反应详情

To a cooled (0° C.) solution of [2-(3-cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-1-(3-methyl-butyl)-1H-benzoimidazol-5-ylmethyl]-carbamic acid tert-butyl ester (34 mg, 0.064 mmol) and anisole (70 μL, 0.64 mmol) in DCM (2 mL) was added TFA (148 μL, 1.92 mmol). The solution was allowed to reach room temperature and concentrated after 4 h. The residue was stripped with DCM (2×) and methanol (1×). The TFA salt was dissolved in methanol followed by the addition of acetyl cloride (46 μL, 0.64 mmol). After 10 min the solution was concentrated in vacuo and stripped with methanol (2×) and dichloromethane (2×) to give 1-[5-aminomethyl-1-(3-methyl-butyl)-1H-benzoimidazol-2-ylmethyl]-3-cyclopropyl-1H-quinazoline-2,4-dione; HCl salt (24 mg, 80%) as an off white solid.

1. customto reach room temperature
2. concentrationconcentrated after 4 h
3. dissolutionThe TFA salt was dissolved in methanol
4. concentrationAfter 10 min the solution was concentrated in vacuo