Dichloromethane → (1S,2S,4S)-4-(2',4'-Difluoro-3-trifluoromethyl-biphenyl-4-sulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide

Participants

Reaction Conditions

Reaction Steps

Argon was bubbled through a mixture of (1R,2R,4R) and (1S,2S,4S)-4-(4-bromo-2-trifluoromethyl-benzenesulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide (30 mg, 0.0606 mmol, example 58), 2.4-difluorophenylboronic acid (11 mg, 0.0727 mmol) and Na2CO3 (17 mg, 0.1635 mmol) in DMF (1.5 ml) and water (81.8 ul) for 15 min. Then [1,1′-bis(diphenyl-phosphino)ferrocene]palladium(II) chloride 1:1 complex with DCM (5 mg, 0.00606 mmol) was added and the orange mixture was heated to 80° C. for 3 h. The mixture was then cooled to room temperature, poured onto a mixture of saturated NaHCO3 solution and ice and extracted 3 times with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and evaporated. The remaining brown solid was purified by silica gel chromatography (DCM/MeOH 98:2) to obtain the title compound (27 mg, 84%) as off-white solid. MS (EI): 529.2 (M+H)+.

Provenance & Evidence