A Robust Process for an mGluR5 Negative Allosteric Modulator: Difluoromethylation and Sonogashira Coupling on Large Scale

The development of the potent and selective mGluR5 negative allosteric modulator (NAM) 1 is described. Key features in the process, which has been implemented on a multikilogram scale, include a high-temperature difluoromethylation reaction, a Sonogashira coupling, and careful control of residual Pd...

Full description

Saved in:
Bibliographic Details
Published in:Organic process research & development 2012-11, Vol.16 (11), p.1854-1860
Main Authors: Sperry, Jeffrey B, Farr, Roger M, Levent, Mahmut, Ghosh, Mousumi, Hoagland, Steven M, Varsolona, Richard J, Sutherland, Karen
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The development of the potent and selective mGluR5 negative allosteric modulator (NAM) 1 is described. Key features in the process, which has been implemented on a multikilogram scale, include a high-temperature difluoromethylation reaction, a Sonogashira coupling, and careful control of residual Pd and Cu in the final API. Due to the relative nonpolar nature of the intermediates, water-miscible solvents were employed in all four steps to allow for direct crystallizations upon reaction completion. In addition, several crystalline morphologies of the API were discovered, and the isolation of the desired form II will be discussed.
ISSN:1083-6160
1520-586X
DOI:10.1021/op3002728