Discovery of an Azabicyclo[2.1.1]hexane Piperazinium Salt and Its Application in Medicinal Chemistry via a Rearrangement

Org Lett. 2024 Jun 28;26(25):5318-5322. doi: 10.1021/acs.orglett.4c01696. Epub 2024 Jun 18.

Abstract

Herein we report the discovery of an azabicyclo[2.1.1]hexane piperazinium methanesulfonate salt from an unexpected rearrangement reaction in the preparation of ligand-directed degraders (LDDs). This bench-stable compound was found to be a versatile electrophile in a ring-opening reaction with various types of nucleophiles. Its utility as a versatile medicinal chemistry building block is further demonstrated in the synthesis of an LDD compound targeting degradation of the androgen receptor.

MeSH terms

  • Azabicyclo Compounds* / chemical synthesis
  • Azabicyclo Compounds* / chemistry
  • Chemistry, Pharmaceutical
  • Ligands
  • Molecular Structure
  • Piperazines* / chemical synthesis
  • Piperazines* / chemistry
  • Salts / chemistry

Substances

  • Piperazines
  • Azabicyclo Compounds
  • Ligands
  • Salts