Reaction Steps
T3P (2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane 2,4,6-trioxide, 0.253 mL of a 50% solution in ethyl acetate, 0.425 mmol) was added to a solution of 3-(1,4′-bipiperidin-1′-ylmethyl)-6-(ethylsulfonyl)-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.200 g, 0.304 mmol), (1R)-2,2,2-trifluoro-1-phenylethanamine (0.069 g, 0.395 mmol), N,N-diisopropylethylamine (10.60 μL, 0.061 mmol) in dichloromethane (2 mL) at 0° C. The mixture was stirred at 0° C. for 2 h, warmed to room temperature, and stirred overnight. The reaction mixture was diluted with saturated 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. 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 to afford 3-(1,4′-bipiperidin-1′-ylmethyl)-6-(ethylsulfonyl)-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.160 g, 65% yield). 1H NMR (400 MHz, DMSO-d6) δ 10.05 (br. s., 1H), 8.50 (br. s., 1H), 7.97 (br. s., 1H), 7.87 (d, J=7.53 Hz, 2H), 7.80 (s, 1H), 7.71-7.78 (m, 1H), 7.65 (br. s., 2H), 7.42-7.51 (m, 3H), 6.22 (quin, J=8.60 Hz, 1H), 4.10 (s, 3H), 3.40-3.61 (m, 3H), 3.12-3.27 (m, 1H), 2.05-2.44 (m, 6H), 1.58-1.82 (m, 2H), 1.03-1.52 (m, 12H), 0.77-1.00 (m, 2H); MS (m/z) 777.2 (M+H+).
