To a solution of methyl (S)-3-methyl-1-oxo-1-((1R,3S,5R)-3-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexan-2-yl)butan-2-ylcarbamate (0.60 g, 1.1 mmol) and (2S,4S)-tert-butyl 2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (0.46 g, 1.0 mmol) in DME (5 mL) was added Pd(PPh3)4 (0.08 g, 0.07 mmol) and K3PO4 (2M aqueous, 1.5 mL, 3.0 mmol). The resulting solution was degassed with argon for 5 min and heated to 80° C. (external temperature, oil bath) for 18 h. The reaction mixture was then cooled to room temperature and diluted with MeOH and CH2Cl2. The solution was washed with H2O and brine, and the aqueous layers were back extracted with CH2Cl2 and MeOH (˜10:1). The organic layers were combined and dried over Na2SO4 and concentrated. The crude oil was purified by silica gel chromatography (30 to 100% EtOAc (10% MeOH)/Hexanes to 80% MeOH/EtOAc) to provide (2S,4S)-tert-butyl 2-(2′-((1R,3S,5R)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H,1′H-7,7′-binaphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (0.79 g, 71%). LCMS-ESI+: calc'd for C45H51N7O6: 785.39 (M+); Found: 786.61 (M+H+).
