反应详情

A solution of phenyl-(2-propyl-1H-benzoimidazol-5-yl)methanone (5.28 g; 0.02 mol) in DMF (80 mL) was stirred under an atmosphere of nitrogen. Sodium hydride (60% dispersion in oil, 0.8 g; 0.02 mol) was added. The mixture was then stirred for 0.5 hour at ambient temperature. 3,4-dichlorobenzyl bromide (4.8 g; 0.02 mol) was then added in portions. The mixture was stirred at 80-90° C. for 3.5 hours, then at ambient temperature for 18 hours. The solvent was evaporated under vacuum. The residue was extracted with ethyl acetate (300 mL) and washed with water (2×200 mL). The organic phase was evaporated. Purification was achieved by flash chromatography on silica gel (EtOAc/Hexane; 1:9 to 1:3). Recrystallization from ethyl acetate affords the tide compound (4.2 g; 50% yield) as a white solid, m.p. 168-169° C. Anal. Calcd. for C24H20Cl2N2O: C, 68.09; H, 4.76; N, 6.62. Found: C, 67.70; H, 4.46; N, 6.49. Mass spectrum (DEI; M+) m/z 422, 424, 426. 1H-NMR (DMSO -d6; 400 MHz) δ7.94 (d, 1H), 7.73 (d, 2H), 7.64-7.72 (m, 3H), 7.59 (m, 1H), 7.56 (t, 2H), 7.47 (d, 1H), 6.98 (dd, 1H), 5.59 (s, 2H), 2.84 (t, 2H), 1.76 (m, 2H) and 0.94 ppm (t, 3H).

1. stirringThe mixture was stirred at 80-90° C. for 3.5 hours
2. waitat ambient temperature for 18 hours
3. customThe solvent was evaporated under vacuum
4. extractionThe residue was extracted with ethyl acetate (300 mL)
5. washwashed with water (2×200 mL)
6. customThe organic phase was evaporated
7. customPurification
8. customRecrystallization from ethyl acetate
9. customaffords the tide compound (4.2 g; 50% yield) as a white solid, m.p. 168-169° C