Purines, pyrimidines, and imidazoles. Part XXXVII. Some new syntheses of pyrazolo[3,4-d]pyrimidines, including allopurinol

Abstract

Pyrazolo[3,4-d]pyrimidines, including the antimetabolites allopurinol and oxyallopurinol and substituted derivatives, have been prepared by reaction of various α-cyano-β-ethoxyacrylamides with hydrazine and substituted hydrazines. α-Cyano-β-ethoxy-N-formylacrylamide was synthesised in a single step from cyanoacetic acid, formamide, triethyl orthoformate, and acetic anhydride. Intermediates in the reactions include amido-N-substituted α-cyano-β-hydrazinoacrylamides and amido-N-substituted 5-aminopyrazole-4-carboxamides, but the ease with which both types of compound cyclise directly to pyrazolopyrimidines has precluded their isolation in all cases. A similar reaction of phenylhydrazine with 5-cyano-2-ethylthio-4-oxo-1,3-thiazine gave, via an acyclic dithiocarbamate and the related 5-amino-1-phenylpyrazole-4-(N-ethylthiothiocarbonyl)-carboxamide, 4-hydroxy-6-mercapto-1-phenylpyrazolo[3,4-d]pyrimidine. Structures have been confirmed by conversion into known compounds, by alternative syntheses, and by spectroscopic studies.