GB785353A - Substituted pteridine derivatives - Google Patents

Abstract

The invention comprises compounds of the formul <FORM:0785353/IV (a)/1> and <FORM:0785353/IV (a)/2> (wherein R* is an acyl radical or a hydrogen atom, R is an alkoxy or aralkoxy radical, R1 is a hydroxy, alkoxy, aryloxy or aralkoxy radical and R11 is an acyl radical); the preparation of compounds (1) in which R* is an acyl group by reacting a 2-amino-4-R1-6-di-R-methyl-pteridine with an acylating agent, e.g. acetyl, propionyl or butytyl chloride or the corresponding anhydride, benzoyl bromide or benzoic anhydride, advantageously in an inert organic solvent or, preferably, in an excess of the agent under reflux; combination of this reaction with the preparation of compounds (1) in which R* is hydrogen by reacting the corresponding 2-amino - 4 - R1 - 6 - di - R - methyl - 5,6 - dihydropteridine with a mild oxidizing agent, e.g. hydrogen peroxide and a ferrous salt or air, oxygen or iodine, preferably in an alcohol, a glycol, acetone, benzene, formamide, dioxan or water at a pH of about 8 to 9; combination of this reaction with the formation of the dihydropteridine by condensing a 2-halo-3,3-di-R-propionaldehyde with a 2,4,5-triamino-6-R1-pyrimidine, preferably in presence of a condensing agent, e.g. sodium acetate, disodium phosphate, silver carbonate or sodium formate, and a solvent, e.g. water, an alcohol or glycol, acetone, benzene or formamide at 60-65 DEG C.; and the preparation of compounds (2) by hydrolysis with an acid of compounds (1) wherein R* is an acyl group, preferably with a mineral acid or acetic or formic acid in a solvent which may be water, an excess of the acid or an inert organic solvent. In examples: (1) 2-bromo-3,3-diethoxy-propionaldehyde and 2,4,5-triamino-6-benzyloxypyrimidine give 2-amino-4-benzyloxy-6-diethoxymethyl-5,6-dihydropteridine, and this is oxidized to 2 - amino - 4 - benzyloxy - 6 - diethoxymethyl pteridine; (2) 2,4,5-triamino-6-hydroxy pyrimidine (isolated from its sulphate) and 2-bromo-3,3-diethoxy-propionaldehyde (or the 2-chloro compound) give 2-amino-4 - hydroxy - 6 - diethoxymethyl - 5,6 - dihydropteridine which is oxidized to 2-amino-4-hydroxy - 6 - diethoxymethyl pteridine; (3) 2,4,5 - triamino - 6 - hydroxy - pyrimidine hydrochloride and 2-bromo-3,3-dibenzyloxypropionaldehyde give 2 - amino - 4 - hydroxy - 6 - dibenzyloxymethyl - 5,6 - dihydropteridine which is oxidized to 2-amino-4-hydroxy - 6 - dibenzyloxymethyl pteridine; (4) and (5) the final product of (2) is acetylated and propionylated to 2-acetamido- and 2-propionamido-4-hydroxy-6-diethoxymethyl pteridines respectively; (6) the acetamido product of (4) is hydrolysed with formic acid at room temperature to give 2-acetamido-4-hydroxy-6-formyl pteridine. Other compounds of formul (1) and (2) in which the acyl group when present is alkyl-, aryl- or aralkyl-carbonyl also are referred to. Specifications 785,354 and 785,355 also are referred to.