反应详情

A mixture of 7-(2-chlorophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one (68 mg, 0.22 mmol, prepared by the procedures described in Example 1) and NBS (46 mg, 0.26 mmol) in DMF (2 mL) was stirred for 3 hours at room temperature. The reaction mixture was diluted with EtOAc and washed with water. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to give the crude material which was purified by silica gel flash column chromatography (100% hexanes to 25% EtOAc in hexanes) to afford 7-(4-bromo-2-chlorophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one (40 mg, 47%). MS APCI (−) m/z 385, 387 (M-, Br, Cl pattern) detected; 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 7.54 (d, 1H), 7.31 (dd, 1H), 6.89 (t, 1H), 6.75 (dd, 1H), 6.05 (s, 1H), 4.63 (q, 1H), 1.49 (d, 3H).

1. customprepared by the procedures
2. washwashed with water
3. dry with materialThe organic layer was dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto give the crude material which
7. customwas purified by silica gel flash column chromatography (100% hexanes to 25% EtOAc in hexanes)