Oxadiazolone-Based Aromatic Annulations: A Nitrenoid Precursor for Tricyclic Aminoheterocycles

J Org Chem. 2024 Nov 1;89(21):15542-15552. doi: 10.1021/acs.joc.4c01622. Epub 2024 Oct 22.

Abstract

Nitrogen-containing heterocycles are present in most approved drugs, reflecting the significance of their synthetic strategies. By utilizing oxadiazolone as a nitrenoid (nitrene-like) precursor, we have developed a general strategy for the annulation with nucleophilic heterocycles to access various polycyclic aminoheterocycles. We have discovered that 2-pyrryl-substituted substrates undergo a rearrangement, which indicates a spirocyclization-migration pathway. Given their fluorescence and biological activity as kinase hinge binders, these fragment-like aminoheterocycles represent potential starting points for applications in chemical biology and drug discovery.

MeSH terms

  • Cyclization
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / chemistry
  • Molecular Structure
  • Oxadiazoles* / chemistry

Substances

  • Oxadiazoles
  • Heterocyclic Compounds