GB937724A - New pyrazolo-pyrimidines and process for the preparation thereof - Google Patents

Abstract

The invention comprises a pyrazolo [3,4-d] pyrimidine of the formula <FORM:0937724/IV(a)/1> or a tautomer thereof, in which R1 represents a hydrogen atom or an alkyl, hydroxyalkyl, oxaalkyl, cycloalkyl, cycloalkylalkyl or aralkyl group or at most binuclear aryl or heterocyclic group, R3 represents a hydrogen atom or a lower alkyl group, and R6 represents an aralkyl group, salts thereof, pharmaceutical compositions thereof, and a process for the manufacture of compounds of the above formula wherein a 2-R1-3-amino-5-R3-pyrazole-4-carboxylic acid ester is reacted with a carboxylic acid of the formula R6-COOH in the form of its amide or nitrile or a 2-R1-3-amino-5-R3-pyrazole-4-carboxylic acid amide is reacted with a carboxylic acid of the formula R6-COOH in the form of its anhydride, or amide, or with a corresponding halide or nitrile. When R6 represents aralkyl, the phenyl nucleus may be mono-, di-, or tri-substituted by chlorine, methoxy, methylenedioxy, methyl, trifluoromethyl, amino or nitro groups. In a similar manner R1 may represent substituted phenyl. In a modification of the above process 2-R1-3-amino- 5-R3- pyrazole- 4-carboxylic acid amide is replaced by the nitrile, reacted with the derivative of the acid R6,COOH, converted into the amide followed by ring closure. Intermediate compounds having the formula: <FORM:0937724/IV(a)/2> are obtained by eliminating water from 2-R1-3-(R6-CONH)-4-carboxy-pyrazoles, e.g. with acetic anhydride. These compounds may be reacted with ammonia to obtain the acid amide. 2-(b -Hydroxyethyl)- 3-amino-4-carbethoxypyrazole is obtained by heating ethoxymethylene cyanoacetic ester with b -hydroxyethyl hydrazine. 2-[11-Ethoxy-butyl-(31)] -3-amino-4-carbethoxy pyrazole is obtained by heating ethoxymethylene cyanoacetic ester with 1-ethoxy-butyl-(3)-hydrazine. 2-a -Pyridyl-3-amino- 4-carbethoxy-pyrazole is obtained by heating ethoxy-methylene-cyanoacetic ester with 2-hydrazino-pyridine. 2-Isopropyl-3-[a -ethoxyb -(p-chlorophenyl) -ethylidene-amino]-pyrazole-4-carboxylic acid amide is obtained by forming the imino ether hydrochloride from p-chlorobenzyl cyanide and dry HC1 and boiling this with 2-isopropyl-3-amino-4-carbonamido pyrazole. 2-Isopropyl-3-(p-chloro-phenyl-acetylamino)-4-pyrazole-carboxylic acid nitrile is obtained by reacting 2-isopropyl-3-amino-4-cyano-pyrazole with p-chloro-phenylacetic acid chloride. 2-Isopropyl-3- (p-chlorophenyl-acetylamino)-4-carboxy-pyrazole is obtained by reacting p-chlorophenylacetic acid chloride with 2-isopropyl-3-amino-4-carboxy pyrazole. 1-Isopropyl-4-oxo- 6-(p-chlorobenzyl)-pyrazolo-[3,4-d] oxazine is obtained by heating 2-isopropyl-3-(parachlorophenyl-acetylamino)-4-carboxy-pyrazole with acetic anhydride. p Said compositions containing compounds of the first mentioned formula and having coronary-dilating action are administered as tablets or dragees or in liquid form as solutions, suspensions or emulsions. Specifications 937,725 and 937,726 are referred to.