反应详情

温度

150 °C

A mixture of 4-((4-fluorobenzyl)oxy)pyridin-2(1H)-one (2.44 g), 6-bromo-2-cyclopropyl-1-methyl-1H-benzimidazole (2.8 g), potassium carbonate (4.62 g), N,N′-dimethylethylenediamine (1.20 ml), copper iodide (2.12 g) and DMSO (56 ml) was stirred at 150° C. under Ar atmosphere for 2 h. After cooling to 0° C., 28% NH3 solution (56.0 ml) was added. The mixture was stirred at 0° C. for 1 h and then at room temperature for 1 h. The precipitate was collected by filtration and washed with water and IPE. The collected material was dissolved in THF (500 ml), passed through a short NH silica gel column (EtOAc 100%) and concentrated in vacuo. The resulting solid was collected, washed with IPE (50 ml) and then EtOAc (50 ml), and dissolved in MeOH. To the solution was added activated carbon (ca. 200 mg), and the mixture was stirred at room temperature for 10 min. The insoluble material was removed by filtration and the filtrate was concentrated in vacuo. The residue was purified by NH silica gel column chromatography (hexane/EtOAc), and recrystallized from EtOH/water to give the title compound (1.60 g) as an off-white solid.

1. temperatureAfter cooling to 0° C.
2. stirringThe mixture was stirred at 0° C. for 1 h
3. waitat room temperature for 1 h
4. filtrationThe precipitate was collected by filtration
5. washwashed with water and IPE
6. dissolutionThe collected material was dissolved in THF (500 ml)
7. concentrationconcentrated in vacuo
8. customThe resulting solid was collected
9. washwashed with IPE (50 ml)
10. dissolutionEtOAc (50 ml), and dissolved in MeOH
11. additionTo the solution was added activated carbon (ca. 200 mg)
12. stirringthe mixture was stirred at room temperature for 10 min
13. customThe insoluble material was removed by filtration
14. concentrationthe filtrate was concentrated in vacuo
15. customThe residue was purified by NH silica gel column chromatography (hexane/EtOAc)
16. customrecrystallized from EtOH/water