Development of an Early Enabling Synthesis for PF-03052334-02: A Novel Hepatoselective HMG-CoA Reductase Inhibitor

Autor:	David C. Boyles, Stephanie Schuyler, Edward J. Hessler, Jeffrey A. Pfefferkorn, Daniel Merritt Bowles, Chulho Choi
Rok vydání:	2010
Předmět:	Active ingredient Ozonolysis biology Stereochemistry Organic Chemistry Pyrazole Reductase chemistry.chemical_compound chemistry Yield (chemistry) Wittig reaction HMG-CoA reductase biology.protein Physical and Theoretical Chemistry Salt formation
Zdroj:	Organic Process Research & Development. 15:148-157
ISSN:	1520-586X 1083-6160
Popis:	Early process development work toward a promising pyrazole-based HMG-CoA reductase inhibitor is described. PF-03052334-02 (1) was prepared in 14 synthetic steps with a 21% overall yield, highlighted by a modified three-step hydroxypyrazole formation in which the yield was improved from 37% to 73%, a Suzuki/ozonolysis pathway that streamlined the downstream chemistry, and a reversed Wittig olefination strategy that improved the key coupling step from 50% to 95% yield. Multiple process hazards and most chromatography steps were removed, and a highly effective active pharmaceutical ingredient (API) salt formation, purification, and isolation protocol was also developed.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::3244cefc6fb774fd450882bea2ca9fe2 https://doi.org/10.1021/op100268e Zobrazit plný text záznamu