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]-methyl-carbamic acid tert-butyl ester (39 mg, 0.071 mmol) and anisole (77 μL, 0.71 mmol) in DCM (3 mL) was added TFA (165 μL, 2.14 mmol). The solution was allowed to reach room temperature and after 1 h another amount of TFA (200 μL) was added. After 1 h the volatiles were removed in vacuo and the residue was stripped with DCM (2×) and methanol (1×). The TFA salt was dissolved in methanol followed by the addition of acetyl cloride (50 μL, 0.71 mmol) and concentrated. This procedure was repeated once. The product was triturated in diethyl ether to give 3-cyclopropyl-1-[5-methylaminomethyl-1-(3-methyl-butyl)-1H-benzoimidazol-2-ylmethyl]-1H-quinazoline-2,4-dione; HCl salt (31 mg, 91%) as an off white solid.

1. customAfter 1 h the volatiles were removed in vacuo
2. dissolutionThe TFA salt was dissolved in methanol
3. concentrationconcentrated
4. customThe product was triturated in diethyl ether