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:	Allosteric modulator Chemistry Scale (chemistry) Scientific method Organic Chemistry Sonogashira coupling Physical and Theoretical Chemistry Key features Photochemistry Combinatorial chemistry
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:	https://explore.openaire.eu/search/publication?articleId=doi_________::e6dd3c8876cd20aa8c502cdeae641b93 https://doi.org/10.1021/op3002728 Zobrazit plný text záznamu