Mild and Efficient Palladium-Mediated C-N Cross-Coupling Reaction between DNA-Conjugated Aryl Bromides and Aromatic Amines

ACS Comb Sci. 2019 Feb 11;21(2):69-74. doi: 10.1021/acscombsci.8b00142. Epub 2019 Jan 10.

Abstract

DNA-encoded library technology (ELT) has emerged in the pharmaceutical industry as a powerful tool for hit and lead generation. Over the last 10 years, a number of DNA-compatible chemical reactions have been published and used to synthesize libraries. Among the most commonly used reactions in medicinal chemistry is the C-N bond formation, and its application to DNA-encoded library technology affords an alternative approach to identify high-affinity binders for biologically relevant protein targets. Herein we report a newly developed Pd-promoted C-N cross coupling reaction between DNA-conjugated aryl bromides and a wide scope of arylamines in good to excellent yields. The mild reaction conditions should facilitate the synthesis of novel DNA-encoded combinatorial libraries.

Keywords: C−N bond formation; DNA-encoded chemical libraries.

MeSH terms

  • Amines / chemistry*
  • Catalysis
  • Combinatorial Chemistry Techniques / methods
  • DNA / chemistry*
  • Hydrocarbons, Aromatic / chemistry*
  • Hydrocarbons, Brominated / chemistry*
  • Organometallic Compounds / chemistry*
  • Palladium / chemistry*
  • Small Molecule Libraries / chemistry

Substances

  • Amines
  • Hydrocarbons, Aromatic
  • Hydrocarbons, Brominated
  • Organometallic Compounds
  • Small Molecule Libraries
  • Palladium
  • DNA