反应详情

Combined 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (94 mg, 0.316 mmol), 7-Amino-1,5,5-trimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (67 mg, 0.307 mmol), 4 N HCl in dioxane (100 ul) and 2-methoxyethanol (4 mL). Heated reaction to 120° C. for 1.5 hours. Filtered off solid, then purified the solid with normal phase chromatography eluting with 97/3/1 CH2Cl2/MeOH/NH4OH to yield an off-white solid, 2-[5-Chloro-2-(1,5,5-trimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide (53 mg, 35%). LCMS: m/z=479.42 (M+H+), 1H NMR (400 MHz, CDCl3) δ 11.15 (s, 1H), 8.66 (d, 1H, J=8.3 Hz), 8.14 (d, 1H, J=1.3 Hz), 7.72 (dd, 1H, J=8.7, 2.1 Hz), 7.52 (d, 1H, J=7.8 Hz), 7.45 (m, 1H), 7.33 (s, 1H), 7.11 (m, 2H), 6.97 (s, 1H), 6.23 (br s, 1H), 3.31 (s, 3H), 3.06 (d, 3H, J=4.8 Hz), 2.33 (m, 2H), 2.05 (m, 2H), 1.31 (s, 6H).

1. temperatureHeated
2. customreaction to 120° C. for 1.5 hours
3. filtrationFiltered off solid
4. custompurified the solid with normal phase chromatography
5. washeluting with 97/3/1 CH2Cl2/MeOH/NH4OH