Highly selective substitutions in 2,3-dichloropyrazine. A novel general approach to aloisines

Abstract

A highly efficient synthesis of the potent CDKs (cyclin-dependent kinases) inhibitors, aloisines (substituted 5 H-pyrrolo[2,3- b]pyrazines) is presented. The method is based on highly selective monosubstitution of a single chlorine atom in 2,3-dichloropyrazine with lithiated ketones, esters, and nitriles followed by co-cyclization of the resulting intermediates with primary amines or hydrazines.