CH3 H
1218CH3 OH H H CF3 H
1219CH3 OCH3 H H OCH3 H
1220CH3 CH20Me H H N(CH3)2 H Resin
1221CH3 F H H F H
1222CH3 CI H H CI H
1223CH3 Br H H S02CH3 H
1224CH3 I H H S02CH3 H
CA 02386800 2002-04-05
105
No. R3 R4 RS R6 R' Re Phys.
data
1225 CH3 CH3 H H H F
1226 CH3 CF3 H H H F
1227 CH3 H CH3 CI H H
1228 CH3 H CF3 F H H
1229 CH3 H CH3 F H H
1230 CH3 H OCH3 F H H
1231 CH3 H N02 F H H
1232 CH3 H NH2 F H H
1233 CH3 H N(CH3)2 F H H
1234 CH3 H NHCOCH3 F H H
1236 CH3 H NHCHO F H H
1236 CH3 H N(S02CH3)2F H H
1237 CH3 H NHS02CH3 F H H
1238 CH3 H SMe F H H
1239 CH3 H SOMe F H H
1240 CH3 H SOzNH2 F H H
"~ 1241 CH3 H SOZNHCH3 F H H
1242 CH3 H S02N(CH3)2F H H
1243 CH3 H S02CH3 F H H
1244 CH3 H NHCOCH3 S02NH2 H H
1245 CH3 H CH20CH3 F H H
1246 CH3 H CHZN(CH3)2F H H
1247 CH3 H CH2SCH3 F H H
1248 CH3 H F F H H
1249 CH3 H CI F H H
1250 CH3 H Br F H H
CA 02386800 2002-04-05
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data
1251 CH3 H I F H H
1252 CH3 H F c-Pr H H Resin
1253 CH3 H F CH2CsH5 H H Resin
1254 CH3 H F CH=CH2 H H Resin
1256 CH3 H F C---CH H H Resin
1256 CH3 H F H F H Oil
1257 CH3 F H CI F H Oil
1258 CHFMe H OMe Br H H Resin
1299 CHFMe H Me Br H H Resin
1260 CHFMe H N02 Br H H Resin
1261 CHFMe H NH2 Br H H Resin
1262 CHFMe H N02 CI H H Resin
128'iCHFMe H NH2 CI H H Resin
1264 CHFMe H OMe F H H Resin
1266 CHFMe H N02 F H H Resin
1286 CHFMe H NHZ F H H Resin
1267 CHFMe OMe H F H H Resin
1268 CHFMe F H F H H Resin
1269 CHFMe F H H H F Resin
12'l~CHFMe H F H F H Resin
1271 CHFMe H F F H H Resin
1272 CHFMe H Me F H H Resin
1273 CH3 H F CI H H Resin
1274 CH3 H CH3 H NOZ H Resin
1275 CH3 H CF3 H NH2 H Resin
1276 CH3 H OH H N(CH3)2 H Resin
CA 02386800 2002-04-05
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No. R3 R4 RS R6 R' R8 Phys.
data
1277 CH3 H OCH3 H NHCOCH3 H Resin
1278 CH3 H N02 H NHCHO H Resin
1279 CH3 H NH2 H N(SOZCH3)2 H Resin
1280 CH3 H NMe2 H NHS02CH3 H Resin
1281 CH3 H NHCOCH3 H F H
1282 CH3 H NHCHO H CI H
1283 CH3 H N(S02Me)2 H Br H
1284 CH3 H NHSOzMe H I H
1286 CH3 H SMe H CH3 H
1286 CH3 H SOMe H CF3 H
1257 CH3 H S02NH2 H OH H
1288 CH3 H S02NHMe H OCH3 H
1289 CH3 H S02NMe2 H SCH3 H
1290 CH3 H S02CH3 H SOCH3 H
1291 CH3 H CH20CH3 H S02NH2 H
1292 CH3 H F H SOzNHCH3 H
1293 CH3 H CI H S02N(CH3)2 H
1294 CH3 H Br H S02CH3 H
1295 CH3 H I H C2H5 H
1296 CH3 CH3 CH3 CI H H
1297 CH3 CH3 F H CI H
1298 CH3 OCH3 CI H F H
1299 CH3 OCH3 CH3 H H F
1300 CH3 CI H F H CI
1301 CH3 H F F F H
1302 CH3 CI H F OCH3 H
CA 02386800 2002-04-05
108
No. R3 R4 RS R6 R' Re Phys.
data
1303 CH3 F H CI OCH3 H
1304 CH3 F H F F H
1306 CH3 F CH3 H CH3 F
1306 CH3 F F CI CH3 H
1307 CH3 CH3 F CI H F
1308 CH3 CH3 F F F CH3
1309 CH3 CH3 H CH3 H H
1310 CH3 H F CH3 H H
1311 CH3 CH3 H CI H H
1312 CH3 H CI H GH=CHEt H
1313 CH3 H CI H C =CEt H
1314 CH3 H CI H C6H5 H
1315 CH3 H CI H CN H
1316 CH3 H CI -(CH2)a-
1317 CH3 H CI -O(CH2)20-
1318 CH3 H CI -OCH20-
"w
1319 C2H5 CH3 H CH3 H H Resin
1320 C2H5 F H CH3 H H Resin
1321 C2H5 CH3 H CI H H Resin
1322 C2H5 H N(CH3)2 CI H H Resin
1323 C2H5 H S02CH3 CH3 H H Resin
1324 Me H CHI Br H H
1325 Me H CHI I H H
1326 Et H CHI F H H Resin
1327 Et H CHI CI H H
1328 Et H CHI Br H H
CA 02386800 2002-04-05
109
No. R3 R4 R5 R6 R' R8 Phys.
data
1329 Et H CHI I H H
1330 Et H CH3 CH20CH3 H H
1331 CzFiS H F F H H Resin
1332 C~i-15 H F H F H Resin
1333 c-Pr H OMe Br H H Resin
1334 c-Pr H Me Br H H Resin
1336 c-Pr H N02 Br H H Resin
1336 c-Pr H NH2 Br H H Resin
1337 c-Pr H N02 CI H H Resin
1338 c-Pr H NH2 CI H H Resin
133A c-Pr H OMe F H H Resin
1340 c-Pr H N02 F H H Resin
1341 c-Pr H NH2 F H H Resin
1342 c-Pr OMe H F H H Resin
1343 c-Pr F H F H H Resin
1344 c-Pr F H H H F Resin
'~ X345 c-Pr H Me F H H Resin
1346 c-Pr H F F H H Resin
1347 c-Pr H F H F H Resin
1348 Me H F CH2OCH3 H H
1349 Me H CI CH20CH3 H H
1360 Me H Br CH20CH3 H H
X361 Me H CH3 CH2SCH3 H H
1352 Me H F CHZSCH3 H H
1353 Me H CI CH2SCH3 H H
1364 Me H Br CH2SCH3 H H
CA 02386800 2002-04-05
110
No. R3 R4 RS R6 R7 Re phys.
data
1x56Me H CH3 CH2NMe2 H H
1366Me H F CH2NMe2 H H
1367Me H CI CH2NMe2 H H
1368Me H Br CH2NMe2 H H
1368Me H CI CH3 H H
1360Me H Br CH3 H H
1361C2H5 H CH3 CH20CH3 H H
1362C2H5 H F CH20CH3 H H
1363C2H5 H CI CH20CH3 H H
1364CZHS H Br CH20CH3 H H
1366CZHS H CH3 CH2SCH3 H H
1366C2H5 H F CH2SCH3 H H
1367C2H5 H CI CH2SCH3 H H
1368C2H5 H Br CH2SCH3 H H
1369C2H5 H CH3 CH2NMe2 H H
137DC2H5 H F CHZNMe2 H H
'" 1371C2H5 H CI CH2NMez H H
1372C2H5 H Br CH2NMe2 H H
1373CzHs H CI CH3 H H
1374C2H5 H Br CH3 H H
1375C2H5 H F CH3 H H
CA 02386800 2002-04-05
111
Table 8: Compounds of the formula (8)
F ~ Ra R5
N ~ N R3
R6 ($)
H2N N N
R 8 R7
No. R3 R4 R5 R6 R' R8 Phys.
data
1376 CH3 CH3 H F H H Resin
1377 CH3 CF3 H F H H
1378 CH3 OH H F H H
1379 CH3 OCH3 H F H H
1380 CH3 i-Pr H CH2CgH5 H H
1381 CH3 F H F H H
1382 CH3 CI H F H H
1383 CH3 Br H F H H
'~" 1384 CH3 I H i-Pr H H
1385 CH3 CH3 H OCHZPh H H
1386 CH3 CF3 H OPh H H
1387 CH3 OH H NOZ H H Resin
1388 CH3 OCH3 H NHZ H H Resin
1389 CH3 CH20Me H Ph H H
139o CH3 F H NHCOMe H H Resin
1391 CH3 CI H NHCHO H H Resin
1392 CH3 Br H N(S02Me)2 H H Resin
1393 CH3 I H NHSOZMe H H Resin
~
CA 02386800 2002-04-05
X12
No. R3 R4 R5 R6 R' R8 Phys.
data
1394 CH3 CH3 H SMe H H
1395 CH3 CF3 H SOMe H H
13A6 CH3 OH H SOZNH2 H H
1397 CH3 OCH3 H S02NHMe H H
1398 CH3 CH20Me H F H H
1399 CH3 F H S02CH3 H H
1400 CH3 CI H CH20CH3 H H
1401 CH3 Br H CH2N(CH3)2H H
140p CH3 I H CHZSCH3 H H
140(3CH3 CH3 H F H H
1404 CH3 CF3 H CI H H
1406 CH3 CH2NMe2 H F H H
1406 CH3 CH2SMe H F H H
1407 CH3 CH3 F H H H
1408 CH3 CF3 F H H H
1409 CH3 F CF3 H H H
1410 CH3 CH3 H H CH3 H
1411 CH3 CF3 H H CH20CH3 H
1412 CH3 OH H H CF3 H
1413 CH3 OCH3 H H OCH3 H
1414 CH3 CH20Me H H N(CH3)2 H Resin
1415 CH3 F H H F H
1416 CH3 CI H H CI H
1417 CH3 Br H H S02CH3 H
1418 CH3 I H H S02CH3 H
1419 CH3 CH3 H H H F
CA 02386800 2002-04-05
113
No. R3 R4 RS Rs R' Re Phys.
data
1420 CH3 CF3 H H H F
1421 CH3 H CH3 CI H H
1422 CH3 H CF3 F H H
1423 CH3 H CH3 F H H
1424 CH3 H OCH3 F H H
1425 CH3 H N02 F H H
1426 CH3 H NHZ F H H
..
,
. 1427 CH3 H N(CH3)2 F H H
1428 CH3 H NHCOCH3 F H H
1429 CH3 H NHCHO F H H
1430 CH3 H N(S02CH3)2F H H
1431 CH3 H NHS02CH3 F H H
1432 CH3 H SMe F H H
1433 CH3 H SOMe F H H
1434 CH3 H S02NH2 F H H
1436 CH3 H S02NHCH3 F H H
'~' 1436 CH3 H S02N(CH3)2F H H
1437 CH3 H S02CH3 F H H
1438 CH3 H NHCOCH3 S02NH2 H H
1438 CH3 H CH20CH3 F H H
1440 CH3 H CHZN(CH3)2F H H
1441 CH3 H CH2SCH3 F H H
1442 CH3 H F F H H
1443 CH3 H CI F H H
1444 CH3 H Br F H H
1445 CH3 H I F H H
CA 02386800 2002-04-05
114
No. R3 R4 RS R6 R' Re Phys.
data
1446 CH3 H F c-Pr H H Resin
1447 CH3 H F CH2CsH5 H H Resin
1448 CH3 H F CH=CH2 H H Resin
1449 CH3 H F C---CH H H Resin
1450 CH3 H F H F H Oil
1451 CH3 F H CI F H Oil
1452 CHFMe H OMe Br H H Resin
1453 CHFMe H Me Br H H Resin
1454 CHFMe H N02 Br H H Resin
1456 CHFMe H NH2 Br H H Resin
1456 CHFMe H N02 C1 H H Resin
1457 CHFMe H NHZ CI H H Resin
1458 CHFMe H OMe F H H Resin
1499 CHFMe H N02 F H H Resin
1460 CHFMe H NH2 F H H Resin
1461 CHFMe OMe H F H H Resin
1462 CHFMe F H F H H Resin
1463 CHFMe F H H H F Resin
1464 CHFMe H F H F H Resin
1466 CHFMe H F F H H Resin
1466 CHFMe H Me F H H Resin
1467 CH3 H F CI H H Resin
1468 CH3 H CH3 H N02 H Resin
1469 CH3 H CF3 H NH2 H Resin
X470 CH3 H OH H N(CH3)2 H Resin
1471 CH3 H OCH3 H NHCOCH3 H Resin
CA 02386800 2002-04-05
115
No. R3 R4 R5 R6 R' RB Phys.
data
t472 CH3 H N02 H NHCHO H Resin
1473 CH3 H NH2 H N(SOZCH3)2 H Resin
t474 CH3 H NMe2 H NHS02CH3 H Resin
1475 CH3 H NHCOCH3 H F H
1476 CH3 H NHCHO H CI H
1477 CH3 H N(S02Me)2 H Br H
t478 CH3 H NHS02Me H I H
t479 CH3 H SCH3 H CH3 H
t480 CH3 H SOCH3 H CF3 H
1481 CH3 H S02NH2 H OH H
t482 CH3 H S02NHMe H OCH3 H
1483 CH3 H S02NMe2 H SCH3 H
t484 CH3 H S02CH3 H SOCH3 H
t48,5 CH3 H CH20CH3 H S02NH2 H
t486 CH3 H F H S02NHCH3 H
1487 CH3 H CI H S02N(CH3)2 H
""~ 1488 CH3 H Br H SOZCH3 H
t489 CH3 H I H CzHS H
1490 CH3 CH3 CH3 CI H H
t491 CH3 CH3 F H CI H
1492 CH3 OCH3 CI H F H
t493 CH3 OCH3 CH3 H H F
t494 CH3 CI H F H CI
t495 CH3 H F F F H
t496 CH3 CI H F OCH3 H
1497 CH3 F H CI OCH3 H
CA 02386800 2002-04-05
116
No. R3 R4 RS Rs R' R8 Phys.
data
1498 CH3 F H F F H
1499 CH3 F CH3 H CH3 F
1500 CH3 F F CI CH3 H
1501 CH3 CH3 F CI H F
1502 CH3 CH3 F F F CH3
1503 CH3 CH3 H CH3 H H
1504 CH3 H F CH3 H H
1506 CH3 CH3 H CI H H
1506 CH3 H CI H CH=CHC2H5 H
1507 CH3 H CI H C =CC2H5 H
1508 CH3 H CI H CsHs H
1509 CH3 H CI H CN H
1510 CH3 H CI -(CH2)a-
1511 CH3 H CI -O(CH2)20-
1512 CH3 H CI -OCH20-
1513 C2H5 CH3 H CH3 H H Resin
'""' 1514 C2H5 F H CH3 H H Resin
1515 C2H5 CH3 H CI H H Resin
1516 C2H5 H N(CH3)2 CI H H Resin
1517 C2H5 H S02CH3 CH3 H H Resin
1518 Me H Me Br H H
1519 Me H Me I H H
152D Et H Me F H H Resin
15e1 Et H Me CI H H
1522 Et H Me Br H H
l5zi Et H Me I H H
CA 02386800 2002-04-05
117
No. R3 R4 RS Rs R' Ra Phys.
data
1524 C~I-IS H F F H H Resin
X525 C~I-15 H F H F H Resin
1526 c-Pr H OMe Br H H Resin
1527 c-Pr H Me Br H H Resin
t528 c-Pr H N02 Br H H Resin
t529 c-Pr H NH2 Br H H Resin
1530 c-Pr H N02 CI H H Resin
..,
1531 c-Pr H NH2 CI H H Resin
1532 c-Pr H OMe F H H Resin
1533 c-Pr H NO2 F H H Resin
1534 c-Pr H NH2 F H H Resin
1536 c-Pr OMe H F H H Resin
1536 c-Pr F H F H H Resin
1537 c-Pr F H H H F Resin
1538 c-Pr H Me F H H Resin
1539 c-Pr H F F H H Resin
1540 c-Pr H F H F H Resin
1541 Me H Me CH20CH3 H H
1542 Me H F CH20CH3 H H
1543 Me H CI CH20CH3 H H
1544 Me H Br CH20CH3 H H
1545 Me H CH3 CH2SCH3 H H
1546 Me H F CH2SCH3 H H
1547 Me H CI CH2SCH3 H H
1548 Me H Br CH2SCH3 H H
1549 Me H CH3 CH2N(CH3)2H H
CA 02386800 2002-04-05
118
No. R3 R4 R5 R6 R' RB Phys.
data
1560 Me H F CH2N(CH3)2H H
1561 Me H CL CH2N(CH3)2H H
1562 Me H Br CH2N(CH3)2H H
1563 Me H CI CH3 H H
1564 Me H Br CH3 H H
1556 C2H5 H CH3 CH20CH3 H H
1556 C2H5 H F CH20CH3 H H
1567 C2H5 H CI CH20CH3 H H
1568 C2H5 H Br CH20CH3 H H
156A C2H5 H CH3 CHZSCH3 H H
1560 C2H5 H F CH2SCH3 H H
1561 C2H5 H CI CH2SCH3 H H
1562 CZHS H Br CH2SCH3 H H
1563 C2H5 H CH3 CH2N(CH3)2H H
1564 C2H5 H F CHZN(CH3)2H H
15~ C2H5 H CI CH2N(CH3)2H H
"""~ 1566 C2H5 H Br CH2N(CH3)2H H
1567 C2H5 H CI CH3 H H
1568 C2H5 H Br CH3 H H
X569 C2H5 H F CH3 H H
CA 02386800 2002-04-05
119
Table 9 below refers to the formula (9)
R1
R4 R5
N ~ N R3
R6 (9)
H2N N N
R2 R8 R7
No. R' R2R3 R R5 R6 R' R8 Phys.
data
1570 CF3 H CH3 OCH3 CI H F H 134
1571 CF3 H CH3 CI H F OCH3 H Oil
1572 CF3 H CH3 F H CI OCH3 H
1573 CF3 H CH3 H CH3 OCH3 H H 104
1574 CF3 H CH3 H OCH3 OCH3 H H 163
1575 c-Bu H CH3 H NMe2 CI H H
1576 c-Bu H CH3 H NMe2 S-Me H H
1577 c-Bu H CH3 H CH3 F H H
1578 c-Bu H H H CI H CI H Resin
""""" 1579 c-Pen H CH3 H NMe2 CI H H
1580 c-Pen H CH3 H NMe2 S-Me H H Resin
1581 c-Pen H CH3 H CH3 F H H
1582 c-Hex H CH3 H NMe2 CI H H
1583 c-Hex H CH3 H NMe2 S-Me H H Resin
1584 c-Hex H CH3 H CH3 F H H
1585 CHMe- H CH3 H CH3 OCH3 H H Resin
Ph(4-OH)
1586 t-Bu H CH3 H CH3 OCH3 H H Resin
1587 t-Bu H CH3 H OCH3 OCH3 H H Oil
CA 02386800 2002-04-05
120
No. R' R2 R3 R4 R5 Rs R' R8 Phys.
data
1588 1-Me-c-PrH CH20-(3,5-H CI F H H 128
Me2-Ph)
1589 n-Pen H CH3 H OCH3 OCH3 H H Resin
1580 Bzl H CH3 H OCH3 OCH3 H H Resin
~ ~
Table 10 below refers to the formula (I)
R1
R4 R5
3
N N R
R6 (I)
A N N
R2 R8 R~
No. A R' R2 R3 R4 R5 Re R' R8 Phys.
data
1591 NHZ CH3 CH3 CH3 H SMe H CH3 H
,,... 15A2 NHZ CH3 Ac CH3 H SMe H CH3 H
15ec3NHZ CH3 SOZMe CH3 H SMe H CH3 H
1594 NH2 CH3 c-Pr CH3 H SMe H CH3 H
1595 NHAc CH3 H CH3 H SMe H CH3 H Resin
15A6 NHAc CH3 H CH3 CF3 H SCH3 H H Resin
15A7 NHAc MeCHF H CH3 H OMe Br H H Resin
15A8 NHAc MeCHF H CH3 H Me Br H H Resin
X599 NHAc MeCHF H CH3 H N02 Br H H Resin
1600 NHAc MeCHF H CH3 H NH2 Br H H Resin
1601 NHAc MeCHF H CH3 H N02 CI H H Resin
CA 02386800 2002-04-05
121
No. A R' R2 R3 R4 RS R6 R' R8 Phys.
data
160e NHAc MeCHF H CH3 H NH2 CI H H Resin
l6ociNHAc MeCHF H CH3 H OMe F H H Resin
1604 NHAc MeCHF H CH3 H N02 F H H Resin
1605 NHAc MeCHF H CH3 H NH2 F H H Resin
1606 NHAc MeCHF H CH3 OMe H F H H Resin
1607 NHAc MeCHF H CH3 F H F H H Resin
1608 NHAc MeCHF H CH3 F H H H F Resin
"",,
1609 NHAc MeCHF H CH3 H CH3 F H H Resin
1610 NHAc MeCHF H CH3 H F F H H Resin
1611 NHAc MeCHF H CH3 H F H F H Resin
1612 NHAc EtCHF H CH3 H OMe Br H H Resin
1613 NHAc EtCHF H CH3 H Me Br H H Resin
1614 NHAc EtCHF H CH3 H N02 Br H H Resin
1615 NHAc EtCHF H CH3 H NH2 Br H H Resin
1616 NHAc EtCHF H CH3 H N02 CI H H Resin
1617 NHAc EtCHF H CH3 H NH2 CI H H Resin
"'" 1618 NHAc EtCHF H CH3 H OMe F H H Resin
1619 NHAc EtCHF H CH3 H N02 F H H Resin
lGdO NHAc EtCHF H CH3 H NH2 F H H Resin
1621 NHAc EtCHF H CH3 OMe H F H H Resin
1622 NHAc EtCHF H CH3 F H F H H Resin
162;1NHAc EtCHF H CH3 F H H H F Resin
1624 NHAc EtCHF H CH3 H CH3 F H H Resin
1625 NHAc EtCHF H CH3 H F F H H Resin
1626 NHAc EtCHF H CH3 H F H F H Resin
1627 H2NCONH MeCHF H CH3 H OMe Br H H Resin
CA 02386800 2002-04-05
122
No. A R' R2 R3 R4 R5 R6 R' Rg Phys.
data
1628 H2NCONH MeCHF H CH3 H Me Br H H Resin
1629 H2NCONH MeCHF H CH3 H N02 Br H H Resin
1630 H2NCONH MeCHF H CH3 H NH2 Br H H Resin
1631 H2NCONH MeCHF H CH3 H N02 CI H H Resin
1632 H2NCONH MeCHF H CH3 H NHZ CI H H Resin
1633 H2NCONH MeCHF H CH3 H OMe F H H Resin
1634 H2NCONH MeCHF H CH3 H N02 F H H Resin
1635 H2NCONH MeCHF H CH3 H NH2 F H H Resin
1636 H2NCONH MeCHF H CH3 OMe H F H H Resin
1637 H2NCONH MeCHF H CH3 F H F H H Resin
X638 H2NCONH MeCHF H CH3 F H H H F Resin
1639 H2NCONH MeCHF H CH3 H CH3 F H H Resin
o H2NCONH MeCHF H CH3 H F F H H Resin
1641 H2NCONH MeCHF H CH3 H F H F H Resin
1642 H2NCONH EtCHF H CH3 H OMe Br H H Resin
1643 H2NCONH EtCHF H CH3 H Me Br H H Resin
'~ 1644 H2NCONH EtCHF H CH3 H N02 Br H H Resin
1645 H2NCONH EtCHF H CH3 H NH2 Br H H Resin
1646 H2NCONH EtCHF H CH3 H N02 CI H H Resin
X647 H2NCONH EtCHF H CH3 H NH2 CI H H Resin
1648 H2NCONH EtCHF H CH3 H OMe F H H Resin
1649 H2NCONH EtCHF H CH3 H N02 F H H Resin
1650 H2NCONH EtCHF H CH3 H NH2 F H H Resin
H2NCONH EtCHF H CH3 OMe H F H H Resin
1652 H2NCONH EtCHF H CH3 F H F H H Resin
1663 H2NCONH EtCHF H CH3 F H H H F Resin
CA 02386800 2002-04-05
123
No. A R' R2 R3 R4 RS R6 R' R8 Phys.
data
1664H2NCONH EtCHF H CH3 H CH3 F H H Resin
1665H2NCONH EtCHF H CH3 H F F H H Resin
1666H2NCONH EtCHF H CH3 H F H F H Resin
1667H2NCSNH MeCHF H CH3 H OMe Br H H Resin
1668H2NCSNH MeCHF H CH3 H Me Br H H Resin
166AH2NCSNH MeCHF H CH3 H N02 Br H H Resin
1660H2NCSNH MeCHF H CH3 H NH2 Br H H Resin
1661H2NCSNH MeCHF H CH3 H N02 CI H H Resin
1662H2NCSNH MeCHF H CH3 H NH2 CI H H Resin
X663H2NCSNH MeCHF H CH3 H OMe F H H Resin
1664H2NCSNH MeCHF H CH3 H N02 F H H Resin
16E~H2NCSNH MeCHF H CH3 H NH2 F H H Resin
1666H2NCSNH MeCHF H CH3 OMe H F H H Resin
1667HZNCSNH MeCHF H CH3 F H F H H Resin
1668H2NCSNH MeCHF H CH3 F H H H F Resin
1668H2NCSNH MeCHF H CH3 H CH3 F H H Resin
1670HZNCSNH MeCHF H CH3 H F F H H Resin
1671H2NCSNH MeCHF H CH3 H F H F H Resin
1672HZNCSNH EtCHF H CH3 H OMe Br H H Resin
1673H2NCSNH EtCHF H CH3 H Me Br H H Resin
1674H2NCSNH EtCHF H CH3 H N02 Br H H Resin
1675H2NCSNH EtCHF H CH3 H NH2 Br H H Resin
16716H2NCSNH EtCHF H CH3 H N02 CI H H Resin
1677HZNCSNH EtCHF H CH3 H NH2 CI H H Resin
X678HZNCSNH EtCHF H CH3 H OMe F H H Resin
16T9H2NCSNH EtCHF H CH3 H N02 F H H Resin
CA 02386800 2002-04-05
124
No. A R' R2 R3 R4 RS Rs R' R8 Phys.
data
X680 H2NCSNH EtCHF H CH3 H NH2 F H H Resin
1681 H2NCSNH EtCHF H CH3 OMe H F H H Resin
1682 H2NCSNH EtCHF H CH3 F H F H H Resin
X683 HZNCSNH EtCHF H CH3 F H H H F Resin
1684 H2NCSNH EtCHF H CH3 H CH3 F H H Resin
1685 H2NCSNH EtCHF H CH3 H F F H H Resin
1686 H2NCSNH EtCHF H CH3 H F H F H Resin
1687 NH-S02Me CH3 H CH3 H SMe H CH3 H Resin
X688 NH-S02Me CH3 H CH3 CF3 H SMe H H Resin
166A N=C(Me)OMeCH3 H CH3 CF3 H SMe H H Resin
1680 N=C(Me)OEtCH3 H CH3 CF3 H SMe H H Resin
1691 N=C(Me)SMeCH3 H CH3 CF3 H SMe H H Resin
1~2 N=CMe2 CH3 H CH3 CF3 H SMe H H Resin
1693 NH2 C2H5 CH3 CH3 H SMe H CH3 H
1694 NH2 C2H5 Ac CH3 H SMe H CH3 H
NH2 C2H5 S02Me CH3 H SMe H CH3 H
'~ t666 NHZ C2H5 c-Pr CH3 H SMe H CH3 H Resin
1697 NHCOCH3 C2H5 H CH3 H SMe H CH3 H
1698 NHCOCH3 C2H5 H CH3 CF3 H SCH3 H H
X699 NHS02CH3 C2H5 H CH3 H SMe H CH3 H Resin
1700 NHS02CH3 C2H5 H CH3 CF3 H SMe H H
1701 N=C(Me)OMeC2H5 H CH3 CF3 H SMe H H Resin
170e N=C(Me)OEtC2H5 H CH3 CF3 H SMe H H Resin
1700 N=C(Me)SMeC2H5 H CH3 CF3 H SMe H H Resin
X704 N=C(CH3)2 C2H5 H CH3 CF3 H SMe H H Resin
'
1706 NH2 i-Pr CH3 CH3 H SMe H CH3 H
CA 02386800 2002-04-05
125
No. A R' R2 R3 R" RS Rs R' Re Phys.
data
1706 NH2 i-Pr Ac CH3 H SMe H CH3 H
1707 NHZ i-Pr SOZMe CH3 H SMe H CH3 H
1708 NHz i-Pr c-Pr CH3 H SMe H CH3 H Resin
17i0ANHCOCH3 i-Pr H CH3 H SMe H CH3 H Resin
1710 NHCOCH3 i-Pr H CH3 CF3 H SMe H H Resin
1711 NHS02CH3 i-Pr H CH3 H SMe H CH3 H Resin
1712 NHSOZCH3 i-Pr H CH3 CF3 H SCH3 H H Resin
r~.
1713 N=C(Me)OMe i-Pr H CH3 CF3 H SCH3 H H Resin
1714 N=C(Me)OEt i-Pr H CH3 CF3 H SCH3 H H Resin
1715 N=C(Me)SMe i-Pr H CH3 CF3 H SCH3 H H Resin
1716 N=C(CH3)2 i-Pr H CH3 CF3 H SCH3 H H Resin
1717 NHZ CHFMe CH3 CH3 H SMe H CH3 H
1718 NH2 CHFMe Ac CH3 H SMe H CH3 H
1719 NH2 CHFMe S02Me CH3 H SMe H CH3 H
1720 NH2 CHFMe c-Pr CH3 H SMe H CH3 H Resin
1721 NHCOCH3 CHFMe H CH3 H SMe H CH3 H
""""' 1722 NHCOCH3 CHFMe H CH3 CF3 H SMe H H
1723 NHS02CH3 CHFMe H CH3 H SMe H CH3 H
1724 NHS02CH3 CHFMe H CH3 CF3 H SMe H H
1725 N=C(Me)OMe CHFMe H CH3 CF3 H SMe H H Resin
17x6 N=C(Me)OEt CHFMe H CH3 CF3 H SMe H H Resin
1727 N=C(Me)SMe CHFMe H CH3 CF3 H SMe H H Resin
1728 N=C(CH3)2 CHFMe H CH3 CF3 H SMe H H Resin
1729 NH2 CHFEt CH3 CH3 H SMe H CH3 H
t730 NH2 CHFEt Ac CH3 H SMe H CH3 H
1731 NH2 CHFEt S02Me CH3 H SMe H CH3 H
CA 02386800 2002-04-05
126
No. A R' R2 R3 R RS R6 R' Re Phys.
data
1732 NH2 CHFEt c-Pr CH3 H SMe H CH3 H Resin
1733 NHCOCH3 CHFEt H CH3 H SMe H CH3 H
1734 NHCOCH3 CHFEt H CH3 CF3 H SCH3 H H
1736 NHS02CH3 CHFEt H CH3 H SCH~H CH3 H
1736 NHS02CH3 CHFEt H CH3 CF3 H SCH3 H H
1737 N=C(Me)OMeCHFEt H CH3 CF3 H SCH3 H H Resin
1738 N=C(Me)OEtCHFEt H CH3 CF3 H SCH3 H H Resin
1739 N=C(Me)SMeCHFEt H CH3 CF3 H SCH3 H H Resin
1740 N=C(CH3)2 CHFEt H CH3 CF3 H SCH3 H H Resin
1741 NH2 CFMe2 CH3 CH3 H SMe H CH3 H
1742 NH2 CFMe2 Ac CH3 H SMe H CH3 H
1743 NH2 CFMe2 SOzMe CH3 H SMe H CH3 H
1744 NHZ CFMeZ c-Pr CH3 H SMe H CH3 H
1745 NHCOCH3 CFMe2 H CH3 H SMe H CH3 H
1746 NHCOCH3 CFMe2 H CH3 CF3 H SCH3 H H
1747 NHS02CH3 CFMe2 H CH3 H SCH~H CH3 H
1748 NHS02CH3 CFMe2 H CH3 CF3 H SCH3 H H
1749 N=C(Me)OMeCFMe2 H CH3 CF3 H SCH3 H H Resin
1750 N=C(Me)OEtCFMe2 H CH3 CF3 H SCH3 H H Resin
1751 N=C(Me)SMeCFMe2 H CH3 CF3 H SCH3 H H Resin
1752 N=C(CH3)2 CFMez H CH3 CF3 H SCH3 H H Resin
1753 NH2 c-Pr CH3 CH3 H SMe H CH3 H
1754 NH2 c-Pr Ac CH3 H SMe H CH3 H
1756 NH2 c-Pr S02Me CH3 H SMe H CH3 H
1756 NH2 c-Pr c-Pr CH3 H SMe H CH3 H Resin
1757 NHCOCH3 c-Pr H I CH3 H SMe H CH3 H Resin
I I ( l I p I I I
CA 02386800 2002-04-05
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No. A R' R2 R3 R4 RS Rs R' Re Phys.
data
1758NHCOCH3 c-Pr H CH3 CF3 H SCH3 H H Resin
1'759NHS02CH3 c-Pr H CH3 H SMe H CH3 H Resin
NHS02CH3 c-Pr H CH3 CF3 H SCH3 H H Resin
1761N=C(Me)OMe c-Pr H CH3 CF3 H SCH3 H H Resin
1762N=C(Me)OEt c-Pr H CH3 CF3 H SCH3 H H Resin
1763N=C(Me)SMe c-Pr H CH3 CF3 H SCH3 H H Resin
1764N=C(CH3)2 c-Pr H CH3 CF3 H SCH3 H H Resin
1766NHZ 1-F-c-PrCH3 CH3 H SMe H CH3 H
1766NH2 1-F-c-PrAc CH3 H SMe H CH3 H
1767NH2 1-F-c-PrS02Me CH3 H SMe H CH3 H
1768NH2 1-F-c-Prc-Pr CH3 H SMe H CH3 H
1769NHCOCH3 1-F-c-PrH CH3 H SMe H CH3 H
1770NHCOCH3 1-F-c-PrH CH3 CF3 H SCH3 H H
1771NHS02CH3 1-F-c-PrH CH3 H SMe H CH3 H
1772NHS02CH3 1-F-c-PrH CH3 CF3 H SCHa H H
1773N=C(Me)OMe 1-F-c-PrH CH3 CF3 H SCH3 H H
1774N=C(Me)OEt 1-F-c-PrH CH3 CF3 H SCH3 H H
1775N=C(Me)SMe 1-F-c-PrH CH3 CF3 H SCH3 H H
1776N=C(CH3)2 1-F-c-PrH CH3 CF3 H SCH3 H H
1777CH3 CCI3 H CH3 H Br F H H Oil
1778CH3 CCI3 H CH3 H CH3 CI H H Oil
1779CH3 CGI3 H CH3 F H F H H Oil
1780Et CCI3 H CH3 H Br F H H
1781Et CCI3 H CH3 H CH3 CI H H
1782Et CCI3 H CH3 F H F H H
1783CH3 CFMe2 H CH3 H Br F H H
CA 02386800 2002-04-05
128
No. A R' RZ R3 R RS R6 R' R8 Phys.
data
1784 CH3 CFMe2 H CH3 H CH3 CI H H
1786 CH3 CFMe2 H CH3 F H F H H
1786 Et CFMe2 H CH3 H Br F H H
1787 Et CFMe2 H CH3 H CH3 CI H H
1788 Et CFMe2 H CH3 F H F H H
1789 CH3 c-Pr H CH3 H Br F H H
1730 CH3 c-Pr H CH3 H CH3 CI H H
1791 CH3 c-Pr H CH3 F H F H H
1792 i-Pr CCI3 H CH3 H Br F H H
1796 i-Pr CCI3 H CH3 H CH3 CI H H
1794 i-Pr CCI3 H CH3 F H F H H
1796 NHCOCH3 CCI3 H CH3 H Br F H H
1796 NHCOCH3 CCI3 H CH3 H Me CI H H
1797 NHCOCH3 CCI3 H CH3 F H F H H
1798 NHS02Me CCI3 H CH3 H Br F H H
1799 NHS02Me CCI3 H CH3 H Me CI H H
'~ 1800 NHS02Me CCI3 H CH3 F H F H H
CA 02386800 2002-04-05
129
B. Formulation examples
a) A dust is obtained by mixing 10 parts by weight of a compound of the
formula (I)
and 90 parts by weight of talc as inert substance and comminuting the mixture
in a hammer mill.
b) A wettable powder which is readily dispersible in water is obtained by
mixing 25
parts by weight of a compound of the formula (I), 64 parts by weight of kaolin-
containing quartz as inert substance, 10 parts by weight of potassium
lignosulfonate and 1 part by weight of sodium oleoylmethyltaurinate as wetter
""'' and dispersant and grinding the mixture in a pinned-disk mill.
c) A dispersion concentrate which is readily dispersible in water is obtained
by
mixing 20 parts by weight of a compound of the formula (I) with 6 parts by
weight of alkylphenol polyglycol ether (~Triton X 207), 3 parts by weight of
isotridecanol polyglycol ether (8 EO) and 71 parts by weight of paraffinic
mineral
oil (boiling range, for example, approx. 255 to above 277°C) and
grinding the
mixture in a ball mill to a fineness of below 5 microns.
d) An emulsifiable concentrate is obtained from 15 parts by weight of a
compound
of the formula (I), 75 parts by weight of cyclohexanone as solvent and 10
parts
,~. by weight of ethoxylated nonylphenol as emulsifier.
e) Water-dispersible granules are obtained by mixing
75 parts by weight of a compound of the formula (I),
10 " of calcium lignosulfonate,
5 " of sodium lauryl sulfate,
3 " of polyvinyl alcohol and
7 " of kaolin,
grinding the mixture in a pinned-disk mill and granulating the powder in a
fluidized bed by spraying on water as granulation liquid.
f) Water-dispersible granules are also obtained by homogenizing and
precomminuting, on a colloid mill,
CA 02386800 2002-04-05
130
25 parts by weight of a compound of the formula (I),
" of sodium 2,2'-dinaphthylmethane-6,6'-disulfonate,
2 " of sodium oleoylmethyltaurinate,
1 part by weight of polyvinyl alcohol,
5 17 parts by weight of calcium carbonate and
50 " of water,
subsequently grinding the mixture in a bead mill and atomizing and drying the
resulting suspension in a spray tower by means of a single-substance nozzle.
C. Biological examples
1. Pre-emergence effect on weeds
Seeds or rhizome pieces of mono and dicotyledonous weed plants are placed in
sandy
lime soil in plastic pots and covered with soil. The compounds according to
the
invention which are formulated in the form of wettable powders or emulsion
concentrates are then applied to the soil cover in the form of aqueous
suspensions or
emulsions at an application rate of 600 to 800 I of waterlha (converted), in
various
dosages.
After the treatment, the pots are placed in a greenhouse and kept under good
growth
,,"" conditions for the weeds. After the test plants had emerged, the damage
to the plants
or the negative effect on the emergence was visually scored after a test
period of 3 to
4 weeks by comparison with untreated controls. As shown by the test results,
the
compounds according to the invention have good herbicidal pre-emergence
activity
against a broad spectrum of weed grasses and broad-leaved weeds. For example,
in
the test the compounds of Example Nos. 4, 6, 12, 13, 15, 16, 17, 18, 46, 48,
49, 51,
67, 68, 69, 71-103, 124, 127, 131, 135-139, 145, 146, 158-174, 209, 215, 216,
218,
219, 220, 221, 242, 249, 251, 252, 254, 270, 272, 274-302, 334, 335, 336, 336,
344,
352, 356-371, 403, 407, 413, 414, 416-419, 440, 447, 449, 450, 452, 468, 470,
472-
500, 524, 532, 542, 543, 544, 547, 551-567, 598, 600, 602-606, 609, 610, 612-
615,
636, 643, 645, 646, 648, 664, 665, 666, 668-696, 714, 717, 718, 738, 742, 746-
762,
793, 795, 830, 839, 840, 842, 859, 860, 862-890, 908, 911, 928, 936, 940-956,
987,
989, 991, 997, 998, 1000-1003, 1024, 1031, 1033, 1034, 1036, 1052-1054, 1056-
CA 02386800 2002-04-05
131
1084, 1102, 1105, 1109, 1116, 1117, 1132, 1136-1152, 1182, 1193, 1194, 1196-
1199,
1220, 1252-1280, 1319-1323, 1326, 1331-1347, 1388, 1389, 1390-1393,1414, 1446-
1474, 1513-1517, 1520, 1524-1540, 1570, 1571, 1573, 1574, 1578, 1580, 1583,
1585-
1590, 1595-1692, 1696, 1699, 1701-1704, 1708-1715, 1720, 1725-1728, 1732, 1737-
1740, 1749-1752, 1756-1764, 1777, 1778 and 1779 (see Tables 1 to 10) have very
good herbicidal activity pre-emergence against harmful plants from the group
consisting of Alopecurus spp., Apera spp., Poa spp., Echinochloa spp., Setaria
spp.,
Digitaria spp., Chenopodium spp., Matricaria spp., Veronica spp., Viola spp.,
Stellaria
spp., Amaranthus spp. or Solanum spp. at an application rate of 0.5 kg or less
of
active substance per hectare.
2. Post-emergence effect on weeds
Seeds or rhizome pieces of mono- and dicotyledonous weeds are placed in sandy
lime
soil in plastic pots, covered with soil and grown in a greenhouse under good
growth
conditions. Three weeks after sowing, the test plants are treated at the three-
leaf
stage. The compounds according to the invention, formulated as wettable
powders or
emulsion concentrates, are sprayed, at various dosages, onto the green parts
of the
plants at an application rate of 600 to 8001 of water/ha (converted). After
the test
plants had remained in the greenhouse for about 3 to 4 weeks under optimum
growth
conditions, the effect of the preparations is scored visually by comparison
with
,,~,, untreated controls. The agents according to the invention also have good
herbicidal
activity post-emergence against a broad spectrum of economically important
weed
grasses and broad-leaved weeds. For example, in the test the compounds of
Example
Nos. 4, 6, 12, 13, 15, 16, 17, 18, 46, 48, 49, 51, 67, 68, 69, 71-103, 124,
127, 131,
135-139, 145, 146, 158-174, 209, 215, 216, 218, 219, 220, 221, 242, 249, 251,
252,
254, 270, 272, 274-302, 334, 335, 336, 336, 344, 352, 356-371, 403, 407, 4013,
414,
416-419, 440, 447, 449, 450, 452, 468, 470, 472-500, 524, 532, 542, 543, 544,
547,
551-567, 598, 600, 602-606, 609, 610, 612-615, 636, 643, 645, 646, 648, 664,
665,
666, 668-696, 714, 717, 718, 738, 742, 746-762, 793, 795, 830, 839, 840, 842,
859,
860, 862-890, 908, 911, 928, 936, 940-956, 987, 989, 991, 997, 998, 1000-1003,
1024, 1031, 1033, 1034, 1036, 1052-1054, 1056-1084, 1102, 1105, 1109, 1116,
1117,
1132, 1136-1152, 1182, 1193, 1194, 1196-1199, 1220, 1252-1280, 1319-1323,
1326,
1331-1347, 1388, 1389, 1390-1393,1414, 1446-1474, 1513-1517, 1520, 1524-1540,
CA 02386800 2002-04-05
132
1570, 1571, 1573, 1574, 1578, 1580, 1583, 1585-1590, 1595-1692, 1696, 1699,
1701-
1704, 1708-1715, 1720, 1725-1728, 1732, 1737-1740, 1749-1752, 1756-1764, 1777,
1778 and 1779 (see Tables 1 to 10) have very good herbicidal activity post-
emergence
against harmful plants from the group consisting of Chenopodium spp., Papaver
spp.,
Polygonum spp., Veronica spp. or Viola spp. at an application rate of 0.5 kg
or less of
active substance per hectare.
3. Action on harmful plants in rice
Transplanted and sown rice and also typical rice weeds (gramineous and broad-
,,.~, leafed) are cultivated in closed plastic pots in a greenhouse to the
three-leaf stage
(Echinochloa crus-galli 1.5-leaf) under paddy rice conditions (height of
water: 2-3 cm).
This is followed by treatment with the novel compounds. For this purpose, the
formulated active compounds are suspended, dissolved or emulsified in water
and
applied by pouring them into the dammed water around the test plants in
different
dosages.
After this treatment, the test plants are set up in the greenhouse under
optimum
growth conditions and are maintained in this way throughout the test period.
About three weeks after application, evaluation is made by visual scoring of
the
damage to the plants by comparison with untreated controls. The compounds
according to the invention show very good herbicidal activity against harmful
plants.
For example, the compounds of Example Nos. 4, 6, 12, 13, 15, 16, 17, 18, 46,
48, 49,
51, 67, 68, 69, 71-103, 124, 127, 131, 135-139, 145, 146, 158-174, 209, 215,
216,
218, 219, 220, 221, 242, 249, 251, 252, 254, 270, 272, 274-302, 334, 335, 336,
336,
344, 352, 356-371, 403, 407, 4013, 414, 416-419, 440, 447, 449, 450, 452, 468,
470,
472-500, 524, 532, 542, 543, 544, 547, 551-567, 598, 600, 602-606, 609, 610,
612-
615, 636, 643, 645, 646, 648, 664, 665, 666, 668-696, 714, 717, 718, 738, 742,
746-
762, 793, 795, 830, 839, 840, 842, 859, 860, 862-890, 908, 911, 928, 936, 940-
956,
987, 989, 991, 997, 998, 1000-1003, 1024, 1031, 1033, 1034, 1036, 1052-1054,
1056-
1084, 1102, 1105, 1109, 1116, 1117, 1132, 1136-1152, 1182, 1193, 1194, 1196-
1199,
1220, 1252-1280, 1319-1323, 1326, 1331-1347, 1388, 1389, 1390-1393,1414, 1446-
1474, 1513-1517, 1520, 1524-1540, 1570, 1571, 1573, 1574, 1578, 1580, 1583,
1585-
1590, 1595-1692, 1696, 1699, 1701-1704, 1708-1715, 1720, 1725-1728, 1732, 1737-
CA 02386800 2002-04-05
133
1740, 1749-1752, 1756-1764, 1777, 1778 and 1779 (see Tables 1 to 10) show very
good herbicidal activity in the test against harmful plants which are typical
for rice
crops, for example Cyperus spp., Echinochloa spp., Digitaria spp., Sagitaria
spp. and
Scirpus spp.
4. Tolerance by crop plants
In further greenhouse experiments, seeds of a substantial number of crop
plants and
weeds are placed in sandy lime soil and covered with soil. Some of the pots
are
treated immediately as described under Section 1, and the remaining pots are
placed
in the greenhouse until the plants have developed two to three true leaves and
then
sprayed with various dosages of the substances of the formula (I) according to
the
invention, as described under Section 2. Visual scoring four to five weeks
after the
application and after the plants have been in the greenhouse reveals that the
compounds according to the invention left dicotyledonous crops such as soya,
cotton,
oilseed rape, sugar beet and potatoes unharmed even when high dosages of
active
ingredient were used by the pre- and post-emergence method. Moreover, some
substances also spare Gramineae crops such as barley, wheat, rye, sorghum, com
or
rice. Some of the compounds of the formula (I) have high selectivity, and they
are
therefore suitable for controlling undesirable vegetation in agricultural
crops.
