TERTIARY-ALKYLAMINO-LOWER ACYL-XYLIDIDES

ALKYLAMINO-ACYL (A CHAINE COURTE)-XYLIDIDES TERTIAIRES

English Abstract

ABSTRACT OF THE DISCLOSURE

The invention is the compound 2-(N-tert.amylamino)-2',6'-
acetoxylidide and its acid addition salts. The compound is a useful inter-
mediate in the production of 2-(N-ethyl-tert. amylamino)-2',6'-acetoxylidine
and 2-(N-n-propyl tert.amylamino)-2',6'-acetoxylidide, which are useful
local anaesthetics having long lasting effects.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for preparing the compound 2-(N-tert.amylamino)-2',
6'-acetoxylidide of formula

Image

which comprises reacting a compound of formula

Image

in which X is chlorine, bromine or iodine, with tert.-amylamine, and if de-
sired converting the product into an acid addition salt.

2. A process according to claim 1 wherein X is chlorine or bromine
the reaction is carried out in the presence of an alkali metal iodide or a
quaternary ammonium iodide.
3. A process according to claim 2 wherein 2-chloro-2',6'-acetoxyl-
idide is reacted with tert.-amylamine in the presence of sodium iodide.

4. A process according to claim 3 wherein the product of the reaction
between 2-chloro-2',6'-acetoxylidide and tert.amylamine is reacted with
hydrogen chloride to obtain the hydrochloride salt.
5. The compound 2-(N-tert.-amylamino)-2',6'-acetoxylidide when made
by a process according to claim 1 or by an obvious chemical equivalent thereof.
6. The compound 2-(N-tert.-amylamino)-2',6'-acetoxylidide hydro-
chloride when made by a process according to claim 4 or by an obvious chemi-
cal equivalent thereof.

Description

This application is a divisiona] of our copending Canadian
patent application Serial No. 164,740, filed February 27~ 1973.
This application Telates to the compound 2-~N-tert.amylamino)-
2',6'-acetoxylidide.
Our copending Canadian patent application Serial No. 164,740
relates to 2-(N-ethyl-tert.amylamino)-2',6'-acetoxylidide and 2-~N-n-propyl-
tert.-amylamino)-2',6'-acetoxylidide, their pharmaceutically acceptable salts
and their use as local anaesthetics. -
This invention relates to a novel compound which is a useful
intermediate in the production of the compounds which are the subject of our
application Serial No. 164,740. The novel compound is 2-~N-tert.-amylamino)-
2',6'-acetoxylidide, of the formula
.
CH,



\ 1 3
CH3 1 2 3


The invention also relates to the acid addition salts of the
compound.
The compound 2-(N-tert. amylamino)-2',6'-acetoxylidide can be
prepared by reacting a compound of formula




~ NH-C-CH~-X
CH3




in which X is chlorine, bromine or iodine, with tert. amylamine.
~hen X is chlorine or bromine the reaction is preferably
carried out in the presence of an alkali metal iodide, for example, sodium
iodide or potassium iodide or a quaternary ammonium iodide.
The compound 2-(N-ter~.-amylamino)-2',6'-acetoxylidide can be
reacted with an alkylating agent to ob~ain 2-(N-ethyl.tert~ amylamino)-2',6'-
acetoxylidide of 2-~N~n-propyl-tert.amylamino)-2'~6'-acetoxylidide in accor-




-- 2 --

dance with our copending application Serial No. 164~740.
The invention is ~urther illustrated in the following Example
showing the preparation of 2-(N-tert.amylamino)-21~6~-aeetoxylidide.
To 400 ml of anhydrous benzene, 18.9 g (0.09S6 mole) 2-chloro-
2l~6t-acetoxylidide~ 20 g (0.2295 mole) tert.amylamine and 1 g. of sodium
iodide were added. The reaction mixture was heated at 100C for 36 hours
in an autoclave. A precipitate was collected and discardedO The resulting
filtrate was stripped of solvent and the yellow oily residue was dissolved
in ether, the undissolved material being collected and discarded~ After
drying (Na2S04) the ether was stripped off in vacuo leaving a yellow oily
liquid which was taken up in dilute hydrochloric acid (~inal pH 2)c The
acidic aqueous phase was washed several times with ether, basified to pH
9.5 with concentrated ammonia, and the preeipitated base extracted with
ether (4xlO0 ml3. The ether extract was dried (Na2S04) and evaporated
n vacuo leaving a yellow oily residue which was distilled in vacuo (b.p.
150C., 0.02 mm.) to give under refrigeration, 16.6 g. of a white solid~
m~p. 54-55.5C~ (The hydrochloride was also prepared and recrystallized
from acetonitrile, m.p. 209-211C.)
Anal. Caled. for C15H24N20: C~ 72-54; H~ 9-74; N~ 28-
Found: C, 72032; H, 9.98; N~ 11.34c I.r, (~Br disc~ hydrochloride) 3150-3120
(m-s; amide, NH streteh); 2710 (s), 2620 (m)~ 2580 (m~ 2440 (m~ and 2417
(m-w) (NH+ streteh)/ .1665 (s; amide I). 1590 (m-w; aromatic~ 1542 (S3 amide
II), 1393 and 1375 (s-m; methyl CH bending), 775 (s~m; 3 adjacent out of
plane aromatic H) cm 1.




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