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

作者：Mobele Bingidimi I; Venkatraman Sripathy^*; McNaughton Smith Grant; Gibb Cameron; Ulysse Luckner G; Lindmark Carl A; Shaw Stephen; Marron Brian; Spear Kerry; Suto Mark J

来源：Organic Process Research & Development, 2012, 16(8): 1385-1392.

DOI：10.1021/op3000916

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.

• 出版日期2012-8