Synthesis of Selective Estrogen Receptor Degrader GDC-0810 via Stereocontrolled Assembly of a Tetrasubstituted All-Carbon Olefin.

Authors :: Savage S
McClory A
Zhang H
Cravillion T
Lim NK
Masui C
Robinson SJ
Han C
Ochs C
Rege PD
Gosselin F
Source :: The Journal of organic chemistry [J Org Chem] 2018 Oct 05; Vol. 83 (19), pp. 11571-11576. Date of Electronic Publication: 2018 Sep 20.
Publication Year :: 2018
Abstract: 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.

Subjects :: Chemistry Techniques, Synthetic
Cinnamates pharmacology
Indazoles pharmacology
Ketones chemistry
Stereoisomerism
Alkenes chemistry
Carbon chemistry
Cinnamates chemical synthesis
Cinnamates chemistry
Indazoles chemical synthesis
Indazoles chemistry
Receptors, Estrogen metabolism

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