Development and Manufacture of the Inosine Monophosphate Dehydrogenase Inhibitor Merimepodib, VX-497

Autor:	Ansell Graham, Todd A. Blythe, Benjamin J. Littler, Minzhang Chen, John R. Snoonian, Looker Adam, Bobbianna J. Neubert, Phil Nyce, Jones Andrew D
Rok vydání:	2008
Předmět:	Reaction conditions chemistry.chemical_compound Hplc analysis Chromatography Merimepodib chemistry IMP dehydrogenase Organic Chemistry Organic chemistry Physical and Theoretical Chemistry Phosgene Inosine Monophosphate Dehydrogenase Inhibitor
Zdroj:	Organic Process Research & Development. 12:666-673
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op800060h
Popis:	A process for the manufacture of merimepodib (VX-497), an inosine monophosphate dehydrogenase (IMPDH) inhibitor, has been developed and efficiently scaled to produce clinical supply. The process comprises five steps, incorporating simple and robust chemistry that ultimately yielded 96.5 kg with a purity of 100% (by HPLC analysis) and 99.7% w/w assay. Highlights of the process are the effective use of production-scale phosgene, manipulation of Schotten−Baumann reaction conditions to give a low pH procedure that avoids a critical impurity, and the use of online tools to better identify parameters of the API purification.
Databáze:	OpenAIRE
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