N-bromobutanimide → 7-(4-Bromo-2-chlorophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one

HRID 1723687Notes

Reaction equation

HRID 1723687 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[C:10]([F:21])=[C:11]([F:20])[CH:12]=[C:13]2[C:17]=1[C:16](=[O:18])[NH:15][CH:14]2[CH3:19].C1C(=O)N([Br:29])C(=O)C1>CN(C=O)C.CCOC(C)=O>[Br:29][C:6]1[CH:5]=[CH:4][C:3]([NH:8][C:9]2[C:10]([F:21])=[C:11]([F:20])[CH:12]=[C:13]3[C:17]=2[C:16](=[O:18])[NH:15][CH:14]3[CH3:19])=[C:2]([Cl:1])[CH:7]=1

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 674048837-(2-Chlorophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one

Product 1

HCID 113612227-(4-Bromo-2-chlorophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-oneYield 47%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-f69f10249d1143a48b9ce1a10fa284b0
Source dataset
uspto-grants-2009_02
Patent number
US07485643B2

Reaction notes

Loading…