反应详情

温度

70 °C

To a warm (70° C.), stirred, solution of {3-[1-(4-Chloro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-(3,5-dimethyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine (0.141 g, 0.30 mmol) and DIPEA (0.32 mL, 1.84 mmol) in DMF (3 mL) was added imidazole-1-carboxylic acid (1H-imidazol-2-yl)-amide (2 equivs). After 1.5 hours, the mixture was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (30 mL) and washed with water (5×10 mL). The organic phase was dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) provided 157 mg (85%) of COMPOUND 275 as a white solid. 1H NMR (CDCl3) δ 1.28-1.39 (m, 2H), 1.58 (s, 6H), 1.65-1.71 (m, 2H), 2.24 (s, 3H), 2.29 (s, 3H), 2.56-2.65 (m, 3H), 3.36 (s, 2H), 3.68 (s, 2H), 4.10-4.14 (m, 2H), 6.68 (s, 2H), 6.83-6.85 (m, 2H), 7.07-7.10 (m, 2H), 7.17-7.21 (m, 2H), 7.81 (d, 1H, J=6.9 Hz), 8.09 (s, 1H), 8.50 (d, 1H, J=3.3 Hz); 13C NMR (CDCl3) δ 18.78, 19.21, 28.81, 31.76, 43.11, 45.08, 55.15, 55.65, 58.55, 122.21, 127.81, 129.21, 132.10, 132.30, 133.51, 134.67, 139.48, 143.61, 145.93, 147.15, 147.46, 149.05, 155.28, 156.16, 158.91; ES-MS m/z 572 (M+1) & 574 (M+1). Anal. Calcd. For C32H38N7OCl.0.4CH2Cl2: C, 64.20; H, 6.45; N, 16.18; Cl, 10.53. Found: C, 63.83; H, 6.43; N, 15.88; Cl, 10.92.

1. temperaturethe mixture was cooled to room temperature
2. concentrationconcentrated under reduced pressure
3. dissolutionThe residue was dissolved in CH2Cl2 (30 mL)
4. washwashed with water (5×10 mL)
5. dry with materialThe organic phase was dried (Na2SO4)
6. concentrationconcentrated
7. customPurification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH)