Trifluoroacetic acid → FT-1101 free base
反応式
FC(F)(F)C(O)=O.[CH:8]1([O:12][C:13]2[C:22]([C:23]3[CH:24]=[N:25][N:26]([CH:28]4[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]4)[CH:27]=3)=[CH:21][CH:20]=[C:19]3[C:14]=2[CH2:15][CH2:16][C@H:17]([CH3:46])[N:18]3[C:41]([CH:43]2[CH2:45][CH2:44]2)=[O:42])[CH2:11][CH2:10][CH2:9]1>ClCCl>[CH:8]1([O:12][C:13]2[C:22]([C:23]3[CH:24]=[N:25][N:26]([CH:28]4[CH2:29][CH2:30][NH:31][CH2:32][CH2:33]4)[CH:27]=3)=[CH:21][CH:20]=[C:19]3[C:14]=2[CH2:15][CH2:16][C@H:17]([CH3:46])[N:18]3[C:41]([CH:43]2[CH2:45][CH2:44]2)=[O:42])[CH2:11][CH2:10][CH2:9]1参加物
4
実験手順
Trifluoroacetic acid (0.5 mL, 6.49 mmol) was added to a 0° C. solution of (S)-tert-butyl 4-(4-(5-cyclobutoxy-1-(cyclopropanecarbonyl)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.032 g, 0.060 mmol) in dichloromethane (2.0 mL). The ice bath was removed, and the mixture stirred at rt for 1.5 h. The reaction mixture was concentrated, and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The layers were separated and the organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to afford (S)-(5-cyclobutoxy-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone (0.022 g, 85%) as an off-white solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.57-0.71 (m, 1H), 0.78-0.91 (m, 1H), 0.92-1.04 (m, 1H), 1.13 (d, J=6.45 Hz, 3H), 1.19-1.45 (m, 3H), 1.53-1.71 (m, 2H), 1.79-2.42 (m, 11H), 2.74-2.92 (m, 2H), 2.94-3.09 (m, 1H), 3.30 (br d, J=12.61 Hz, 2H), 4.04-4.21 (m, 1H), 4.28 (ddt, J=11.43, 7.62, 3.96, 3.96 Hz, 1H), 4.66-4.84 (m, 1H), 7.12 (d, J=8.21 Hz, 1H), 7.28 (d, J=8.21 Hz, 1H), 7.81 (s, 1H), 7.88 (s, 1H). MS (ESI, pos. ion) m/z 435 [M+H]+.