Development of a Scalable Synthetic Route to BMS-986251, Part 2: Synthesis of the Tricyclic Core and the API

Abstract

BMS-986251, a potent and efficacious RORγt inverse agonist, was synthesized starting from 6-iodotetralone using 13 chemical transformations with only eight isolated intermediates. The synthesis involved a four-step telescoped diastereoselective aza-Michael reaction-annulation sequence followed by installation of the heptafluoro-iso-propyl side chain and final amidation to furnish the desired API.