MC1008A1 - New process for the preparation of N- (diethylaminoethyl) -2-methoxy-4-amino-5-chlorobenzamide - Google Patents

Description

1

£1008

PATENT FOR INVENTION

Filed by the public limited company known as:

SOCIETY FOR SCIENTIFIC AND INDUSTRIAL STUDIES

FROM ILE-DE-FRANCE

Subject:

NEW PROCESS FOR PREPARING N(DIETHYLAMINOETHYL) 2-METHOXY 4-AMTNO 5-CHLOROBENZAMIDE

of the preparation of N(diethylaminoethyl) 2-methoxy 4-amino 5-κhlorobenzamide (III), of its addition salts with pharmaceutically acceptable mineral or organic acids, of quaternary ammonium salts obtained by reacting this benzamide (III) with an alkylating agent.

Priority of the French application: no. 72/22695, filed on June 22, 1972

The present invention relates to a new method

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2

10

The benzamide of the present invention is obtained by treating a halide of 2-methoxy 4-acetamino 5-chlorobenzoic acid (i) with 2-chloroethylamine to obtain N(2-chloroethyl) 2-methoxy 4-acetamino 5-chlorobenzamide (ii). This compound, when treated with diethylamine, yields the desired N(diethylaminoethyl) 2-methoxy 4-amino 5-chlorobenzamide (III).

This benzamide has interesting pharmacological properties as an antiemetic and digestive behavior modifier.

The reaction scheme is as follows:

COX

15

20

25

OCH-

h2nch2ch2ci

NHCOCH-(I)

Ç0NHCH2CH2C1

diethylamine

NHCOCH-(II)

Ç0NHCH2CH2C1

OC H.

3

NHCOCH-

(II)

C0NHCHoCH„N

d. d. -

CgHp.

C2H5

The following example illustrates, without limiting it, the present invention.

N(diethylaminoethyl) 2-methoxy 4-acetamino 5-chlorobenzamide STAGE I: N(2-chloroethyl) 2-methoxy ^--acetamino 5-chlorobenzamide 1) In a 500 ml beaker, 70 g (0.6 mol) of 2-chloroethylamine hydrochloride is dissolved in 100 ml of water, alkalized using 200 ml of 20% sodium hydroxide, maintaining a temperature below 20°C and the solution is immediately extracted three times with 150 ml of benzene.

The organic solution is dried over magnesium sulfate, filtered and adjusted to 500 ml in a volumetric flask.

An alkalinity assay led to a concentration of 5*56 g of amine per 100 ml of solution.

2) In a 500 ml flask equipped with a stirrer and a thermometer, 100 ml of the previous solution, 25 ml of triethylamine, 260 ml of methylethyl ketone are introduced, cooled between 5 and 10°C and 18^5 S of 2-methoxy 4-amino 5-chlorobenzoyl chloride are added in portions.

The mixture is then left to agitate for thirty minutes at 5-10°C, followed by six hours with the cooling bath removed. It is left to stand overnight, and the precipitate is filtered. After washing with water, this precipitate yields 2.7 g of insoluble material.

The filtrate is evaporated to dryness and the residue is taken up with JO ml of ether, filtered, washed twice with 10 ml of ether, and dried in an oven at 50°C.

We obtain 14.2 g of N(2~chloroethyl) 2-methoxy 4-acetaraino 5-chlorobenzamide (F : 160°C).

STAGE II î N(dlethylaminoethyl) 2-methoxy 4-amino 5-chlorobenzamide

In an autoclave, 3.5 S (0.01 mol) of N(2-chloroethyl) 2-methoxy 4-acetamino 5-chlorobenzamide and 35 mL of diethylamine are introduced. The mixture is heated for eight hours at 70°C. The suspension is then evaporated under vacuum, 100 mL of water is added to the residue, the mixture is acidified to pH 1 with hydrochloric acid, filtered, the filtrate is alkalinized with sodium hydroxide, and the mixture is refluxed for thirty minutes.

It is cooled, filtered, washed with water, and dried in an oven.

at 50°C.

We obtain 1.7 g of N(diethylaminoethyl) 2-methoxy 4-amino 5-chlorobenzamide (F : 143°C).

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Claims (10)

DEMANDS 1) New process for the preparation of N(diethylaminoethyl) 2-methoxy 4-amino 5-chlorobenzamide corresponding to the formula ✓CjjHL C0NHCHoCHoN * 2 2 x02H5 10 of its addition salts with pharmaceutically acceptable mineral or organic acids, of its quaternary ammonium salts, characterized in that a halide of 2-methoxy 4-acetamino 5-chlorobenzoic acid is reacted with 2-chloroethyl 15-amino to obtain N(2-chloroethyl) 2-methoxy 4-acetaminophen 5-chlorobenzamide, the latter compound being treated with diethylamine to obtain N(diethylarninoethyl) 2-methoxy 4-amino 5-chlorobenzamide desired. 2) Process according to 1) in which the acid halide used is 20 2-methoxy 4-acetamino 5-chlorobensoyl chloride. ■ ffcofyoW sokos , ceov/tfi nor me noV. oi (y\0\ cv\o^rg 'SOCIETY FOR SCIENTIFIC AND^ STUDIES '• INDUSTRIELLES DE Lille-DE-FRANCE' THE AGENT 0 J. EPU - AN