PROCESS FOR THE PREPARATION OF N-(1-ETHYL-2-PYRROLIDYLMETHYL)-2-METHOXY-5-SULFAMOYL BENZAMIDE

PREPARATION DE BENZAMIDE DE N-(1-ETHYL-2-PYRROLYLMETHYL)-2-METHOXY-5-SULFAMOYLE

English Abstract

ABSTRACT OF THE DISCLOSURE
There is provided a novel method for preparing N-
(1-ethyl-2-pyrrolidylmethyl)-2-methoxy-5-sulphamoyl benzamide,
its acid addition salts with pharmaceutically acceptable inor-
ganic or organic acids and its quaternary ammonium salts,
characterized in that an enamine of the general formula:
<IMG>
wherein R1 represents an organic group, and R2 represents an
acyl group, or salts thereof, is reacted with a 2-methoxy-5-
sulphamoyl benzoic acid or one of its reactive derivative.
The product prepared is an antiemetic.

Claims

The embodiments of the invention in which an exclu-
sive property or privilege is claimed are defined as follows:
1. A method for preparing N-(1-ethyl-2-pyrrolidyl-
methyl)-2-methoxy-5-sulphamoyl benzamide, its acid addition
salts with pharmaceutically acceptable inorganic or organic
acids and its quaternary ammonium salts, characterized in that
an enamine of the general formula:
<IMG>
wherein:
R1 represents an organic group, and R2 represents an
acyl group, or salts thereof, is reacted with a 2-methoxy-5-
sulphamoyl benzoic acid or one of its reactive derivatives.
2. The process of Claim 1, wherein N-(1-ethyl-2-
pyrrolidylmethyl)methyl-3-aminocrotonate is reacted with 2-
methoxy-5-sulphamoyl benzoic acid chloride to form the N-
(1-ethyl-2-pyrrolidylmethyl)-2-methoxy-5-sulphamoyl benzamide.

Description

`- 1078397
The invention relates to a new method of preparing
N-(1-ethyl-2-pyrrolidylmethyl)-2-methoxy-5-sulphamoyl benz-
amide, its salts of addition with pharmaceutically acceptable
inorganic or organic acids, and quaternary ammonium salts.
The benzamide thus prepared has antiemetic properties. `
The method of preparation according to the invention
comprises making enamines of general formula (I) or their
salts react on a 2-methoxy-5-sulphamoyl benzoic acid or one of
its reactive derivatives, e.g. its acid chloride, as follows:
Rl-C=CH-R2 COOH
CH2 ~ , ~C1 + 2 2 ~ reactive derivative
C2H5
;
CO~H-C~ ~
3 2 5
-> H2N02S--~I ,.
In the above formulae:
Rl represents an organic group and
R2 represents an acyl group.
Suitable organic group for the term Rl may include,
for example, an alkyl (e.g., methyl, ethyl, propyl, butyl,
etc.) group and the like.
Suitable acyl group for the term R2 may include, for
example, an alkanoyl (e.g., acetyl, propionyl, etc.) group, an
alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl,
propoxycarbonyl, butoxycarbonyl, etc.) group and the like.

1~78397
The starting compound may be prepared in accordance
with the procedure disclosed in copending Application Ser. No.
254,483 filed June 9, 1976.
The following example is given to illustrate the
invention without imposing any restrictions on it.
EXAMPLE
N~ ethyl-2-pyrrolidylmethyl)-2-methoxy-5-sulphamoyl
-- benzamide
.
5.26 g (0.02 mol) of hydrochloride of N-(l-ethyl-2-
10 pyrrolidylmethyl)methyl-3-aminocrotonate and 200 ml of
dichloroethane were placed in a one litre flask equipped with
an agitator, a thermometer and a condenser.
The mixture was heated until the solids dissolved,
then a hot solution of 5 g (0.02 mol) of chloride of 2- `
methoxy-5-sulphamoyl benzoic acid in 200 ml of dichloroethane
was poured into it in a fine stream. The reaction mixture was ~;
brought to the boil over 6 hours. After about ten minutes
., crystals appeared. The mixture was allowed to cool and left' to stand overnight. The precipitate formed was filtered,
20 dissolved hot in an aqueous solution of hydrochloric acid,
filtered on charcoal and the solution was made alkaline with
ammonia. The crystals formed were filtered, washed with water
and dried in a stove at 50C.
3.7 g of N-(l-ethyl-2-pyrrolidylmethyl)-2-methoxy-5-
sulphamoyl benzamide was obtained (yield 54.2%, M.P. 178C).
.
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.,,.,~ .
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