Process Development for ABT-472, a Benzimidazole PARP Inhibitor

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• 作者：Jufang H. Barkalow ; Jeffrey Breting ; Bruce J. Gaede ; Anthony R. Haight ; Rodger Henry ; Brian Kotecki ; Jianzhang Mei ; Kurt B. Pearl ; Jason S. Tedrow ; Shekhar K. Viswanath
• 刊名：Organic Process Research & Development
• 出版年：2007
• 出版时间：July 2007
• 年：2007
• 卷：11
• 期：4
• 页码：693 - 698
• 全文大小：112K
• 年卷期：v.11,no.4(July 2007)
• ISSN：1520-586X

文摘

A nine-step convergent process was developed for the synthesisof ABT-472, a benzimidazole PARP inhibitor. The identity andorigin of several impurities were determined, and the processwas modified to reduce or eliminate these impurities. A numberof safety and control issues were investigated. The originalsynthesis was shortened to 9 steps and streamlined whilemaintaining a convergent strategy. A stable salt was selected,and control of the API solid form was established. The processwas successfully scaled up to provide 8.5 kg of final product of>99% purity in 33% yield over 9 steps.