反应详情

Combined N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (114 mg, 0.336 mmol), 7-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (80 mg, 0.344 mmol), 4 N HCl in dioxane (103 ul) and 2-methoxyethanol (5 mL). Heated reaction to 120° C. for 2.5 hours. Evaporated off solvent and purified with normal phase chromatography to yield a white solid, N-{(1R,2R)-2-[5-Chloro-2-(1-ethyl-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide (69 mg, 38%). LCMS: m/z=535.34 (M+H+), 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.65 (dd, 1H, J=8.6, 1.3 Hz), 7.36 (d, 1H, J=2.3 Hz), 7.21 (d, 1H, J=8.6 Hz), 6.91 (s, 1H), 5.44 (d, 1H, J=7.6 Hz), 5.36 (d, 1H, J=6.8 Hz), 3.87 (m, 3H), 3.24 (m, 1H), 2.82 (s, 3H), 2.17 (m, 6H), 1.84 (m, 2H), 1.37 (m, 13H).

1. temperatureHeated
2. customreaction to 120° C. for 2.5 hours
3. customEvaporated off solvent
4. custompurified with normal phase chromatography