Synthesis of a New Class of Pyrido[2,3-d]pyrimidine Derivatives

Significance

An efficient synthesis of pyrido[2,3-d]-pyrimidine-4,7-diones having a seldomly investigated C-6 hydroxyiminoethyl or benzamido substituent pattern is reported. This interesting heterocyclic interconversion is proposed to involve three key steps: Michael addition of the 2,6-diamino-pyrimidinone or naphthalen-2-amine to the 4-aryli­dene-3-methylisoxazolone or the 4-arylidene-2-phenyloxazolone forming a new C-C bond, followed by acid-catalyzed heteroannulation and opening of the oxazolone or isoxazolone ring. Highest yields were observed when a 2:1 volume ratio of DMF and glacial acetic acid was employed, with the latter acting as both solvent and catalyst. Exclusive formation of the trans diastereo­isomers was observed in good yields, with a broad substrate scope.