Multigram Preparation of BRD4780 Enantiomers and Assignment of Absolute Stereochemistry

J Org Chem. 2021 Mar 5;86(5):4281-4289. doi: 10.1021/acs.joc.0c02520. Epub 2021 Feb 22.

Abstract

The development of a multigram synthesis of 3-exo-isopropylbicyclo[2.2.1]heptan-2-endo-amine hydrochloride (1) (also known as BRD4780 and AGN-192403) is described. The process involves protection of the amine as 4-nitrobenzyl carbamate, pNZ, which enables chiral SFC chromatography. The absolute configuration (AC) of the individual enantiomers has been determined by Mosher's amide method, VCD spectroscopy, and X-ray crystallography. We highlight the VCD approach as a rapid and effective means of AC determination that can be deployed directly on the target compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides*
  • Circular Dichroism
  • Crystallography, X-Ray
  • Stereoisomerism

Substances

  • Amides