A Four-Component Reaction Strategy for Pyrimidine Carboxamide Synthesis

Abstract

Demonstrated herein is a highly effective 3 starting materials-4 component reaction (3SM-4CR) strategy for the synthesis of pyrimidine carboxamides from amidines, styrene, and N,N-dimethylformamide (DMF) by a palladium-catalyzed oxidative process. This transformation represents the first example of employing DMF as a dual synthon, a one-carbon-atom synthon and amide synthon, and was proven by isotope-labeling experiments. Additionally, the combination of C-H bond functionalization and cross-dehydrogenative coupling processes affords four chemical bond formations. This sequential 3SM-4CR strategy features inexpensive, readily available starting materials, green oxidants, as well as atom and step economy. It leads to the preparation of pyrimidine carboxamides and has potential applications in the pharmaceutical industry.

Keywords: cyclization; heterocycles; multicomponent reactions; palladium; synthons.