The Synthesis of Two Potent β-3 Adrenergic Receptor Agonists

被引：27

作者：

Bradley, Paul A. ^{[1
]}

Carroll, Robert J. ^{[2
]}

Lecouturier, Yann C. ^{[1
]}

Moore, Robert ^{[2
]}

Noeureuil, Pierre ^{[1
]}

Patel, Bhairavi ^{[1
]}

Snow, Jonathan ^{[2
]}

Wheeler, Simon ^{[1
]}

机构：

[1] Discovery Chem, Global Res & Dev, Sandwich CT13 9NJ, Kent, England

[2] Res API, Pfizer Global Res & Dev, Sandwich CT13 9NJ, Kent, England

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2010年 / 14卷 / 06期

关键词：

POSSIBLE TOXIC ACTION; COMPUTER-PREDICTION; CHEMICAL-STRUCTURE; DEREK SYSTEM; REDUCTION; KETONES;

D O I：

10.1021/op1001462

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

This contribution describes the initial preparation of two potent beta-3 receptor agonists 1 and 2. Subsequent scale up of these two compounds was required for further evaluation and proceeded via a common key amine intermediate 24. Synthesis of this key intermediate by way of a Ritter reaction was a vital step in the sequence. Enantioselective Noyori hydrogenation reactions gave access to the chiral epoxides necessary to make the target compounds. Chemistry was developed for the selective dehalogenation of the 2-chloropyridyl group in the presence of a sensitive isoxazole unit to provide access to 1.

引用

页码：1326 / 1336

页数：11

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