Convenient synthesis of 2,4-disubstituted pyrido[2,3-d]pyrimidines via regioselective palladium-catalyzed reactions

A novel and effective route for the synthesis of 2,4-disubstituted pyrido[2,3-d]pyrimidines III is reported starting from the corresponding 2,4-dichloropyridopyrimidine 1 through regioselective functionalization palladium-catalyzed C–C coupling reactions, by two successive palladium-catalyzed reactions involving an original regioselective chlorine discrimination. Alternatively, type III compounds were elaborated from 2 by C-2 chlorine further displacement of the C-4 isopropylsulfanyl group, which acted as a temporary C-4 protecting group. Further Suzuki–Miyaura cross-coupling reactions led to C-2 and C-4 disubstituted compounds.