反应详情

温度

135 °C

A suspension of 4-(2,4-difluorobenzyloxy)pyridin-2(1H)-one (116 mg, 0.487 mmol), tert-butyl 2-bromo-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridine-6-carboxylate (196 mg, 0.536 mmol), CuI (111 mg, 0.584 mmol), 8-hydroxyquinoline (14 mg, 0.097 mmol) and Cs2CO3 (175 mg, 0.536 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under N2 and stirred at 135° C. for 20 h. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH was added, and the resulting suspension was stirred at 25° C. for 30 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine. Activated carbon was added to the solution, and the resulting suspension was filtered. The filtrate was dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography on silica gel (Et2O/(8:1.9:0.1 Et2O/MeOH/NH4OH)) afforded a clear wax. 2 N HCl in Et2O (100 mL) was added to a solution of the clear wax in CH2Cl2 (10 mL) under N2, and the resulting suspension was stirred at 25° C. overnight. The suspension was filtered under N2, and the solid was washed with Et2O. The solid was put in a vacuum oven at 40° C. for 16 h to afford 119 mg (58%) of the title compound as a white solid: mp 206-210° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.28 (s, 2H), 8.07 (d, J=8.5 Hz, 1H), 7.82 (d, J=7.5 Hz, 1H), 7.67 (dd, J=15.0, 8.5 Hz, 1H), 7.40-7.33 (m, 2H), 7.18 (ddd, J=8.5, 8.5, 2.0 Hz, 1H), 6.15 (dd, J=8.5, 2.5 Hz, 1H), 6.07 (d, J=2.5 Hz, 1H), 5.17 (s, 2H), 4.37 (br s, 2H), 3.72 (s, 3H), 3.58-3.52 (m, 2H), 3.14 (t, J=5.5 Hz, 2H); ESI MS m/z 423 [M+H]+.

1. customwas degassed under reduced pressure for 45 min
2. temperatureThe suspension was cooled
3. addition9:0.9:0.1 CH2Cl2/MeOH/NH4OH was added
4. stirringthe resulting suspension was stirred at 25° C. for 30 min
5. washthe filtrate was washed with brine
6. additionActivated carbon was added to the solution
7. filtrationthe resulting suspension was filtered
8. dry with materialThe filtrate was dried over Na2SO4
9. concentrationconcentrated under reduced pressure
10. customFlash chromatography on silica gel (Et2O/(8:1.9:0.1 Et2O/MeOH/NH4OH)) afforded a clear wax
11. stirringthe resulting suspension was stirred at 25° C. overnight
12. filtrationThe suspension was filtered under N2
13. washthe solid was washed with Et2O
14. waitThe solid was put in a vacuum oven at 40° C. for 16 h