反应详情

温度

130 °C

Combined 8-Methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (55 mg, 0.00022 mol), (2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine (86 mg, 0.00024 mol), 4 M of Hydrogen chloride in 1,4-Dioxane (70 uL) and Isopropyl alcohol (2.2 mL, 0.029 mol;) in microwave vessel. Heat at 130° C. for 10 minutes. Heat for another 10 minutes. Cool to room temp. Solid precipitated out of solution. Filtered off solid. The filtrate was treated with MP-carbonate 250 mgs and stirred for 30 min. The mixture was concentrated and purified by ISCO chromatography (40 g SiO2 column, gradient 100% DCM to 10% MeOH/DCM. Isolated 5-Chloro-N*2*-[8-methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-pyrimidine-2,4-diamine as an off-white solid (49 mgs, 39%) Melting point: 138-140° C. δ 8.30 (d, J=8.8 Hz, 1H), 8.12 (s, 1H), 8.03 (d, J=1.8 Hz, 1H), 7.57 (s, 1H), 7.45 (s, 1H), 6.65 (s, 1H), 6.57-6.52 (m, 2H), 3.94-3.88 (m, 10H), 3.36 (br s, 2H), 3.39 (d, J=1.7 Hz, 3H), 3.18-3.17 (m, 4H), 2.90-2.74 (m, 10H); LC/MS: 568.87 (M+H).

1. temperatureHeat for another 10 minutes
2. temperatureCool to room temp
3. customSolid precipitated out of solution
4. filtrationFiltered off solid
5. additionThe filtrate was treated with MP-carbonate 250 mgs
6. concentrationThe mixture was concentrated
7. custompurified by ISCO chromatography (40 g SiO2 column, gradient 100% DCM to 10% MeOH/DCM