Scalable Asymmetric Synthesis of the All Cis Triamino Cyclohexane Core of BMS-813160

J Org Chem. 2022 Feb 18;87(4):1996-2011. doi: 10.1021/acs.joc.1c01162. Epub 2021 Aug 6.


BMS-813160 is a pharmaceutical entity currently in development at Bristol Myers Squibb. Its defining structural feature is a unique chiral all cis triamino cyclohexane core. Medicinal and process chemistry groups at BMS have previously published synthesis strategies for chemotypes similar to the target molecule, but a streamlined approach amenable for longer-term supply was necessary. A new synthetic route was conceptualized, experimentally investigated, and determined to meet the criteria for efficiency that addressed key limitations of previous approaches. Adopting/optimizing the Trost asymmetric allylic amination desymmetrization methodology was a key tool used to produce a synthesis intermediate with high optical purity. In addition, developing a tandem Mannich-aza-Michael reaction to obviate the need for a Curtis/acylation sequence and a novel reductive amination/thermal lactamization to circumvent Freidinger-type pyrrolidone preparation are some of the synthesis improvements that enabled access to the target molecule to fulfill long-term supply requirements.

MeSH terms

  • Amination
  • Catalysis*
  • Pyrazoles
  • Stereoisomerism
  • Triazines


  • BMS-813160
  • Pyrazoles
  • Triazines