A Scalable Synthesis of an Azabicyclooctanyl Derivative, a Novel DPP-4 Inhibitor

被引：23

作者：

Fei, Zhongbo ^{[2
]}

Wu, Quanbing ^{[2
]}

Zhang, Fei ^{[2
]}

Cao, Yudong ^{[2
]}

Liu, Chuanqin ^{[2
]}

Shieh, Wen-Chung ^{[1
]}

Xue, Song ^{[1
]}

McKenna, Joe ^{[1
]}

Prasad, Kapa ^{[1
]}

Prashad, Mahavir ^{[1
]}

Baeschlin, Daniel ^{[3
]}

Namoto, Kenji ^{[3
]}

机构：

[1] Novartis Pharmaceut, Chem & Analyt Dev, E Hanover, NJ 07936 USA

[2] Suzhou Novartis Pharma Technol Co Ltd, Chem & Analyt Dev, Changshu 215537, Jiangsu, Peoples R China

[3] Novartis Inst Biomed Res, Ctr Prote Chem, CH-4002 Basel, Switzerland

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2008年 / 73卷 / 22期

关键词：

D O I：

10.1021/jo801830x

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A practical synthetic strategy to a chiral azabicycclooctanyl derivative (1), a potent DPP-4 inhibitor, starting from a commercially available nortropine is described. The stereogenic center of 1 was established employing a modified protocol of Ellman's diastereoselective addition of a benzylic nucleophile to tert-butanesulfinimme. Other key steps include Corey-Chaykovsky reaction, Meinwald rearrangement, and CDMT-promoted amide bond formation involving a sterically hindered amine 2.

引用

页码：9016 / 9021

页数：6

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