Patent GB-954094-A (GB)
Title: Improvements in or relating to alkylidene derivatives of 6-pteridinehydrazides and amidrazones
IPC: C07D475/10
Filed: 1961-11-22
Abstract: The invention comprises pteridines of the general formula: <FORM:0954094/C2/1> wherein Ar represents a thienyl or pyridyl radical or a radical of the formula: <FORM:0954094/C2/2> R represents O or NH; R1 represents hydrogen or an alkyl radical containing not more than 4 carbon atoms, a furyl radical or a radical of one of the formulae: <FORM:0954094/C2/3> R2 represents an alkyl radical as defined above, a furyl radical or a radical of either formula immediately above; R3, R4 and R5 represent hydrogen or an alkyl radical as defined above; and R6 represents hydrogen, chlorine, bromine or fluorine or a methyl, methoxy, trifluoromethyl, hydroxy or amino group and pharmaceutically acceptable and addition salts thereof such as the hydrochloride, sulphate, methyl-sulphonate and phosphate salts; and the preparation thereof by reacting pteridines of the general formula: <FORM:0954094/C2/4> wherein Ar, R, R3, R4 and R5 have the abov significance, with a carbonyl compound of the formula: <FORM:0954094/C2/5> wherein R1 and R2 have the above significance.  4, 7-Diamino -2- (m-bromophenyl) -6- pteridine-carboxylic acid hydrazide is prepared by reacting m-bromobenzamidine with the silver salt of isonitroso-malononitrile to form 4, 6-diamino-3-(m-bromo-phenyl)-5-isonitrosopyrimidine, reacting this compound with methyl cyanoacetate and sodium methoxide to form methyl 4, 7-diamino-2-(m -bromaphenyl) - 6 - pteridinecarboxylate, and reactoring this compound with hydrazine. 4, 7-Diamino-2- (p-chlorophenyl) -6- pteridine-amidrazone is prepared by heating p-chlorobenzamidine hydrochloride and the silver salt of isonitrosomalononitrile to form 4, 6-diamino-2-(p-chlorophenyl)-5-nitrosopyrimidine, heating this compound with malononitrile and pyridine to form 2-(p-chlorophenyl)-4, 7-diamino-6-cyanopteridine, and reacting this compound with hydrazine.  4, 7-Diamino-2-(4-pyridyl)-6-pteridine-amidrazone is prepared by a similar method using isonicotinamidine hydrochloride in place of the p-chlorobenzamidine as the initial reactant.  4, 7-Diamino-2-(p-tolyl)-6-pteridine-isopropyla-midrazone is prepared by reacting p-toluamidine hydrochloride and isonitrosomalonomtrile to form 4, 6-diamino-5-nitroso-2-(p-tolyl)-pyrimidine, heating this compound with malononitrile and pyridine to form 2-(p-tolyl)-4, 7-diamino-6-cyanopteridine, and heating this compound with isopropylhydrazine.  4, 7-Diamino -2- (o-butoxyphenyl) -6- pteridine-amidrazone is prepared by reacting o-butoxybenzamidine hydrochloride and the sliver salt of isonitrosomalononitrile to form 4, 6-diamino-2-(o-butoxy-phenyl)-5-nitrosopyrimidine, heating this compound with malononitrile and pyridine to form 2-(o-butoxyphenyl)-4, 7-diamino-6-cyanopetridine, and reacting this compound with hydrazine.  This series of reactions may also be carried out using m-bromobenzamidine as the initial reactant. 7-Amino -4- methylamino -2- phenyl-6-pteridine-amidrazone is prepared by heating 6-amino-4-methylanino-5-nitroso-2-phenylpyrimidine with malononitrile and pyridine to form 2-phenyl-7-amino-4-methylamino-6-cyanopteridine and reacting this compound with hydrazine.