反应详情

A flask containing 1-(4-bromophenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide (EXAMPLE C2, 100 mg, 0.25 mmol) and 3-phenoxypropylamine hydrochloride (54 mg, 0.29 mmol) was evacuated and refilled with N2 (2×). To this was added BINAP (112 mg, 0.18 mmol), Pd2 dba3 (55 mg, 0.06 mmol) and t-BuONa (68 mg, 0.7 mmol) in one portion as a mixture, with minimum exposure to air. The flask was again evacuated and refilled with N2 (3×). Degassed, anhydrous dioxane (2 mL) was added via syringe and the solution was stirred under N2 for 10 min at rt and then at 80° C. for 18 h. Later, the reaction was cooled to rt, filtered through Celite (using MeOH and CH2Cl2 to rinse the Celite), concentrated under reduced pressure and purified using the Waters mass-directed HPLC purification system to provide 1-{4-[(3-phenoxypropyl)amino]phenyl}-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide as a white solid. MS (ES+): m/z 478 (100) [MH+].

1. customwas evacuated
2. additionrefilled with N2 (2×)
3. customThe flask was again evacuated
4. additionrefilled with N2 (3×)
5. customDegassed
6. additionanhydrous dioxane (2 mL) was added via syringe
7. waitat 80° C. for 18 h
8. temperatureLater, the reaction was cooled to rt
9. filtrationfiltered through Celite (
10. washto rinse the Celite),
11. concentrationconcentrated under reduced pressure
12. custompurified
13. customthe Waters mass-directed HPLC purification system