Efficient synthesis of uracil-derived hexa- and tetrahydropyrido[2,3-d] pyrimidines

A reaction of 6-amino-1,3-dimethyluracil with 3-(hetero)aroylacrylic acids and their methyl esters leads to hexahydropyrido[2,3-d]pyrimidine-5-carboxylic acids or the corresponding methyl esters in high to excellent yields. One-pot oxidation of the acid derivatives with CAN is accompanied by decarboxylation to give tetrahydropyrido[2,3-d]pyrimidines, while oxidation with bromine resulted in the formation of tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acids. The aromatization of methyl hexahydropyrido[2,3-d]pyrimidine-5-carboxylates was achieved by K₂CO₃-mediated air oxidation under ambient conditions. Pyrido[2,3-d]pyrimidines were synthesized in high to excellent yields by condensation of 3-aroylacrylic acids with 6-aminouracil. Further investigation of the reactivity of the products revealed a new application for K₂CO₃ in the air oxidation of hexahydropyrido[2,3-d] pyrimidines.