CS199199B1 - Method of producing 7-chlor-5-phenyl-3h-1,4-benzodiazepin-2/1h/-one - Google Patents

Description

The present invention relates to a process for the preparation of 7-chloro-5-phenyl-3H-1,4-benzodiazepin-2 (1H) -one of formula I

which is used as a psychopharmaceutical.

A number of methods for the preparation of this compound are known: from 2-haloacetamido-5-chlorobenzophenone by reaction and with ammonia (Swiss Pat. No. 414,652, Austrian Pat. No. 224,124) by the action of 2-amino acids or derivatives thereof 5-chlorobenzophenone (Swiss Pat. No. 414,653), US Pat. No. 3,239,564); from 5-chloro-2-carbobenzoxyglycylaminobenzophenone by the action of halofluoric acids (Swiss Patent Specification No. 414 655); reaction of 2-amino-5-chlorobenzophenone with phthalylglycyl chloride followed by hydrazinolysis of the resulting product (GDR Pat. No. 57,126); reduction of 7-chloro-5-phenyl-3H-1,4-benzodiazepin-2 (1H) -one-4-oxide with phosphorus pentachloride or hydrogen on Raney nickel (Swiss Pat. No. 418,342, Australian Pat. 256 333, French Pat. No. 839 M),

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It has been found that the compound of formula I can be obtained in a preferred manner by the reduction of 7-chloro-5-phenyl-3H-1,4-benzediazepin-2 (1H) -one of formula II

(II) according to the invention, characterized in that the reduction is carried out with iron in an acidic medium at a temperature of 75 to 110 ° C, preferably 85 to 90 ° C, after which the reaction mixture is diluted with an inert organic solvent of an aromatic hydrocarbon type, preferably toluene and then water, cooled to 0-20 ° C and the precipitated product isolated.

Suitably, iron is used as the iron to reduce the compound of formula II.

In carrying out the process according to the invention, it is best to add a solution of the compound of formula H, preferably also in acetic acid, to the preheated slurry of cast iron grits in acetic acid. After completion of the reduction, the reducing agent is filtered off, toluene is added to the filtrate and, after slight cooling, water is gradually added. In doing so, the compound of formula (I) is free of all impurities.

The advantages of the process according to the invention lie primarily in the simple implementation of the reduction and isolation of the product. Without the use of organic solvent extraction, an almost chromatographically pure compound of formula 1 is obtained directly from the reaction mixture in very good yield and does not contain the difficult impurity ohinolone.

*

A further advantage of the process according to the invention is its easy feasibility on a production scale without requiring a complex apparatus. All raw materials are available and commonly used, solvents can be regenerated, the starting material of formula II is an intermediate for the manufacture of another drug.

Further details of the method can be seen from the exemplary embodiment. .

Exemplary embodiment

To a suspension of 19 g of fine cast iron pulp in 50 ml of glacial acetic acid heated to 90 DEG C., while stirring, a slightly warm solution of 41.5 g (0.154 mol) of 7-chloro-5-phenyl-3H-1 is added dropwise over 30 minutes. Of 4-benzediazepin-2 (1H) -one-4-oxide in 160 ml of acetic acid. The temperature is still maintained at 90 ° C and after addition of the solution the reaction mixture is stirred at this temperature for 1 hour.

The hot reaction mixture is filtered, the filter is washed with 250 ml of toluene, which is added to the filtrate. The temperature of the mixture was adjusted to 30 ° C and 800 ml of equally warm water was slowly added with stirring. The mixture was then cooled to below 20 ° C and sucked off after 1/2 hour. The crystalline product is washed on the filter with water and toluene and dried. The toluene is regenerated. Yield 32.1 g, i.e. 82% of theory. Crystallization from butyl acetate or dichloroethane yields a product with m.p.

215-217 ° C.

Claims (2)

A process for the preparation of 7-chloro-5-phenyl-3H-1,4-benzodiazepin-2 (1H) -one of formula I (I) by reducing 7-chloro-5-phenyl-3H-1,4-benzodiazepine-2 / H / -one-4-oxide of formula II (II), characterized in that the reduction is carried out with iron in acetic acid at a temperature from 75 to 110 ° C ^{'8 e} 5-90 g _c * _{e to g P0} removal of a reducing agent, the reaction mixture is diluted with an inert organic solvent of the aromatic hydrocarbon type, preferably toluene and then water, cooled to 0-20 ° C and the precipitated product isolated. 2. A process according to claim 1, characterized in that cast iron pulp is used for the reduction as iron.