- A robust process for an mGluR5 negative allosteric modulator: Difluoromethylation and sonogashira coupling on large scale
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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.
- Sperry, Jeffrey B.,Farr, Roger M.,Levent, Mahmut,Ghosh, Mousumi,Hoagland, Steven M.,Varsolona, Richard J.,Sutherland, Karen
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p. 1854 - 1860
(2013/01/15)
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- 2,3-DIHYDRO-1H-ISOINDOL-1-IMINE DERIVATIVES USEFUL AS THROMBIN PAR-1 RECEPTOR ANTAGONIST
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The present invention is directed to novel 2,3-dihydro-1H-isoindol-1-imine derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by the thrombin PAR-1 receptor antagonists.
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Page/Page column 32
(2011/05/08)
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- Reaction safety: A critical parameter in the development of a scaleable synthesis of 2,3-bis-chloromethylpyridine hydrochloride
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This report describes the development of a scaleable process to prepare 2,3-bis(chloromethyl)pyridine hydrochloride, 2, that is safe, economical, and environmentally acceptable. On a small scale this material is prepared using thionyl chloride as the solv
- Grimm,Maryanoff,Patel,Palmer,Sorgi,Stefanick,Webster,Zhang
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p. 938 - 942
(2013/09/06)
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