反应详情

温度

135 °C

A suspension of 4-(4-chlorobenzyloxy)pyridin-2(1H)-one (91.0 mg, 0.38 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H) carboxylate (160 mg, 0.42 mmol), 8-hydroxyquinoline (11 mg, 0.072 mmol) and Cs2CO3 (137 mg, 0.42 mmol) in DMSO (10.0 mL) was degassed under reduced pressure for 40 min. CuI (87 mg, 0.46 mmol) was added to the above solution, and the reaction mixture was degassed under reduced pressure for 2×5 min. The reaction mixture was heated at 135° C. under nitrogen overnight. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added, and the resulting suspension was stirred at 25° C. for 5 min. Celite was added, and the suspension was stirred for 5 min. The suspension was filtered through Celite, and the filtrate was washed with brine. The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. The residue was dissolved in dichloromethane (1.0 mL), and HCl (2M in diethyl ether, 5.0 mL) was added. The resulting slurry was stirred at room temperature overnight and concentrated under reduced pressure. Purification by preparative HPLC followed by preparative TLC (DCM/MeOH/concentrated ammonia 96:3.6:0.4) and preparative HPCL afforded the title compound (41 mg, 23%) as a white solid: 1H NMR (500 MHz, CD3OD) δ 7.58 (d, J=8.5 Hz, 1H), 7.57 (d, J=7.5 Hz, 1H), 7.47 (d, J=8.5 Hz, 2H), 7.43 (d, J=8.5 Hz, 2H), 7.39 (d, J=1.5 Hz, 1H), 7.01 (dd, J=8.5, 2.0 Hz, 1H), 6.28 (dd, J=8.0, 3.0 Hz, 1H), 6.11 (d, J=2.5 Hz, 1H), 5.17 (s, 2H), 3.74 (s, 3H), 3.54 (t, J=5.5 Hz, 2H), 3.48 (t, J=5.5 Hz, 2H), 3.35-3.33 (m, 2H), 3.23 (t, J=5.5 Hz, 2H); ESI MS m/z 434 [M+H]+.

1. customwas degassed under reduced pressure for 40 min
2. customthe reaction mixture was degassed under reduced pressure for 2×5 min
3. temperatureThe suspension was cooled
4. addition9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added
5. additionCelite was added
6. stirringthe suspension was stirred for 5 min
7. filtrationThe suspension was filtered through Celite
8. washthe filtrate was washed with brine
9. dry with materialThe resulting solution was dried over Na2SO4
10. concentrationconcentrated under reduced pressure
11. dissolutionThe residue was dissolved in dichloromethane (1.0 mL)
12. additionHCl (2M in diethyl ether, 5.0 mL) was added
13. stirringThe resulting slurry was stirred at room temperature overnight
14. concentrationconcentrated under reduced pressure
15. customPurification by preparative HPLC