反应详情

温度

120 °C

7-Amino-8-methoxy-1,3,4,5-tetrahydro-benzo[d]azepin-2-one (50 mg, 0.2 mmol), N-[(1R,2R)-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (90.5 mg, 0.27 mmol), and a 4 M solution of hydrogen chloride in dioxane (0.1 mL, 2 eq), were added to 2-methoxyethanol (2 mL), and the reaction mixture was heated for 6 hours at 120° C. The reaction mixture was partitioned between aqueous saturated Na2CO3 and dichloromethane, and the aqueous phase was extracted twice with dichloromethane. The combined organic extracts were dried (MgSO4), filtered, and then concentrated on SiO2. Flash chromatography on SiO2 (MeOH/dichloromethane 0-5%) gave N-{(1R,2R)-2-[5-Chloro-2-(8-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide (47 mg, 30%) as a beige solid. MP: 109-115° C.; 1H-NMR (CDCl3) δ 8.06 (s, 1H), 7.90 (s, 1H), 7.40 (s, 1H), 6.62 (s, 1H), 6.18 (m, 1H), 6.00 (d, J=6.5 Hz, 1H), 5.51 (d, J=7.8 Hz, 1H), 3.94 (m, 1H), 3.86 (s, 3H), 3.75 (m, 2H), 3.53 (m, 2H), 3.25 (m, 1H), 3.04 (t, J=6.1 Hz, 2H), 2.85 (s, 3H), 2.60 (s, 2H), 2.20 (m, 2H), 1.8 (m, 2H), 1.34 (m, 2H); LC/MS (ESI+): 509.28 (M+H).

1. customThe reaction mixture was partitioned between aqueous saturated Na2CO3 and dichloromethane
2. extractionthe aqueous phase was extracted twice with dichloromethane
3. dry with materialThe combined organic extracts were dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated on SiO2