Development of a Scalable Route to the SMO Receptor Antagonist SEN794

Abstract

A practical and scalable route to the SMO receptor antagonist SEN794 <b>1</b> is described herein. A new and efficient access to the key intermediate <b>7</b> via the Kröhnke reaction was developed, significantly simplifying the synthesis and reducing costs. The optimized route consists of six chemical steps plus a palladium scavenging step. The intermediates are solids and were isolated by filtrations, except for ester <b>9</b>, which was telescoped as the crude oil into the subsequent step. In the final amide formation step, target compound <b>1</b> was conveniently crystallized from the reaction mixture in high purity