Efficient synthesis of 2-aryl-6-chloronicotinamides via PXPd2-catalyzed regioselective Suzuki coupling

A short and convergent synthesis of 2-aryl-6-chloronicotinamides via regioselective Suzuki coupling of 2,6-dichloronicotinamide with aryl boronic acids is described. Regloselectivity was achieved by chelation of the palladium(0) species to an ester/amide group. The air-stable palladium catalyst PXPd2, when used in reagent-grade methanol with K2CO3 as the base, afforded the best regioselectivity and shortest reaction times among the catalysts screened.