A Short, Efficient Synthesis of the Novel Cholinergic Channel Activator, ABT 418, from L-Proline

Abstract

A short and efficient synthesis of the novel cholinergic channel activator ABT 418, (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole, has been developed. The four-step route from L-proline afforded the target compound in ca. 35% overall yield in very high chemical and enantiomeric purity. This route has afforded multigram quantities of the clinical candidate and should be amenable to kilogram-scale reactions.