A New Synthesis of 4,5,6,7-Tetrahydropyrazolo[1,5-c]pyrimidines by a Retro-Mannich Cascade Rearrangement

Abstract

We discovered a new retro-Mannich reaction of in situ prepared pyrazolopyridines to give pyrazolopyrimidines that have hitherto been underrepresented in the heterocyclic chemistry literature. The isolation of a linear hydrolysis product supports a mechanistic hypothesis for this rearrangement process. In order to establish a broader access and explore potential biological applications for these medicinal chemistry building blocks, we investigated the scope of the reaction and generated small amine- as well as amide-based libraries through reductive aminations and amide couplings, respectively.