反应详情

温度

120 °C

7-Amino-1,2,4,5-tetrahydro-benzo[d]azepin-3-carboxylic acid dimethylamide (80 mg, 0.343 mmol, 1.0 eq) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (112 mg, 0.378 mmol, 1.1 eq) were dissolved in IPA (3 mL). 4.0 M HCl in dioxane (94.5 μL, 0.378 mmol, 1.1 eq) was added and the reaction was heated at 120° C. in a microwave for 10 minutes. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (20 mL) and washed with sat. NaHCO3 (20 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-10% MeOH/CH2Cl2 as the eluting solvent to obtain 7-[5-chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid dimethylamide as a yellow foam (137 mg, 81%). LCMS (m/e) 494 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 11.08 (s, 1H), 8.66 (d, 1H, J=8.4 Hz), 8.11 (s, 1H), 7.51 (d, 1H, J=7.8 Hz), 7.50-7.40 (m, 1H), 7.40 (s, 1H), 7.30-7.25 (m, 1H), 7.14-7.02 (m, 2H), 6.93 (s, 1H), 6.32-6.21 (m, 1H), 3.46-3.38 (m, 4H), 3.05 (d, 3H, J=4.8 Hz), 2.98-2.90 (m, 4H), 2.87 (s, 3H), 2.86 (s, 3H).

1. concentrationThe reaction was then concentrated under reduced pressure
2. washwashed with sat. NaHCO3 (20 mL)
3. dry with materialThe organic layer was dried (sodium sulfate)
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customPurification by basic alumina chromatography