反应详情

Combined 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (82 mg, 0.276 mmol), 7-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (61 mg, 0.263 mmol), 4 N HCl in dioxane (80 ul) and 2-methoxyethanol (3 mL). Heated reaction to 120° C. for 3.5 hours. Filtered off solid, then purified the solid with normal phase chromatography eluting with 9/1 methylene chloride/methanol. Washed product with saturated sodium bicarbonate solution and extracted into methylene chloride. Washed organic phase with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield an off-white solid, 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]-N-methyl-benzamide (34 mg, 25%). LCMS: m/z=493.37 (M+H+), 1H NMR (400 MHz, CDCl3) δ 11.11 (s, 1H), 8.60 (d, 1H, J=8.3 Hz), 8.09 (s, 1H), 7.68 (dd, 1H, J=8.3, 2.3 Hz), 7.52 (d, 1H, J=7.3 Hz), 7.39 (m, 1H), 7.33 (d, 1H, J=2.3 Hz), 7.16 (d, 1H, J=8.8 Hz), 7.08 (m, 1H), 6.70 (br s, 1H), 3.79 (m, 2H), 3.40 (s, 1H), 3.01 (d, 3H, J=4.5 Hz), 2.38 (s, 2H), 2.27 (m, 2H), 1.29 (m, 9H).

1. temperatureHeated
2. customreaction to 120° C. for 3.5 hours
3. filtrationFiltered off solid
4. custompurified the solid with normal phase chromatography
5. washeluting with 9/1 methylene chloride/methanol
6. extractionWashed product with saturated sodium bicarbonate solution and extracted into methylene chloride
7. dry with materialWashed organic phase with brine, dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure