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

页码：1114 / 1118

页数：5

共 15 条

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