Copper-Mediated Aminoquinoline-Directed Radiofluorination of Aromatic C-H Bonds with K18 F

Angew Chem Int Ed Engl. 2019 Mar 4;58(10):3119-3122. doi: 10.1002/anie.201812701. Epub 2019 Jan 18.

Abstract

A Cu-mediated ortho-C-H radiofluorination of aromatic carboxylic acids that are protected as 8-aminoquinoline benzamides is described. The method uses K18 F and is compatible with a wide range of functional groups. The reaction is showcased in the high specific activity automated synthesis of the RARβ2 agonist [18 F]AC261066.

Keywords: C−H fluorination; C−H functionalization; PET radiochemistry; fluorine-18; late-stage fluorination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aminoquinolines / chemical synthesis
  • Aminoquinolines / chemistry*
  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzoates / chemical synthesis*
  • Benzoates / chemistry
  • Copper / chemistry*
  • Fluorine Radioisotopes / chemistry*
  • Halogenation
  • Humans
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry
  • Receptors, Retinoic Acid / agonists
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry

Substances

  • 4-(4-(2-(n-butoxy)ethoxy)-5-methylthiazol-2-yl)-2-fluorobenzoic acid
  • Aminoquinolines
  • Benzamides
  • Benzoates
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Retinoic Acid
  • Thiazoles
  • retinoic acid receptor beta
  • Copper
  • Fluorine-18
  • 8-aminoquinoline