Asymmetric Hydroboration Approach to the Scalable Synthesis of ((1R,3S)-1-Amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986104) as a Potent S1P1 Receptor Modulator PMID: 28002964

Target-related Cytokines

2026-09-23

Asymmetric Hydroboration Approach to the Scalable Synthesis of ((1R,3S)-1-Amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986104) as a Potent S1P1 Receptor Modulator

J Med Chem. 2016 Dec 22;59(24):11138-11147. doi: 10.1021/acs.jmedchem.6b01433.

Michael G Yang ¹ , Zili Xiao ¹ , T G Murali Dhar ¹ , Hai-Yun Xiao ¹ , John L Gilmore ¹ , David Marcoux ¹ , Jenny H Xie ¹ , Kim W McIntyre ¹ , Tracy L Taylor ¹ , Virna Borowski ¹ , Elizabeth Heimrich ¹ , Yu-Wen Li ¹ , Jianlin Feng ¹ , Alda Fernandes ¹ , Zheng Yang ¹ , Praveen Balimane ¹ , Anthony M Marino ¹ , Georgia Cornelius ¹ , Bethanne M Warrack ¹ , Arvind Mathur ¹ , Dauh-Rurng Wu ¹ , Peng Li ¹ , Anuradha Gupta ¹ , Bala Pragalathan ¹ , Ding Ren Shen ¹ , Mary Ellen Cvijic ¹ , Lois D Lehman-McKeeman ¹ , Luisa Salter-Cid ¹ , Joel C Barrish ¹ , Percy H Carter ¹ , Alaric J Dyckman ¹

Affiliations

Abstract

We describe a highly efficient route for the synthesis of 4a (BMS-986104). A key step in the synthesis is the asymmetric hydroboration of trisubstituted alkene 6. Particularly given the known difficulties involved in this type of transformation (6 → 7), the current methodology provides an efficient approach to prepare this class of compounds. In addition, we disclose the efficacy of 4a in a mouse EAE model, which is comparable to 4c (FTY720). Mechanistically, 4a exhibited excellent remyelinating effects on lysophosphatidylcholine (LPC) induced demyelination in a three-dimensional brain Cell Culture assay.