DE2409390A1 - PROCESS FOR THE PREPARATION OF N (DIAETHYLAMINOAETHYL) -2-METHOXY-4-AMINO-5CHLOROBENZAMIDE - Google Patents

Description

regards! Jpociete d'Etudes Scientifiques et Industrielles i | jj.e 1'Ile-de-France, S.A., Paris 7, France.

"Process for the preparation of N- (diethylaminoethyl) -2-methoxy 4-a% ino-5-chlorine "benzamide"

The sensing relates to a new process for making N- (Difä.thylaminoäthyl) -2-meth.oxy-4-amino-5'-chlorobenzamide of the formula IJI

CONHCH ₂ CH ₂ N

(III)

and its pharmacologically acceptable acid addition salts with aiiorganisehen or organic _acids} and its quaternary ammonium salts formed by reacting the benzamides of the formula III with e | nem alkylating agent are obtained.

409835/1059

-2-2A09390

The ^ experience of the invention is characterized in that one Z-Meijhoxy- ^ acetamino-S-chlorobenzoyl chloride of the formula I. with Lead1; hiocyanate with formation of 2-methoxy-4-acet-

aminq-5-chlorobenzoyl isothiocyanate of the formula II converts, and this then with ϊϊ, ΪΓ-diethylaminoethylenediamine with formation of N- (diethylaminoethyl) -2-methoxy-4-amino-5-chlorl3enzamide of formula III implements.

The reaction proceeds according to the following scheme:

COCl

OCH,

1/2 Fb (SCN)

2

NHCOCH-

CO-N-C-S

OCH,

NHCOCH. (II) ''

C ₂ H ₅ Ό.

CO - N - C - S

OCH,

NHCOCH (II)

CONHCH ₂ CH ₂ N

The example explains the invention without signifying a restriction.

409835/1069

example N- (diethylaminoethyl) -2-me1; ho3Cy-4-amino-5-chloro) enzamide

Level 1 ; 2-methoxy-4-acetamino-5-ehlorb enz oyli s ο thi ο cyanate

A 500 ml capacity, equipped with a stirrer, thermometer and condenser Flask is filled with 8 g (0.025 mol) of lead thioeyanate and 100 ml Charged with benzene.

Heat to the boil, do a solution to obtain, then cool to flt about 50 ° C and then added in portions with 2-Me ^ Jhoxy-4-acetamino - 5-chlorobenzoyl chloride.

After heating under reflux for 5 hours, the lead chloride formed is filtered off in the heat, the piltrate is cooled and the precipitate formed is filtered off. After washing with a little cold benzene and drying in a desiccator under reduced pressure, 7.3 g (52 percent yield) of 2-methoxy-4-acet ^ mino-S-chlorobenzoyl isothiocyanate from 3P are obtained. 144 ⁰ C

Stage 2: N- (diethylaminoethyl) -2-methoxy-4-amino-5-chlorobenzamide

In a 250 ml, with stirrer, thermometer and a bromine ampoule

provided flask are 2.3 g (0.02 mol) of Ν, Ν-diethylaminoäthylendiaain and 10 ml of methyl ethyl ketone, while maintaining the temperature at about 20 ° C., dropwise with a solution of 2-methoxy-4-acetamino-5-chlorobenzoyl isothiocyanate in 60 ml of methyl ethyl ketone}, offset.

The reaction mixture is then left to react for 5 hours, then the solvent is dried under reduced pressure evaporated, the residue is taken up in 40 ml of water and the reaction product is precipitated with caustic soda or soda.

409835/1059

Naoji, is obtained crystallizing in the refrigerator overnight, filtration, Vaschen with water and drying in a drying oven "at 5O ⁰ C 2.35 g (40 percent yield) of N- (diethylaminoethyl) -2-methoxy-4-amino-5- chlorobenzamide dated Έ. 142 ⁰ C.

Pat spoke

409835/1059

Claims (1)

Claim Process for the preparation of N- (diethylaminoethyl) -2-methoxy-4-amineq> -5-chlorobenzamide of formula III CONHCH ₂ CH ₂ N ^N C _O H _K (III) sowiq> its pharmacologically acceptable acid addition salts with inorganic or organic acids and their quaternary ammonium salts, characterized in that that nian 2-methoxy-4-acetamino-5-chlorobenzoyl chloride with lead thioqjyanat with formation of the 2-methoxy-4-acetamino-5-chlorobenzoyl isocyanate converts, and this then with Ν, Ν-diethylamine-ethylenediamine with formation of N- (diethylaminoethyl) -2-methQxy-4-amino-5-chlorobenzamide of the formula III and optionally converting the free bases into the salts. 409835/1059