Download PDF
Synfacts 2021; 17(11): 1177
DOI: 10.1055/s-0040-1720909
Synthesis of Natural Products and Potential Drugs

Synthesis of the Tricyclic Core of BMS-986251

Contributor(s):
Philip Kocienski
Kalidindi S, Gangu AS, Kuppusamy S, Sathasivam S, Shekarappa V, Murugan S, Bondigela S, Kandasamy M, Ghanta K, Vinodini A, Shrikant A, Ramachandran R, Gallagher WP, Kopp N, González-Bobes F, *, Eastgate MD, Vaidyanathan R. * Bristol-Myers Squibb, New Brunswick, USA and Bristol-Myers Squibb Research and Development Center, Bangalore, India
Development of a Scalable Synthetic Route to BMS-986251, Part 2: Synthesis of the Tricyclic Core and the API.

Org. Process Res. Dev. 2021;
25: 1556-1572
DOI: 10.1021/acs.oprd.1c00125
CrossrefSearch in Google Scholar
› Further Information
 
 PDF Download Permissions and Reprints

Key words

BMS-986251 - halogen–metal exchange - deoxyfluorination - annulation

Significance

RORγt is a nuclear receptor that regulates the production of proinflammatory cytokines, such as IL-17 and IL-22. BMS-986251 is a RORγt inverse agonist that is of interest for the treatment of immunological disorders. For syntheses of related analogues, see: D. Marcoux et al. ­J. Med. Chem. 2019, 62, 9931; A. Karmakar et al. Org. Process Res. Dev. 2021, 25, 1001.


#

Comment

Highlights of the synthesis of BMS-986251 depicted are (1) a high-yielding four-step aza-Michael addition/mesylation/annulation sequence to form the tricyclic core, and (2) installation of the heptafluoroisopropyl moiety through a three-step carboxylation–bistrifluoromethylation–deoxyfluorination sequence.


#
#

Publication History

Article published online:
19 October 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany


   Permissions and Reprints