Synthesis of Isomeric Isoxazolopyridinones

Abstract

Reaction of 4-methylamino-5,6-dihydropyridinone with acetyl chloride yielded exclusively the 3-acetyl derivative. When the methylamino group of the latter was removed by alkaline hydrolysis, a mixture of two hydroxy derivatives was formed. Those cyclized upon treatment with hydroxylamine exclusively to the isoxazolo[4,5-c]pyridinone, whereas the 4-methylamino analogue yielded, depending on pH, mainly the isoxazolo[4,3-c]pyridinone or the isoxazolo [4,5-c]pyridinone. The con®gurations of the latter compounds were established by NMR experiments.

Isoxazolodihydropyridinones: 1,3-Dipolar Cycloaddition of Nitrile Oxides onto 2,4-Dioxopiperidines

“…While the reactions of nitrile oxides with cyclic 1,3-diketones and β-ketoesters have been studied, the cycloaddition of nitrile oxides onto heterocyclic 1,3-dicarbonyl compounds has, to our knowledge, not been reported. Although other routes have been reported for the preparation of isoxazolo­[4,5-c]­pyridinones, our method provides convergent access to a variety of diversity points around the core scaffold.…”