A Convergent Process for the Preparation of Adamantane 11-β-HSD-1 Inhibitors

被引：14
|
作者：
Becker, Calvin L. [1 ]
Engstrom, Kenneth M. [1 ]
Kerdesky, Francis A. [1 ]
Tolle, John C. [1 ]
Wagaw, Seble H. [1 ]
Wang, Weifeng [1 ]
机构：
[1] Abbott Labs, Dept R450, N Chicago, IL 60064 USA
来源：
ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2008年 / 12卷 / 06期
关键词：
D O I：
10.1021/op800065q
中图分类号：
O69 [应用化学];
学科分类号：
081704 ;
摘要：
A convergent, scalable process was developed for the synthesis of adamantane 11-beta-hydroxysteroid dehydrogenase-1 inhibitors E-4(2-methyl-2-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)propionylamino)adamantane-1-carboxylic acid (1) and E-4-(2-methyl-2-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)propionylamino)- adamantane-1-carboxamide (2) to rapidly deliver material for development. The process was high yielding and provided I in 52% overall yield over six total steps with a five-step longest linear sequence and 2 in 45% overall yield over seven total steps with a six-step longest linear sequence. A process to prepare active pharmaceutical ingredient (API) of >99% purity at the kilogram scale has been developed under tight delivery timelines.
引用
收藏
页码：1114 / 1118
页数：5
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