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：

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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。