Process Development and Optimization for Production of a Potassium Ion Channel Blocker, ICA-17043

Autor:	Kerry Spear, Sripathy Venkatraman, Bingidimi I. Mobele, Cameron Gibb, Brian E. Marron, Grant Andrew Mcnaughton-Smith, Stephen M. Shaw, Mark J. Suto, Luckner Ulysse, Carl A. Lindmark
Rok vydání:	2012
Předmět:	Active ingredient Hydrolysis chemistry.chemical_compound Chromatography Nitrile Chemistry Process development Organic Chemistry Grignard reaction Physical and Theoretical Chemistry Cyanation High-performance liquid chromatography Potassium channel
Zdroj:	Organic Process Research & Development. 16:1385-1392
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op3000916
Popis:	A scalable process for the manufacture of a potassium ion channel blocker was developed and optimized. Key features of the process include an optimized Grignard reaction, a direct cyanation of the intermediate trityl alcohol derivative, and an improved nitrile hydrolysis protocol, relative to the original acidic hydrolysis conditions, to generate the crude active pharmaceutical ingredient (API) with >95% HPLC purity. The Grignard and the cyanation reactions could be telescoped, resulting in an improved throughput compared to the original four-step process. An effective recrystallization of the API was also developed and the process scaled up to manufacture multiple batches at the pilot scale.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::aa05b07efe10cd64afabcfffab98010f https://doi.org/10.1021/op3000916 Zobrazit plný text záznamu