[Synthesis]
3-(1,4'-Bipiperidin-1'-ylmethyl)-7-bromo-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (2.5 g, 4.34 mmol) and 1-phenylcyclopropanamine (0.900 g, 5.42 mmol) were added to a 500 mL flask with HOBT (0.664 g, 4.34 mmol), EDC ( 3.74 g, 19.52 mmol), dichloromethane (45 mL) and N,N-diisopropylethylamine (7.57 mL, 43.4 mmol). The reaction mixture was heated to 60 °C and kept for 5 hours. After the reaction was completed, it was cooled to room temperature and saturated aqueous sodium bicarbonate solution (50 mL), water (50 mL) and dichloromethane (50 mL) were added. After stirring for 30 minutes, the two phases were separated and the aqueous phase was extracted three times with dichloromethane. The organic phases were combined, filtered through a phase separator, concentrated and purified by reversed-phase HPLC (Biotage, 0-100% CH3CN/water with 0.1% TFA). The fraction containing the target product was collected, transferred to a partition funnel and saturated aqueous NaHCO3 and dichloromethane were added. The organic phase was separated and the aqueous phase was extracted three more times with dichloromethane. The organic phases were combined and concentrated to give 3-(1,4'-bipiperidin-1'-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide (2.5 g, 83% yield).1H NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1H), 8.32 (d, J = 2.01 Hz , 1H), 7.95 (s, 1H), 7.80-7.90 (m, 3H), 7.69-7.76 (m, 1H), 7.67 (d, J = 8.78 Hz, 1H), 7.42-7.50 (m, 2H), 7.38 (t, J = 7.65 Hz, 2H), 7.24-7.30 (m, 1H), 3.43 (br.s. , 2H), 2.38 (d, J = 9.79 Hz, 2H), 2.24-2.35 (m, 3H), 1.94 (t, J = 10.92 Hz, 1H), 1.59 (t, J = 10.92 Hz, 2H), 1.37-1.47 (m, 5H), 1.33 (br.s., 6H), 0.89-1.03 (m, 2H). MS (m/z) 693.2 (M + H+). |