A one-step, atom economical synthesis of thieno[2,3- d]pyrimidin-4-amine derivatives via a four-component reaction

Abstract

A Na₂HPO₄-catalyzed four-component reaction between a ketone, malononitrile, S₈ and formamide has been realized for the first time. This reaction provides a concise approach to thieno[2,3-d]pyrimidin-4-amines, previously requiring 5 steps. The utility of this reaction was validated by preparing a multi-targeted kinase inhibitor and an inhibitor of the NRF2 pathway with excellent atom- and step-economy.

Keywords: atom economy; multi-component reaction; structural diversity; thieno[2,3-d]pyrimidin-4-amines.