Reconstructive Approach to the Regiospecific Synthesis of N9‐Alkylated Purines

Abstract

AbstractA regiospecific synthesis of N9‐alkylated purines as novel acyclic nucleosides was developed. This approach is based on reconstructive methodology involving the construction of a target heterocyclic scaffold on a readily available 5‐aminotetrazole moiety, which is subsequently cleaved under reductive conditions due to azido‐tetrazole tautomerism. It appeared that the rate of reduction for the azide fragment in 6‐nitro‐7‐alkylaminotetrazolo[1,5‐a]pyrimidines is much greater than the rate of nitro group reduction. Treatment of these heterocycles with hydrogen over a palladium catalyst resulted in the formation of triaminopyrimidines in excellent yields through the reduction of both the azide and nitro group. Triaminopyrimidines were transformed into the desired N9‐alkylated purines, and an analog of the marketed drug penciclovir was synthesized by the developed method.