Reacción #497531

Ecuación de reacción

1-(4-chloro-benzyl)-piperazine

4-{3-[3-(4-fluoro-phenoxy)-propyl]-2-imino-2,3-dihydro-benzoimidazol-1-ylmethyl}-benzaldehyde, hydrobromide salt

sodium cyanoborohydride

acetic acid

→

1-{4-[4-(4-chloro-benzyl)-piperazin-1-ylmethyl]-benzyl}-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine

Rendimiento 11.7%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawas maintained for 6 h
2. 2
   TemperaturaAfter this time, the mixture was cooled to rt
3. 3
   ConcentraciónThe mixture was concentrated under reduced pressure
4. 4
   Otropartitioned between 1N HCl and EtOAc
5. 5
   OtroThe organic layer was removed
6. 6
   ExtracciónThe basic aqueous phase was extracted with EtOAc
7. 7
   SecadoThe organic layer was dried (Na2SO4)
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated under reduced pressure
10. 10
    OtroPurification by chromatography on silica eluting with MeOH/dichloromethane

Procedimiento

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.

Fuente