AMD070, a CXCR4 Chemokine Receptor Antagonist: Practical Large-Scale Laboratory Synthesis

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• 作者：Jason B. Crawford ; Gang Chen ; David Gauthier ; Trevor Wilson ; Bryon Carpenter ; Ian R. Baird ; Ernie McEachern ; Alan Kaller ; Curtis Harwig ; Bem Atsma ; Renato T. Skerlj ; Gary J. Bridger
• 刊名：Organic Process Research & Development
• 出版年：2008
• 出版时间：September 19, 2008
• 年：2008
• 卷：12
• 期：5
• 页码：823-830
• 全文大小：197K
• 年卷期：v.12,no.5(September 19, 2008)
• ISSN：1520-586X

文摘

An efficient and convergent four-step synthetic route to the CXCR4 chemokine receptor antagonist AMD070 (1) has been developed which employs only a single chromatographic step in the entire sequence. Novel reductive amination methods have been developed for the coupling of 2 and 3 in which a dehydrative imine formation is followed by reduction with an attenuated borohydride reagent (zinc chloride and sodium borohydride). Selective extraction methods were employed to purify synthetic intermediates and remove reagents and impurities. A procedure has also been developed to isolate 1 in a pure crystalline form.