Reaction Steps
7-(ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.200 g, 0.303 mmol), (1R)-2,2,2-trifluoro-1-phenylethanamine (0.069 g, 0.393 mmol), N,N-diisopropylethylamine (10.57 μL, 0.061 mmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane 2,4,6-trioxide (0.252 mL of a 50% solution in ethyl acetate, 0.424 mmol) in dichloromethane (2 mL) was stirred at 0° C. for 2 h. The solution was warmed to room temperature overnight. The solution was diluted with saturated aqueous NaHCO3 and extracted with methylene chloride (3 times). The combined organic extracts were washed with brine (two times), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was dissolved in DMSO and purified via HPLC (Waters, Sunfire, 30×75 mm column, 50 mL/min, 20-60% MeCN/H2O with 0.1% TFA). The fractions containing the product were neutralized with saturated aqueous NaHCO3 and extracted with CH2Cl2 (3 times). The combined organic extracts were washed with brine (2 times), dried over Na2SO4, filtered, and concentrated in vacuo to afford 7-(ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.086 g, 35% yield). 1H NMR (400 MHz, CDCl3) δ9.88 (br. s., 1H), 8.79 (s, 1H), 7.81 (s, 1H), 7.78 (d, J=6.02 Hz, 1H), 7.64-7.69 (m, 2H), 7.53-7.60 (m, 3H), 7.43-7.48 (m, 3H), 6.25 (quin, J=7.65 Hz, 1H), 4.36 (q, J=6.94 Hz, 2H), 3.66-3.71 (m, 4H), 3.53-3.65 (m, 2H), 3.33 (s, 3H), 2.64 (br. s., 1H), 2.38-2.46 (m, 4H), 2.20 (br. s., 1H), 2.04 (t, J=10.92 Hz, 1H), 1.56-1.66 (m, 9H); MS (m/z) 779.3 (M+H+).
