Synthesis of Selective Estrogen Receptor Degrader GDC-0810 via Stereocontrolled Assembly of a Tetrasubstituted All-Carbon Olefin
Synthesis of Selective Estrogen Receptor Degrader GDC-0810 via Stereocontrolled Assembly of a Tetrasubstituted All-Carbon Olefin
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DOI：
10.1021/acs.joc.8b01551
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发表时间：
2018-10-05
影响因子：
3.6
通讯作者：
Gosselin, Francis
中科院分区：
文献类型：
--
作者：
Savage, Scott;McClory, Andrew;Gosselin, Francis
We report an efficient synthesis of GDC-0810 on the basis of a sequence involving a highly stereoselective lithium tert-butoxide-mediated enolization tosylation (>= 95:5 E:Z) and a Pd-catalyzed Suzuki Miyaura cross-coupling as key steps. Global deprotection, pyrrolidine salt formation, and final active pharmaceutical ingredient (API) form control/isolation produced GDC-0810 free acid in a 40% overall yield with >99.0% purity as ascertained by HPLC analysis.
