A Robust Process for an mGluR5 Negative Allosteric Modulator: Difluoromethylation and Sonogashira Coupling on Large Scale
Autor: | Jeffrey B. Sperry, Roger Farr, Varsolona Richard J, Levent Mahmut, Mousumi Ghosh, Steven M. Hoagland, Karen Sutherland |
---|---|
Rok vydání: | 2012 |
Předmět: | |
Zdroj: | Organic Process Research & Development. 16:1854-1860 |
ISSN: | 1520-586X 1083-6160 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |