反应详情

A solution of (5-Chloro-3-methyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-piperidine-4-yl-amine (140 mg, 0.37 mmol) and N-(phenoxycarbonyl)hydroxylamine (112 mg, 0.74 mmol) in anhydrous THF (4 mL) was stirred for 16 hours at 70° C. The solution was then cooled and concentrated under reduced pressure and dried in vacuo. The crude material was purified by column chromatography with silica gel (50:1:0.1 CH2Cl2/MeOH/NH4OH) to give COMPOUND 308 as a white solid (82 mg, 51%). 1H NMR (CDCl3): δ 1.73 (q, 2H, J=11.1 Hz), 1.96 (s, 3H), 1.99 (br, 2H), 2.70 (br, 3H), 3.85 (s, 2H), 4.05 (d, 2H, J=13.2 Hz), 4.26 (s, 2H), 6.65 (br, 1H (Oh)), 6.81 (br s, 1H (NH)), 7.33 (s, 1H), 7.42 (t, 1H, J=7.2 Hz), 7.54 (d, 1H, J=4.8 Hz), 7.62 (t, 1H, J=7.8 Hz), 7.77 (d, 1H, J=7.8 Hz), 7.95 (d, 1H, J=7.2 Hz), 8.26 (s, 1H), 8.39 (d, 1H, J=3.6 Hz). 13C NMR (CDCl3) δ 18.75, 28.62 (2C), 45.17 (2C), 56.17, 56.61, 61.23, 122.76, 127.88, 128.44, 128.59, 129.29, 132.10, 132.65, 137.35, 138.33, 139.35, 141.74, 145.51, 156.93, 160.35, 162.80. ES-MS m/z 441 (M+H). Anal. Calcd. for C23H26N5O2Cl.0.2H2O: C, 62.28; H, 6.00; N, 15.79; Cl, 7.99. Found: C, 62.31; H, 5.83; N, 15.50; Cl, 8.06.

1. temperatureThe solution was then cooled
2. concentrationconcentrated under reduced pressure
3. customdried in vacuo
4. customThe crude material was purified by column chromatography with silica gel (50:1:0.1 CH2Cl2/MeOH/NH4OH)