4-(Methylthio)phenylboronic acid → N1-(cyanomethyl)-N2-{[4-(methylsulfonyl)phenyl][4'-(methylthio)-1,1'-biphenyl-4-yl]methyl}-L-leucinamide

Participants

Reaction Conditions

Reaction Steps

A heterogeneous mixture of N2-{(4-bromophenyl)[4-(methylsulfonyl)phenyl]methyl}-N1-(cyanomethyl)-L-leucinamide from step 4 (72 mg, 0.15 mmol), 4-(methylthio)phenylboronic acid (37 mg, 0.22 mmol) in ethylene glycol dimethyl ether (1 mL) and 2M aqueous sodium carbonate was degassed under vacuum and purged with nitrogen. To this mixture was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), dichloromethane complex (19 mg, 0.023 mmol), followed by degassing and purging with nitrogen. The reaction mixture was heated at 85° C. for 16 hours with efficient stirring. The reaction mixture was partitioned between EtOAc and aqueous NH4OAc 25% w/v. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by chromatography using EtOAc and hexane as eluant to give the title compound as a colorless gum.

Provenance & Evidence