Process Development of a GCS Inhibitor Including Demonstration of Lossen Rearrangement on Kilogram Scale

Abstract

A small molecule was under investigation as an inhibitor of glucosylceramide synthase (GCS) for potential use in Fabry disease. To support preclinical activities, a four-step synthesis was developed and used to prepared kilogram quantities of the drug substance. The new route features a scalable CDI-mediated Lossen rearrangement as a substitution for hazardous azide chemistry that was employed in the original route.