Synthetic Protocol for Pyrido[2,3-c]pyridazine and Pyrido[3,2-e][1,2]oxazine Scaffolds via a [4 + 2] Cycloaddition Reaction.

Abstract

Here, we revealed a convenient synthetic protocol for unique pyrido[2,3-c]pyridazine and pyrido[3,2-e][1,2]oxazine scaffolds with excellent regioselectvity and diastereoselectivity. The functionalized pyrido[2,3-c] pyridazines were successfully synthesized via a Cs₂CO₃-promoted [4 + 2] cycloaddition reaction of α-halogenated N-tosylhydrazones or N-acylhydrazones and 5,6-unsubstituted 1,4-dihydropyridines under mild conditions. Additionally, the similar base-promoted [4 + 2] cycloaddition reaction of α-chlorogenated oximes and 5,6-unsubstituted 1,4-dihydropyridines afforded functionalized pyrido[3,2-e][1,2]oxazines in satisfactory yields. The features of this reaction included mild reaction conditions, broad substrate scopes, high functional group tolerance, and significant atomic economy.