Enantioselective synthesis of BMS-911278: a triple reuptake inhibitor

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• 作者：Jianqing Li^a ; ^{jianqing.li@bms.com} ; Daniel Smith^a ; Subramaniam Krishnananthan^a ; Dauh-Rurng Wu^a ; Dawn Sun^a ; Peng Li^a ; Kristen Ryan^b ; Min Hu^b ; Wenge Cui^b ; Jennifer Naginskaya^b ; Shuang Liu^b ; Paul C. Lobben^c ; Alicia T. Ng^d ; Richard Olson^d ; Arvind Mathur^a
• 刊名：Tetrahedron: Asymmetry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：28
• 期：1
• 页码：196-202
• 全文大小：776 K
• 卷排序：28

文摘

BMS-911278 was identified as a potent triple reuptake inhibitor potentially useful for the treatment of depression. The original racemic synthesis suffered from tedious and low recovery resolution and HPLC separation, as well as low-yielding hazardous N-demethylation at the API step. To support further preclinical studies, a scalable enantioselective synthesis was developed. Herein, we report an efficient asymmetric synthesis of BMS-911278 featuring two key steps: an enantioselective Miyaura reaction and an intramolecular regioselective cyclization.