Reaction Steps
A solution of 6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.220 g, 0.346 mmol), (1R)-2,2,2-trifluoro-1-phenylethanamine (0.095 g, 0.450 mmol), N,N-diisopropylethylamine (0.012 mL, 0.069 mmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane 2,4,6-trioxide (0.288 mL of a 50% solution in ethyl acetate, 0.485 mmol) in dichloromethane (4 mL) was stirred at 0° C. for 2 h. The reaction mixture was 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 twice 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 twice with brine, dried over Na2SO4, filtered, and concentrated in vacuo to afford 6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.218 g, 75% yield). 1H NMR (400 MHz, CDCl3) δ9.71 (br. s., 1H), 8.77 (s, 1H), 7.82 (s, 1H), 7.77 (d, J=6.78 Hz, 1H), 7.63-7.69 (m, 2H), 7.59 (s, 1H), 7.53-7.58 (m, 2H), 7.42-7.47 (m, 3H), 6.19-6.29 (m, 1H), 4.08 (s, 3H), 3.80 (quin, J=6.84 Hz, 1H), 3.64-3.71 (m, 4H), 3.53-3.64 (m, 2H), 2.62 (br. s., 1H), 2.38-2.46 (m, 4H), 2.16-2.27 (m, 1H), 2.03 (t, J=10.92 Hz, 1H), 1.56-1.71 (m, 3H), 1.47-1.56 (m, 1H), 1.36 (s, 3H), 1.34 (s, 3H), 1.22-1.32 (m, 1H), 1.08-1.22 (m, 1H); MS (m/z) 793.2 (M+H+).
