v-Triazolo[4,5-d]pyrimidines (8-azapurines). Part X. New routes to v-triazolo[4,5-d]pyrimidines via 4-dimethylaminomethyleneamino-1,2,3-triazole-5-carbonitriles

Abstract

Treatment of various 4-amino-1,2,3-triazole-5-carboxamides with phosphoryl chloride in cold dimethylformamide gave the corresponding 4-dimethylaminomethyleneamino-5-carbonitriles, e.g.(1a). 2-Dimethylaminomethylene-aminobenzonitrile was similarly made from anthranilamide. An improved synthesis of 4-amino-1-methyl-1,2,3-triazole-5-carboxamide is given. By-products from the reactions of this amide and its 2-methyl isomer with phosphoryl chloride and dimethylformamide were the 4-dimethylaminomethyleneamino-N-formyl amides (1b) and (2b), respectively. When melted, these cyclised to 1- and 2-methyl-v-triazolo[4,5-d]pyrimidin-7(6H)-ones (7- and 8-methyl-8-azapurin-6-ones), respectively; when subjected to mild alkaline hydrolysis they yielded 4-dimethylaminomethyleneaminotriazole-5-carboxamides, (1c) and (2c) respectively. The amide (1c) was also prepared from 4-amino-1-methyl-1,2,3-triazole-5-carboxamide, from 4-dimethylaminomethyleneamino-1-methyl-1,2,3-triazole-5-carbonitrile, and from S-methyl 4-amino-1-methyl-1,2,3-triazole-5-thiocarboxylate (5). The NN-dimethylamide corresponding to (1c) was similarly prepared.

With boiling aqueous ammonium acetate, the 4-dimethylaminomethyleneamino-1- and 2-methyl-1,2,3-triazole-5-carbonitriles cyclised to 6-amino-7- and -8-methyl-8-azapurines. The 5-cyano-4-dimethylaminomethylene-amino-3-methyl isomer, a much weaker base, reacted only sluggishly. The 1- and 2-methyl isomers (1a) and (2a) were similarly cyclised by boiling aqueous methylamine acetate, and use of hot ethanolic sodium hydrogen sulphide gave 7- and 8-methyl-8-azapurine-6-thiones [e.g.(6c)]. An improved synthesis of 1-methyl-v-triazolo-[4,5-d]pyrimidin-7(6H)-one (7-methyl-8-azapurin-6-one)(6a) from 4-amino-1-methyl-1,2,3-triazole-5-carbox-amide is given.

Ionisation constants and u.v., i.r., and n.m.r. spectra are discussed.