Synthesis of 7,8-Dihydropyrido[2,3-d]pyrimidine Derivatives from 4,6-Dichloro-2-(methylsulfanyl)pyrimidine

A new and convenient method for the preparation of 7,8-dihydropyrido[2,3-d]pyrimidine derivatives has been developed utilizing a three-step sequence starting with a commercially available 4,6-dichloro-2-(methylsulfanyl)pyrimidine (DCSMP). Thus, successive treatment of the starting material with LDA and cinnamaldehyde or its derivatives leads to the formation of 3-aryl-1-[4,6-dichloro-2-(methylsulfanyl)pyrimidin-5-yl]prop-2-en-1-ols. After replacement of one of the two chloro-substituents with primary amines, cyclization of the resulting precursors gives the desired products on treatment with methanesulfonyl chloride in the presence of triethylamine.