Synthesis of Verubecestat, a BACE1 Inhibitor for the Treatment of Alzheimer's Disease

被引：35

作者：

Thaisrivongs, David K. ^{[1
]}

Miller, Steven P. ^{[1
]}

Molinaro, Carmela ^{[1
]}

Chen, Qinghao ^{[1
]}

Song, Zhiguo J. ^{[1
]}

Tan, Lushi ^{[1
]}

Chen, Lu ^{[3
]}

Chen, Wenyong ^{[1
]}

Lekhal, Azzeddine ^{[2
]}

Pulicare, Sarah K. ^{[2
]}

Xu, Yanke ^{[2
]}

机构：

[1] Merck Res Labs, Proc Chem, POB 2000, Rahway, NJ 07065 USA

[2] Merck Res Labs, Chem Engn Res & Dev, Proc Res & Dev, POB 2000, Rahway, NJ 07065 USA

[3] WuXi AppTec Shanghai Pharmaceut Co Ltd, 288 Fute Zhong Rd, Shanghai 200131, Peoples R China

来源：

ORGANIC LETTERS | 2016年 / 18卷 / 22期

关键词：

EFFICIENT COPPER CATALYST; ARYL HALIDES; AMIDATION; AMINES;

D O I：

10.1021/acs.orglett.6b01793

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Verubecestat is an inhibitor of beta-secretase being evaluated for the treatment of Alzheimer's disease. The first generation route relies on an amide coupling with a functionalized aniline, the preparation of which introduces synthetic inefficiencies. The second-generation route replaces this with a copper-catalyzed C-N coupling, allowing for more direct access to the target. Other features of the new route include a diastereoselective Mannich-type addition into an Ellman sulfinyl ketimine and a late-stage guanidinylation.

引用

页码：5780 / 5783

页数：4

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