SU197948A1 - Method of obtaining water-soluble polymer derivatives of chlorethylamines - Google Patents

Description

The process for the preparation of water-soluble polymeric chloroethylaldan derivatives is known.

In order to obtain x and 1-resistant polymer polyvolume physiologically active compounds, it is proposed to pre-acylated chloroethylamine, for example, N-acyl-n-di (2-chloroethyl) amino-phenylalanine, xd1mich1 and, to combine covalent bonds with copolymer, vinylpyrrolidone and inquiries, and syringes with indentions and indentions. with the subsequent purification of the resulting polymer mixture with an alcoholic solution of HCI.

Polymeric chloroethylamine derivatives are obtained as a result of the interaction of the carboxyl groups of the chloroethylamine derivative and the acyl group of the copolymer to form an amide bond. In the reaction, chloroethylamine is used, the free amino group of which is pre-blocked by acylation of formic or acetic acid. The reaction to form a polyamide is carried out in the presence of water-removing means, for example, N-didiclohexylcarbodiimkda. Specified formyl (PS) or acetyl (AC) derivative of p-da- (2-chloroethyl) amyiophenylalanine

reacting with a copolymer of vinylpyrrolidone and vinylamine with shaking of crystalline PS or AS, taken in an amount close to the equivalent in content of vinylamine units in the copolymer, with a solution of the copolymer in an organic solvent (chloroform, dimethylformamide), to which N-dicyclohexylcarbolcarbol The reaction is carried out at room temperature. A clear solution is formed, from which a crystalline precipitate of dicyclohexylurea then precipitates.

S (DCGM). The polymer products of the reaction remain in solution. They are isolated by precipitation with the addition of zfir. Polymer yield 80% or more from theory. The polymer obtained in powder form is poorly soluble in water.

, HjiH In order to free up the amino group of chloroethylamine by blocking acylating, the polymeric product is hydrolyzed by treating it. at room temperature, alcoholic HCI solution taken in excess. Precipitation of the polymer powder from the reaction solution, which is well soluble in water, is isolated from the reaction solution.

Example. To a suspension of 6 g of formyl or 6.4 g of acetyl derivative of p-di- (2-chloro) -tyl) aminophenylalanine (sarkolizin), obtained by treating the base of sarcoliein with anhydrous acids in the presence of acetic anhydride, the solution is poured into 20 ml of chloro-form 3.72 g of N-dicyclohexylcarbodiimide in 15 ml of chloroform followed by a solution of 22.3 g of a copolymer of vinylpyrrolidone and vinylamine (containing 8.6 mol% of vinylamine in the copolymer chain) with a viscosity fj of 0.19 in 120 ml of chloroform. The mixture is shaken mechanically for 1-2 hours. After 10 minutes from the start of stirring, a clear homogeneous solution is formed, from which a white precipitate of DCGM begins to precipitate. After the completion of the reaction, the mixture is kept in a well, then the DCGM is filtered off. Its output is 3.25 g.

A copolymer of vinylpyrrolidone and N-vinyl amide was removed from the filtrate. p-di- (2-chloroethyl) aminophenylformamyl acetylaminopropionic acid in the form of a light yellow powder with a yield of 21.2 g (82% of theory). The copolymer is then dissolved in 200 ml of 1 and. alcohol solution of HCI at room temperature and stirred for 30 minutes, after which it is precipitated with ethyl or petroleum ether, washed on the filter and dried at 30-40 ° C in vacuum

979484

(5 mm Hg) to crstny weight. Yield 20.1 g (95% of the taken polymer). The powder is a copolymer of vinylpyrrolidone and sarcolysine vinylamide, containing 5.7 mol.% Of the latter in the chain of the copolymer. 5% found: CI 9.6.

Calculated,%: CI 8.9.

Acid number 55. The copolymer is completely soluble in water.

Similarly, the process proceeds with 10 other chloroethylamines of the general form-,.

15 where R is HOOS is CHaCHNdSbN4-, G1soon

MJ-H

Claims (1)

Invention Formula A method for producing water-soluble polymeric derivatives of chloroethylamines, characterized in that, in order to obtain chemically stable polymeric derivatives of physiologically active compounds, previously acylated chloroethyamine, for example, N-acyl-p-di- (2-chlorostil) aminophenylalanine, is reacted with a copolymer of vinylpyrrolidone and v -aluminine copolymer in the presence of dehydrating agents followed by saponification of the resulting polymeric amide with an alcoholic solution of HCI.