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

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  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 2985193R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6904 (Electronic) Linking ISSN: 00223263 NLM ISO Abbreviation: J Org Chem Subsets: MEDLINE
    • Publication Information:
      Publication: Columbus Oh : American Chemical Society
      Original Publication: Easton, Pa. [etc.]
    • Subject Terms:
      Alkenes/*chemistry ; Carbon/*chemistry ; Cinnamates/*chemical synthesis ; Cinnamates/*chemistry ; Indazoles/*chemical synthesis ; Indazoles/*chemistry ; Receptors, Estrogen/*metabolism; Chemistry Techniques, Synthetic ; Cinnamates/pharmacology ; Indazoles/pharmacology ; Ketones/chemistry ; Stereoisomerism
    • 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.
    • Accession Number:
      0 (3-(4-(2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid)
      0 (Alkenes)
      0 (Cinnamates)
      0 (Indazoles)
      0 (Ketones)
      0 (Receptors, Estrogen)
      7440-44-0 (Carbon)
    • Publication Date:
      Date Created: 20180912 Date Completed: 20190906 Latest Revision: 20190906
    • Publication Date:
      20221213
    • Accession Number:
      10.1021/acs.joc.8b01551
    • Accession Number:
      30200756