反应详情

温度

0 °C

To a solution of (R)-3-(7-methyl-1H-indazol-5-yl)-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carbonyloxy)propanoic acid (50 mg, 0.11 mmol), diisopropylethylamine (37 μL, 0.21 mmol), and 1-cyclohexylpiperazine (35.5 mg, 2.0 equiv) in dimethylformamide (0.50 mL) and dichloromethane (0.50 mL) at 0° C. was added PyBOP® (57.6 mg, 0.11 mmol). The reaction was stirred at 0° C. for 4 h. The reaction was concentrated and purified by column chromatography (95:5:1 to 90:10:1 dichloromethane/methanol/triethylamine). The resulting residue was dissolved in 5% methanol/dichloromethane and passed through a basic alumina column to give 62.3 mg (92%) as a white powder. 1H-NMR (CD3OD, 500 MHz) δ 0.75-2.10 (m, 20H), 2.29 (m, 1H), 2.47 (m, 1H), 2.56 (s, 3H), 2.77-3.41 (m, 9H), 3.73 (m, 1H), 4.04-4.49 (m, 2H), 5.52 (dd, J=8.2, 7.3, 1H), 7.11 (s, 1H), 7.22 (dd, J=7.0, 7.0, 1H), 7.33 (d, J=7.9, 1H), 7.42-7.53 (m, 2H), 7.53-7.76 (m, 2H), 8.01 (s, 1H). Mass spec.: 625.33 (MH)+.

1. concentrationThe reaction was concentrated
2. custompurified by column chromatography (95:5:1 to 90:10:1 dichloromethane/methanol/triethylamine)
3. dissolutionThe resulting residue was dissolved in 5% methanol/dichloromethane
4. customto give 62.3 mg (92%) as a white powder