反应详情

温度

70 °C

To a stirred suspension of 4-hydroxy-N,N,1,2-tetramethyl-1H-benzimidazole-6-carboxamide (50 mg, 0.21 mmol, WO 2004054984) in N,N-dimethylformamide (2 mL) was added sodium hydride (60% dispersion in mineral oil, 11 mg, 0.27 mmol) at room temperature. After stirring for 20 minutes, a solution of 4-chlorochromane (71 mg, 0.42 mmol, WO 2000078751) in N,N-dimethylformamide (1 mL) was added at room temperature. The reaction mixture was warmed to 70° C., and stirred for 6 hours at the same temperature. The reaction mixture was quenched with sodium hydrogencarbonate aqueous solution, and extracted with ethyl acetate (20 mL×2). The combined extracts were washed with water and brine, dried over magnesium sulfate, and concentrated in vacuum. The residue was purified by column chromatography on silica gel (ethyl acetate:methanol=10:1 as an eluent) to afford the title compound as a white solid (40 mg, 52%):

1. stirringstirred for 6 hours at the same temperature
2. customThe reaction mixture was quenched with sodium hydrogencarbonate aqueous solution
3. extractionextracted with ethyl acetate (20 mL×2)
4. washThe combined extracts were washed with water and brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated in vacuum
7. customThe residue was purified by column chromatography on silica gel (ethyl acetate