Reaction Steps
T3P (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) was added to a solution of 7-(ethyloxy)-6-(ethylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.200 g, 0.315 mmol), (1R)-2,2,2-trifluoro-1-phenylethanamine (0.087 g, 0.409 mmol), N,N-diisopropylethylamine (10.99 μL, 0.063 mmol) in dichloromethane (4 mL) at 0° C. The mixture was stirred at 0° C. for 2 h, warmed to room temperature, and stirred overnight. The solution was 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 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 methylene chloride (three times). The combined organic extracts were washed with brine (two times), dried over Na2SO4, filtered, and concentrated in vacuo to afford 7-(ethyloxy)-6-(ethylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.165 g, 63% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ9.75 (br. s., 1H), 8.77 (s, 1H), 7.81 (s, 1H), 7.74-7.79 (m, 1H), 7.62-7.70 (m, 2H), 7.52-7.59 (m, 3H), 7.40-7.50 (m, 3H), 6.25 (br. s., 1H), 4.29-4.39 (m, 2H), 3.64-3.71 (m, 4H), 3.53-3.64 (m, 2H), 3.48 (q, J=7.03 Hz, 2H), 2.63 (br. s., 1H), 2.37-2.46 (m, 4H), 2.22 (br. s., 1H), 1.97-2.09 (m, 1H), 1.67 (br. s., 4H), 1.58 (t, J=6.90 Hz, 3H), 1.50 (br. s., 1H), 1.31 (t, J=7.40 Hz, 3H), 1.08-1.24 (m, 1H); MS (m/z) 793.2 (M+H+).
