A Design of Experiments Approach to a Robust Final Deprotection and Reactive Crystallization of IPI-926, A Novel Hedgehog Pathway Inhibitor
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- 作者：Theodore A. Martinot ; Brian C. Austad ; Alexandre C么t茅 ; Kristopher M. Depew ; Daniel Genov ; Louis Grenier ; Joseph Helble ; Andre Lescarbeau ; Somarajan Nair ; Martin Trudeau ; Priscilla White ; Lin-Chen Yu
- 刊名：Organic Process Research & Development
- 出版年：2015
- 出版时间：November 20, 2015
- 年：2015
- 卷：19
- 期：11
- 页码：1693-1702
- 全文大小：559K
- ISSN：1520-586X
文摘
A design of experiments (DoE) approach was taken to optimize purity and reaction yield of the final debenzylation and hydrochloride salt formation of IPI-926. The study involved a careful dissection of the different process steps to enable an independent investigation of these steps while ensuring that process streams were representative. The results enabled a streamlined process from the final chemical transformation to the salting and isolation and led to the elimination of variability in the process as well as a robust control of impurities. The optimized process was applied to production and demonstrated on the kilogram scale.