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 UL, 0.21 mmol), and 3-methyl-3,9-diaza-spiro[5.5]undecane dihydrochloride (65.2 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 52 mg (77%) as a white powder. 1H-NMR (CD3OD, 500 MHz) δ 0.12-0.55 (m, 1H), 0.85-1.70 (m, 1H), 1.85 (m, 2H), 2.05-2.42 (m, 8H), 2.50 (s, 3H), 2.73-3.30 (m, 8H), 3.65 (bs, 1H), 4.00-4.43 (m, 2H), 5.46 (dd, J=7.6, 7.6, 1H), 7.07 (s, 1H), 7.17 (m, 1H), 7.27 (m, 1H), 7.38-7.46 (m, 2H), 7.50 (bs, 0.5H), 7.58 (m, 1H), 7.65 (bs, 0.5H), 7.96 (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 52 mg (77%) as a white powder