反应详情

Sodium hydride (201.5 mg, 5.04 mmol) was added to a solution of N-[2-tert-butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]acetamide (549.8 mg, 1.68 mmol) (for preparation see in Example 9) in THF (50 mL) at 0° C. Stirring for 30 min., iodomethane was added. The resulting mixture was stirred overnight at room temperature and quenched with saturated NaHCO3 aqueous solution (5 mL) and water (10 mL). Two phases were separated. The aqueous was extracted with EtOAc (3×20 mL). The combined organic phases were washed with saturated NaHCO3 aqueous solution (20 mL), saturated NaCl aqueous solution (20 mL) and dried over Na2SO4. After evaporation of the solvent, the residue was purified by MPLC (EtOAc as eluent on silica gel) to give the desired title compound as a white solid (580.5 mg, 100%). 1H NMR (400 MHz, CD3OD): δ 1.26 (m, 5H), 1.67 (m, 2H), 1.69 (s, 9H), 1.71 (m, 1H), 1.78 (m, 2H), 1.87 (s, 3H), 2.14 (m, 1H), 3.30 (s, 3H), 4.49 (d, J=7.62 Hz, 2H), 7.55 (d, J=8.40 Hz, 1H), 7.71 (s, 1H), 8.00 (d, J=8.40 Hz, 1H). MS (ESI) (M+H)+: 342.3. Anal. Calcd for C21H31N3O+1.30 TFA+0.80H2O (504.14): C, 56.23; H, 6.78; N, 8.33. Found: C, 56.21; H, 6.77; N, 8.17.

1. stirringThe resulting mixture was stirred overnight at room temperature
2. customquenched with saturated NaHCO3 aqueous solution (5 mL) and water (10 mL)
3. customTwo phases were separated
4. extractionThe aqueous was extracted with EtOAc (3×20 mL)
5. washThe combined organic phases were washed with saturated NaHCO3 aqueous solution (20 mL), saturated NaCl aqueous solution (20 mL)
6. dry with materialdried over Na2SO4
7. customAfter evaporation of the solvent
8. customthe residue was purified by MPLC (EtOAc as eluent on silica gel)