Described herein is the discovery and development of a process to prepare chiral triazinanone R-3 and diastereomeric intermediate 5, the key intermediates in the synthesis of the cap-dependent endonuclease inhibitor baloxavir marboxil (1), which can suppress the replication of influenza virus. Chiral triazinanone R-3 was obtained via optical resolution of its racemic form rac-3. Diastereomeric intermediate 5 was obtained by the condensation reaction of triazinanone R-3 and thiepin alcohol 4 using a combination of T3P and MsOH. These reactions were performed successfully on kilogram scale and were critical to the establishment of the baloxavir marboxil manufacturing process.

中文翻译：

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Baloxavir Marboxil 合成的第一代工艺开发：制备 Baloxavir Marboxil 中间体的合成方法的早期开发


本文描述的是制备手性三嗪酮 R-3 和非对映异构体中间体 5 的方法的发现和开发，这是合成帽依赖性核酸内切酶抑制剂 baloxavir marboxil (1) 的关键中间体，可抑制流感病毒的复制。手性三嗪酮 R-3 通过光学拆分其外消旋形式 rac-3 获得。使用T3P和MsOH的组合，通过三嗪酮R-3和硫杂苯醇4的缩合反应得到非对映体中间体5。这些反应在公斤级上成功进行，对于巴洛沙韦马波西生产工艺的建立至关重要。