Multigram Preparation of BRD4780 Enantiomers and Assignment of Absolute Stereochemistry.
Brian T ChamberlainMathilde VincentJordan NafiePeter MüllerAnna GrekaFlorence F WagnerPublished in: The Journal of organic chemistry (2021)
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.
Keyphrases
- capillary electrophoresis
- mass spectrometry
- high resolution
- molecularly imprinted
- liquid chromatography
- solid phase extraction
- tandem mass spectrometry
- high speed
- high performance liquid chromatography
- single molecule
- dual energy
- loop mediated isothermal amplification
- ionic liquid
- computed tomography
- simultaneous determination
- magnetic resonance
- contrast enhanced