To a solution of tert-butyl 4-(4-(5-(3-(4-cyanophenyl)azetidine-1-carbonyl)-2-methylphenyl)-5-methyl-1H-imidazol-2-yl)piperidine-1-carboxylate (compound 182.3, 227 mg, 0.42 mmol) in CH2Cl2 (10 mL), was added trifluoroacetic acid (2 ml). The reaction was stirred for 1.5 hours and concentrated under reduced pressure. The reaction mixture was neutralized with 2 mL Na2CO3 (1M) to afford the crude intermediate after lyophilization. A mixture of 4-(1-(4-methyl-3-(4-methyl-2-(piperidin-4-yl)-1H-imidazol-5-yl)benzoyl)azetidin-3-yl)benzonitrile (185 mg, 0.42 mmol) and diisopropyl ethylamine (363 μL, 2.1 mmol) were dissolved in DMF (6 mL). Methyl chloroformate (36 μL, 0.46 mmol) was added and the mixture was stirred at room temperature for 1 hour. The reaction was concentrated, diluted with saturated NaH2PO4 (20 mL) and extracted with EtOAc (3×20 ml). The organic phase was washed by brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by preparative TLC with 10% methanol in dichloromethane and lyophilized to give 141 mg (67%, over 2 steps) of the title compound as a white solid. m/z (ES+) 498 (M+H)+.
