当前位置：
X-MOL 学术
›
Org. Process Res. Dev.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Synthesis, Optimization, and Large-Scale Preparation of the Low-Dose Central Nervous System-Penetrant BACE1 Inhibitor LY3202626 via a [3 + 2] Nitrone Cycloaddition
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2020-02-04 , DOI: 10.1021/acs.oprd.9b00471 Pablo Garcia-Losada 1 , Amy C. DeBaillie 2 , Jose Eugenio de Diego 1 , Steven J. Green 3 , Marvin M. Hansen 2 , Carlos Jaramillo 1 , Matt Johnson 4 , Talbi Kaoudi 1 , Jiuyuan Li 4 , Peter J. Lindsay-Scott 5 , Carlos Mateos 1 , Dustin J. Mergott 3 , Juan Antonio Rincon 1 , Roger R. Rothhaar 2 , Kevin D. Seibert 2 , Brian M. Watson 3 , Leonard L. Winneroski 3 , Srinivas Gangula 4 , Dajiang Jing 4 , Hao Sun 4 , Lei Zhang 4 , Michael O. Frederick 2
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2020-02-04 , DOI: 10.1021/acs.oprd.9b00471 Pablo Garcia-Losada 1 , Amy C. DeBaillie 2 , Jose Eugenio de Diego 1 , Steven J. Green 3 , Marvin M. Hansen 2 , Carlos Jaramillo 1 , Matt Johnson 4 , Talbi Kaoudi 1 , Jiuyuan Li 4 , Peter J. Lindsay-Scott 5 , Carlos Mateos 1 , Dustin J. Mergott 3 , Juan Antonio Rincon 1 , Roger R. Rothhaar 2 , Kevin D. Seibert 2 , Brian M. Watson 3 , Leonard L. Winneroski 3 , Srinivas Gangula 4 , Dajiang Jing 4 , Hao Sun 4 , Lei Zhang 4 , Michael O. Frederick 2
Affiliation
|
Herein we report a summary of the synthetic development of LY3202626 from the initial discovery route to a final route that was scaled to make 150 kg. Key developments include the use of a [3 + 2] cyclization to set the cis ring junction of the formed isoxazoline, a one-pot thiazine formation, and three different ways to install the aniline: (1) Cu-catalyzed azide coupling and reduction, (2) nitration and reduction, and (3) Buchwald coupling with acetamide.
中文翻译：
低剂量中枢神经系统渗透性BACE1抑制剂LY3202626的合成，优化和大规模制备，通过[3 + 2] Nitrone Cycloaddition
本文中，我们概述了LY3202626从最初的发现路线到最终制造成150千克最终路线的合成开发过程。关键的发展包括使用[3 + 2]环化来设置形成的异恶唑啉的顺式环结，一锅噻嗪的形成以及三种不同的苯胺安装方法：（1）铜催化的叠氮化物偶联和还原，（2）硝化和还原，以及（3）Buchwald与乙酰胺偶联。
更新日期：2020-02-04
中文翻译：
低剂量中枢神经系统渗透性BACE1抑制剂LY3202626的合成，优化和大规模制备，通过[3 + 2] Nitrone Cycloaddition
本文中，我们概述了LY3202626从最初的发现路线到最终制造成150千克最终路线的合成开发过程。关键的发展包括使用[3 + 2]环化来设置形成的异恶唑啉的顺式环结，一锅噻嗪的形成以及三种不同的苯胺安装方法：（1）铜催化的叠氮化物偶联和还原，（2）硝化和还原，以及（3）Buchwald与乙酰胺偶联。
京公网安备 11010802027423号