Development of a Scalable Asymmetric Process for the Synthesis of GLYT1 Inhibitor BI 425809 (Iclepertin)

This is the authors' abstract. We don't add key points for this paper.

A robust and scalable synthesis process for BI 425809 ( Iclepertin ), a GLYT1 inhibitor with potential therapeutic properties for the treatment of central nervous system disorders, was developed and implemented on a multikilogram scale. Key aspects of the process include the efficient asymmetric synthesis of intermediate 3-((1 R,5 R )-3-azabicyclo[3.1.0]hexan-1-yl)-5-(trifluoromethyl)isoxazole·HCl from raw materials readily available in bulk and the synthesis of ( R )-5-(methylsulfonyl)-2-((1,1,1-trifluoropropan-2-yl)oxy)benzoic acid through a novel Rh-catalyzed asymmetric hydrogenation.