依鲁替尼合成研究进展

Research advances in the synthesis of ibrutinib

依鲁替尼是一种近年上市的靶向抗癌新药,可用于套细胞淋巴瘤(MCL)的治疗。本文对文献报道的依鲁替尼的合成方法进行归纳和讨论,旨在为依鲁替尼新合成工艺研发提供参考。依鲁替尼的合成主要包括以Mitsunobu/取代反应为关键步骤的合成方案;以金属催化的偶联反应为关键反应的合成路线;以不同方法引入丙烯酰基的合成方案以及其他类型的合成路线。

Ibrutinib is a new anticancer drug used in the treatment of mantle cell lymphoma （MCL）. This review summarized the synthetic methods of ibrutinib reported in the literature and aimed to provide a reference for the research and development of new ibrutinib synthetic technology. The key steps in synthesis of ibrutinib were organized in four categories：Mitsunobu reaction or SN2 reaction, transition-metal catalyzed cross-coupling reaction, different strategies of acryloyl group introduction in the final stage, and other types of synthetic routes.