反应详情

温度

120 °C

5-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (100 mg, 0.2 mmol), 2-(methyloxy)-4-[1-(2-methylpropyl)-4-piperidinyl]aniline (Example 160, step C) (47 mg, 0.18 mmol), and p-toluenesulfonic acid (90 mg, 0.47 mmol) were weighed into a 20 mL vial. 7 mL of iPrOH was added and the mixture was heated to 120° C. for 48 h. The mixture was transferred to a 50 mL round bottom and neutralized with 3 mL of 0.5 N sodium methoxide. The solvent was rotovaped down. The residue was taken up in 10 mL of DCM. 1 g of silica gel was added. The solvent was rotovaped down and the pre-adsorbed solids were purified by flash chromatography to give the title compound (67 mg, 0.092 mmol, 52%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.73 (s, 1H), 9.37 (d, J=6.78 Hz, 1H), 8.50 (s, 1H), 8.24 (d, J=5.31 Hz, 1H), 8.04 (d, J=2.01 Hz, 1H), 7.67-7.75 (m, 2H), 7.64 (d, J=8.06 Hz, 1H), 7.41-7.46 (m, 1H), 7.32-7.40 (m, 1H), 7.25 (d, J=8.79 Hz, 1H), 7.17 (t, J=8.15 Hz, 2H), 6.94-6.98 (m, 2H), 6.78 (dd, J=8.24, 1.46 Hz, 1H), 6.59 (d, J=5.31 Hz, 1H), 4.25 (q, J=6.84 Hz, 2H), 3.82 (s, 3H), 2.90 (d, J=10.44 Hz, 2H), 2.42-2.46 (m, 1H), 2.02 (d, J=7.14 Hz, 2H), 1.91 (t, J=10.44 Hz, 2H), 1.65-1.75 (m, 5H), 1.41 (t, J=6.87 Hz, 3H), 0.84 (d, J=6.41 Hz, 6H). MS (ESI): 732 [M+H]+.

1. addition1 g of silica gel was added
2. customthe pre-adsorbed solids were purified by flash chromatography