Synthesis of 2-Cyanopyrimidines

Abstract

4,6-Dichloro-2-(methylthio)pyrimidine (7) was converted to 4-chloro-6-methoxy-2-(methylthio)pyrimidine (15) and 4,6-dimethoxy-2-(methylthio)pyrimidine (14). Chlorination of the latter with N-chlorosuccinimide (NCS) affords 5-chloro-4,6-dimethoxy-2-(methylthio)pyrimidine (16) in 56% yield. Both methylthiopyrimidines 15 and 14 were converted in two steps to 4-chloro-6-methoxypyrimidine-2-carbonitrile (13) and 4,6-dimethoxypyrimidine-2-carbonitrile (12), respectively, after oxidation to sulfones and displacement of the sulfinate group with KCN. 4,6-Dimethoxypyrimidine-2-carbonitrile (12) was chlorinated with NCS to give 5-chloro-4,6-dimethoxypyrimidine-2-carbonitrile (10) in 53% yield. All new compounds were fully characterized.