Potential Purine Antagonists. VI. Synthesis of 1-alkyl- and 1-aryl-4-Substituted Pyrazolo[3,4-d]Pyrimidines

Abstract

Various monosubstituted hydrazines have been reacted with ethoxymethylenemalononitrile to yield the corresponding 1-substituted-5-amino-4-cyanopyrazoles (IV). Treatment of IV with concentrated sulfuric acid gave the corresponding 1-substituted-5-aminopyrazole-4-carboxamides (XVI). The structure of 5-amino-1-phenylpyrazole-4-carboxamide was established by an unambiguous synthesis. The preparation of 1-alkyl- and 1-aryl-4-aminopyrazolo [3,4-d] pyrimidines has been accomplished by treating the corresponding 1-alkyl(or aryl)-5-amino-4-cyanopyrazole (IV) with boiling formamide. Heating l-alkyl(or aryl)-5-amino-4- pyrazolecarboxamide (XVI) with formamide in a similar manner gave the corresponding 1-alkyl(or aryl)-4-hydroxypyrazolo- [3,4-d]pyrimidine (XVII). Phosphorus oxychloride and XVII yielded the 1-alkyl- or 1-aryl-4-chloropyrazolo[3,4-d]pyrimidine (XVIII) which then was utilized for the synthesis of various additional 4-substituted pyrazolo[3,4-d]pyrimidines by nucleophilic displacement of the chlorine atom. © 1956, American Chemical Society. All rights reserved.