Reaction Steps
A solution of 7-[(1-methylethyl)oxy]-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.200 mg, 0.315 mmol), (1R)-2,2,2-trifluoro-1-phenylethanamine (0.072 g, 0.409 mmol), N,N-diisopropylethylamine (10.99 μL, 0.063 mmol), and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane 2,4,6-trioxide (0.262 mL of a 50% solution in ethyl acetate, 0.440 mmol) in dichloromethane (2 mL) was stirred at 0° C. for 2 h. The solution was warmed to room temperature overnight, diluted with saturated aqueous NaHCO3, and extracted with methylene chloride (three times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via HPLC (Waters, Sunfire 30×100 mm, 25-60% CH3CN/H2O with 0.1% TFA) to afford 7-[(1-methylethyl)oxy]-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.137 g, 52% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ9.85 (br. s., 1H), 8.79 (s, 1H), 7.81 (s, 1H), 7.75-7.80 (m, 1H), 7.64-7.69 (m, 2H), 7.52-7.59 (m, 3H), 7.42-7.48 (m, 3H), 6.25 (t, J=6.90 Hz, 1H), 4.91 (dt, J=6.02, 12.05 Hz, 1H), 3.65-3.72 (m, 5H), 3.52-3.65 (m, 2H), 3.31 (s, 3H), 2.64 (br. s., 1H), 2.38-2.45 (m, 4H), 2.20 (br. s., 1H), 2.03 (t, J=10.67 Hz, 1H), 1.66 (br. s., 4H), 1.59 (d, J=11.54 Hz, 2H), 1.54 (s, 3H), 1.53 (s, 3H); MS (m/z) 793.3 (M+H+).
