Application of C–H Functionalization in the Development of a Concise and Convergent Route to the Phosphatidylinositol-3-kinase Delta Inhibitor Nemiralisib

Abstract

This paper describes the development of an improved and scalable method for the manufacture of nemiralisib, a phosphatidylinositol-3-kinase delta inhibitor. Incorporation of three consecutive catalytic reactions, including a palladium-catalyzed C–H functionalization and an iridium-catalyzed borylation, significantly simplified and shortened the synthetic sequence. The revised route was successfully implemented in a pilot plant on a multikilogram scale to deliver >100 kg of product.