反应详情

温度

110 °C

2-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (100 mg, 0.4 mmol), and 7-Amino-1-ethyl-8-methoxy-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (104 mg, 0.444 mmol), 4 M of Hydrogen chloride in 1,4-Dioxane (100 uL), 2-Methoxyethanol (4.5 mL, 57 mmol) were charged into Radley tube. Heat 110° C. for about 3 hours, cooled to room temperature. The mixture was treated with excess MP-carbonate and stirred 30 min. Filtration followed by concentration gave a yellow film. Treatment with EtOAc and sonication provided an off-white solid. This material was stripped onto Celite and purified on ISCO column (40 g SiO2, gradient 50% EtOAc hexane to 100% EtOAc to 5% MeOH/EtOAc) gave 2-[5-Chloro-2-(1-ethyl-8-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide as a white solid (42.06 mg, 20%). MP: 232-233° C. 1H-NMR (dmso, 400 MHz) δ 11.56 (s, 1H), 8.74 (d, J=4.5 Hz, 1H), 8.53 (d, J=8.5 Hz, 1H), 8.23 (s, 1H), 8.20 (s, 1H), 7.73 (d J=7.8 Hz, 1H), 7.67 (s, 1H), 7.32 (t, J=7.8 Hz, 1H), 7.11 (t, J=7.6 Hz, 1H), 7.05 (s, 1H) 3.85-3.80 (broad m, 2H), 3.83 (s, 3H), 2.80 (d, J=4.2 Hz, 3H), 2.50-2.49 (m, 2H), 2.12-2.10 (m, 2H), 2.10-1.99 (m, 2H), 1.01 (t, J=7.0 Hz, 3H); LC/MS: 495.37 (M+H).

1. temperaturecooled to room temperature
2. filtrationFiltration
3. concentrationfollowed by concentration
4. customgave a yellow film
5. customprovided an off-white solid
6. custompurified on ISCO column (40 g SiO2, gradient 50% EtOAc hexane to 100% EtOAc to 5% MeOH/EtOAc)