Development of a scalable synthesis of RORγt inverse agonist, BMT-399150

Abstract

The work outlined in this manuscript describes a scalable route to the RORγt inverse agonist BMT-399150 (1), starting from readily available cyclohexane-1,3-dione. The developed process encompasses an efficient synthesis of azatricyclic amine core (13) and the use of Ullman's conditions to install the heptafluoroisopropyl moiety. The synthesis of chiral intermediate (S)-2-hydroxy-2-methyl-3-(methylsulfonyl)propanoic acid (18b) was achieved from readily available benzyl methacrylate. Various synthetic routes were explored to accomplish a scalable protocol to access the title compound 1. This advancement enabled a competent route to the title compound in safe, cost-effective, and scalable manner.