AMD070, a CXCR4 chemokine receptor antagonist: Practical large-scale laboratory synthesis

被引：35

作者：

Crawford, Jason B. ^{[1
]}

Chen, Gang ^{[1
]}

Gauthier, David ^{[1
]}

Wilson, Trevor ^{[1
]}

Carpenter, Bryon ^{[1
]}

Baird, Lan R. ^{[1
]}

McEachern, Ernie ^{[1
]}

Kaller, Alan ^{[1
]}

Harwig, Curtis ^{[1
]}

Atsma, Bem ^{[1
]}

Skerlj, Renato T. ^{[1
]}

Bridger, Gary J. ^{[1
]}

机构：

[1] AnorMED Inc, Langley, BC, Canada

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2008年 / 12卷 / 05期

关键词：

D O I：

10.1021/op8000993

中图分类号：

O69 [应用化学];

学科分类号：

081704 [应用化学];

摘要：

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 I in a pure crystalline form.

引用

页码：823 / 830

页数：8

共 34 条

[1]

Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures [J].