反应详情

A solution of N-[3-(3,4-diamino-phenoxy)-phenyl]-acetamide (Step B, 320 mg, 1.2 mmol, 1.0 eq.) in 20 mL of anhydrous CH3CN was added drop-wise to a solution of 1-(2-chloro-5-isothiocyanato-benzyl)-4-methyl-piperazine (300 mg, 1.2 mmol, 1.0 eq.) in 10 mL of CH3CN. The reaction was stirred for 2 h at RT. EDC (360 mg, 1.9 mmol, 1.5 eq.) was added and the reaction was heated to 80° C. and stirred for 1 h. The mixture was cooled and concentrated. The residue was dissolved into EtOAc and washed with H2O and sat. NaHCO3 (aq.). The organic layer was dried (MgSO4), filtered and concentrated. The crude was further purified by column chromatography (0-10% MeOH/CH2Cl2 with 1% NH4OH) followed by recrystallization from CH2Cl2 to give pure N-(3-{2-[4-chloro-3-(4-methyl-piperazin-1-ylmethyl)-phenylamino]-1H-benzimidazol-5-yloxy}-phenyl)-acetamide. MS m/z=506.2 (M+H)+; Calc'd for C27H29N6O2: 504.20.

1. temperaturethe reaction was heated to 80° C.
2. stirringstirred for 1 h
3. temperatureThe mixture was cooled
4. concentrationconcentrated
5. dissolutionThe residue was dissolved into EtOAc
6. washwashed with H2O and sat. NaHCO3 (aq.)
7. dry with materialThe organic layer was dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude was further purified by column chromatography (0-10% MeOH/CH2Cl2 with 1% NH4OH)
11. customfollowed by recrystallization from CH2Cl2