Manufacturing Process Development for Belzutifan, Part 1: A Concise Synthesis of the Indanone Starting Material

Abstract

A four-step synthesis of the indanone core of belzutifan (MK-6482) is described. This route starts from the commodity raw material dihydrocoumarin and was successfully demonstrated on a large scale to produce indanone 11 in the synthesis of belzutifan, an FDA-approved first-in-class therapy for the treatment of patients with certain types of Von Hippel–Lindau disease-associated tumors.