The development of a practical and scalable synthetic route to BMT-773752-02, a key starting material for repotrectinib, is described. The original sequence exhibited various limitations such as use of pyrophoric organolithium reagents, low yield, poor diastereoselectivity, and lengthy workup/purification procedures, which were overcome by development of a new route. A salt screening was conducted to improve the physical properties of the title compound. The scalability of the newly designed synthetic strategy has been demonstrated on multihundred-kilogram scale production to afford greater than a metric ton of this intermediate.

中文翻译：

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通过 BMT-773752 的保护/去保护序列开发可扩展的烷基化：Repotrectinib 合成路线中的关键中间体

描述了 BMT-773752-02（repotrectinib 的关键起始材料）的实用且可扩展的合成路线的开发。原始序列表现出各种局限性，例如使用自燃有机锂试剂、产量低、非对映选择性差以及冗长的后处理/纯化程序，但通过开发新路线克服了这些局限性。进行盐筛选以改善标题化合物的物理性质。新设计的合成策略的可扩展性已在数百公斤规模的生产中得到证明，可以提供超过一吨的这种中间体。