Development of a Scalable Enantioselective Synthesis of JAK Inhibitor Upadacitinib
Development of a Scalable Enantioselective Synthesis of JAK Inhibitor Upadacitinib
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JAK 抑制剂 Upadacitinib 的可扩展对映选择性合成方法的开发
DOI：
10.1021/acs.oprd.1c00287
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发表时间：
2021
影响因子：
3.4
通讯作者：
Su Yu
中科院分区：
文献类型：
--
作者：
M. Rozema;L. Bhagavatula;Alan C. Christesen;Travis B. Dunn;Andrew R. Ickes;Brian Kotecki;J. C. Marek;Eric G. Moschetta;Westin H. Morrill;Mathew M. Mulhern;M. Rasmussen;Troy E. Reynolds;Su Yu
描述了JAK1抑制剂upadacitinib的六阶段合成过程。通过四取代烯烃的对映选择性和非对映选择性加氢来设置两个吡咯烷立体中心。讨论了主要片段的制备和连接策略，咪唑环化的优化，以及对最后阶段尿素部分形成的深入了解。
Process development of a six-stage synthesis of upadacitinib, a JAK1 inhibitor, is described. It is highlighted by an enantioselective and diastereoselective hydrogenation of a tetrasubstituted olefin to set the two pyrrolidine stereocenters. Preparation of the main fragments and strategies to link them together, optimization of the imidazole cyclization, and in-depth understanding of the formation of the urea moiety at the final stage are discussed.
影响因子：
2.6
作者：
Kuzmina, Olesya M.;Steib, Andreas K.;Knochel, Paul
通讯作者：
Knochel, Paul