Sodium Carbonate → 1-[4'-((1S)-1-{[(1S)-1-({[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]amino}carbonyl)-2-methylpropyl]amino}-2,2,2-trifluoroethyl)biphenyl-4-yl]cyclopropanecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

To N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N-[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]-L-valinamide (1 eq) in DMF (0.1M) were added 1-[4-(dihydroxyboryl)phenyl]cyclopropanecarboxylic acid (1.2 eq), Pd(dppf)Cl2 (0.05 eq) and 2M aqueous sodium carbonate (3 eq). The mixture was degassed by nitrogen bubbling for 5 min and heated to 90° C. for 2 h. The reaction mixture was cooled and diluted with EtOAc and 3N HCl was added to acidify the reaction mixture to pH 5. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine and water, dried over Na2SO4 filtered and concentrated. The crude compound was purified by automated SiO2 flash chromatography system using solvent gradient of 40% EtOAc/Hex to 100% EtOAc/Hex.

Provenance & Evidence