Development of an Effective Palladium Removal Process for VEGF Oncology Candidate AG13736 and a Simple, Efficient Screening Technique for Scavenger Reagent Identification

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• 作者：Erik J. Flahive ; Brigitte L. Ewanicki ; Neal W. Sach ; Stacy A. O’ ; Neill-Slawecki ; Nebojsa S. Stankovic ; Shu Yu ; Steven M. Guinness ; Jonathan Dunn
• 刊名：Organic Process Research & Development
• 出版年：2008
• 出版时间：July 2008
• 年：2008
• 卷：12
• 期：4
• 页码：637-645
• 全文大小：209K
• 年卷期：v.12,no.4(July 2008)
• ISSN：1520-586X

文摘

AG13736 (Axitinib), an inhibitor of vascular endothelial growth factor (VEGF) under investigation as an oncology drug, is currently manufactured via a three-step process that utilizes two palladium-mediated cross-couplings. Historically, removal of residual heavy metals from the active pharmaceutical ingredient has been a persistent issue. The development of a much improved process for palladium removal and a useful screening technique developed to rapidly identify the most efficient reagents for this purpose are outlined. The performance of the new endgame process in pilot-plant scale-up is also discussed.