1,2,3,4,6-Penta-azaindenes (8-azapurines). Part V. A comparison of 1,2,3-triazoles and pyrimidines as intermediates for the preparation of 9-substituted 8-azapurines. Rearrangement of 6-mercapto-8-azapurines and of 4-aminotriazoles

Abstract

The relative usefulness of pyrimidine and 1,2,3-triazole intermediates for making 8-azapurines with or without an alkyl group in the 9-position was evaluated. 4-Amino-, 4-amino-3-benzyl-, and 4-amino-3-methyl-1,2,3-triazole-5-carboxamide, when condensed with formamide, gave 6-hydroxy-, 9-benzyl-6-hydroxy-, and 6-hydroxy-9-methyl-8-azapurine. Of these three reactions, the first was not so useful for preparing 6-substituted 8(9-H)-azapurines as were the corresponding 6-substituted 4,5-diaminopyrimidines. However, 9-benzyl-6-hydroxy-8-azapurine proved a convenient source of the 6-chloro-, amino-, methoxy-, mercapto-, methylthio-, and hydrazino- analogues; the last named was oxidised to 9-benzyl-8-azapurine. Likewise, 6-hydroxy-9-methyl-8-azapurine readily gave the 6-chloro- and mercapto-analogues, but 9-methyl-6-methylthio-8-azapurine (conveniently made from 5-amino-4-methylamino-6-methylthiopyrimidine and nitrous acid) was found to be a good source of 6-amino-(also 6-hydroxy- and hydrazino-)9-methyl-8-azapurine. The 6-hydrazino-analogue was oxidised to 9-methyl-8-azapurine.

An easily reversible rearrangement of 6-mercapto-8-azapurines to 7-amino[1,2,3]thiadiazolo[5,4-d]pyrimidines was discovered.

4-Methylamino-1,2,3-triazole-5-carboxamide was made by debenzylating the 3-benzyl derivative obtained by the action of dimethyl sulphate and alkali on 3-benzyl-4-diformylamino-1,2,3-triazole-5-carboxamide. The equilibrium between 3-methyl-(and 3-benzyl-)4-amino-1,2,3-triazole 5-carboxamide and 4-methyl (and benzyl)amino-1,2,3-triazole-5-carboxamide, was found to favour the former.

Ionisation constants and u.v. spectra are reported and discussed.