反应详情

A solution of 2-(3-{[2,2-difluoro-2-(4-fluoronaphthyl)ethyl]amino}-6-chloro-2-fluorophenyl)-N-({6-[(tert-butoxy)carbonylamino]-2-methyl(3-pyridyl)}methyl)acetamide (10 mg, 16 μmol), as prepared in the preceding step, in HCl (0.5 mL, 4.0 M in 1,4-dioxane) was stirred for 2 hours at ambient temperature. A solution of MeOH/DCM (25%, 0.4 mL) was added, and the mixture continued to stir overnight. The solvents were evaporated, and the resulting brown residue was flash chromatographed on silica gel eluting with MeOH/DCM (2.5, 5, and 10%) to give a solid product. It was treated with HCl solution (0.01 mL, 4.0 M in 1,4-dioxane, 40 μmol) in DCM (0.5 mL), stirred for 5 minutes, and the solvents evaporated to give the title compound (6.2 mg, 69% yield) as a white solid. 1H-NMR (400 MHz, CD3OD) δ 8.26 (d, J=8.4 Hz, 1H), 8.17-8.14 (m, 1H), 7.80 (d, J=9.1 Hz, 1H), 7.73-7.64 (m, 4H), 7.20 (dd, J=10.0, 8.3 Hz, 1H), 6.82-6.79 (m, 1H), 6.49 (t, J=9.1 Hz, 1H), 4.24 (s, 2H), 4.10-4.02 (m, 2H), 3.66 (d, J=2.3 Hz, 2H), 2.49 (s, 3H). Mass spectrum (LCMS, ESI) calc'd for C27H24ClF4N4O (M+H): 531.1. Found: 531.6.

1. stirringto stir overnight
2. customThe solvents were evaporated
3. customchromatographed on silica gel eluting with MeOH/DCM (2.5, 5, and 10%)
4. customto give a solid product
5. stirringstirred for 5 minutes
6. customthe solvents evaporated