反应详情

温度

55 °C

To a solution of 1-(4-chloro-benzyl)-piperazine (70 mg, 0.33 mmol) in THF (10 ml) was added 4-{3-[3-(4-fluoro-phenoxy)-propyl]-2-imino-2,3-dihydro-benzoimidazol-1-ylmethyl}-benzaldehyde, hydrobromide salt (0.20 g, 0.41 mmol), sodium cyanoborohydride (31 mg, 0.49 mmol), H2O (1 drop) and glacial acetic acid (0.068 ml). The reaction was warmed to 55° C. where it was maintained for 6 h. After this time, the mixture was cooled to rt and stirred for 16 h. The mixture was concentrated under reduced pressure and then partitioned between 1N HCl and EtOAc. The organic layer was removed and the aqueous phase was made basic using 10% K2CO3. The basic aqueous phase was extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by chromatography on silica eluting with MeOH/dichloromethane provided 1-{4-[4-(4-chloro-benzyl)-piperazin-1-ylmethyl]-benzyl}-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (23 mg, 11%). HPLC-MS 598 [M+1]+, 300.

1. temperaturewas maintained for 6 h
2. temperatureAfter this time, the mixture was cooled to rt
3. concentrationThe mixture was concentrated under reduced pressure
4. custompartitioned between 1N HCl and EtOAc
5. customThe organic layer was removed
6. extractionThe basic aqueous phase was extracted with EtOAc
7. dry with materialThe organic layer was dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customPurification by chromatography on silica eluting with MeOH/dichloromethane