反应详情

温度

120 °C

A microwave vessel was charged with 8-amino-1-ethyl-1,3,4,5-tetrahydro-1-benzazepin-2-one (44.7 mg, 0.219 mmol), 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3,N-dimethyl-benzamide (56.8 mg, 0.182 mmol) 10-camphorsulfonic acid (4.2 mg, 0.018 mmol) and isopropyl alcohol (2.0 mL) and heated in a microwave at 120° C. for 60 minutes. The reaction mixture was quenched with a slurry of saturated, aqueous, NaHCO3 and stirred for 2 h. This mixture was diluted with water (10 mL) and extracted into DCM. The organic layer was dried by passing through a funnel filled with Na2SO4, and the filtrate was evaporated onto celite prior to purification by chromatography (amine modified silica gel, 25% EtOAc/hexane→80% EtOAc gradient). The appropriate fractions were combined, evaporated to afford a solid that was triturated with ether (2×2 mL) and yielded product (49.5 mg, 57%) as a white powder that had the following properties: m.p: 210-212° C.; LC/MS (ESI+): 479 (M+H); 1H-NMR (DMSO-d6, 400 MHz): δ 9.29-9.20 (m, 2H), 8.30 (m, 1H), 8.14 (s, 1H), 7.48-7.40 (m, 2H), 7.36 (d, J=8.3, 1H), 7.29-7.20 (m, 2H), 6.93 (d, J=8.3, 1H), 3.55 (br s, 2H), 2.70 (d, J=4.1, 3H), 2.50 (m, 2H), 2.15 (s, 3H), 2.10-1.85 (m, 4H), 0.92 (t, J=7.0, 3H).

1. customThe reaction mixture was quenched with a slurry of saturated, aqueous, NaHCO3
2. additionThis mixture was diluted with water (10 mL)
3. extractionextracted into DCM
4. customThe organic layer was dried
5. customby passing through a funnel
6. additionfilled with Na2SO4
7. customthe filtrate was evaporated onto celite
8. customto purification by chromatography (amine modified silica gel, 25% EtOAc/hexane→80% EtOAc gradient)
9. customevaporated
10. customto afford a solid
11. customthat was triturated with ether (2×2 mL)