N-Iodosuccinimide → 7-(2-Chloro-4-iodophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one

HRID 1723686Notes

Reaction equation

HRID 1723686 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([I:29])C(=O)C1>C1COCC1.CO.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([I:29])[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]

Participants

5

Reactant 2

HCID 120273N-IodosuccinimideHCID 674048837-(2-Chlorophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one

Product 1

HCID 112819537-(2-Chloro-4-iodophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-oneYield 21.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of 7-(2-chlorophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one (18 mg, 0.059 mmol), NIS (17 mg, 0.074 mmol), and p-TsOH-H2O (24 mg, 0.12 mmol) in THF-MeOH (1 mL/1 mL) was stirred for 1 hour at room temperature. The reaction mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3 and water. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to give the crude material that was purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2) to afford 7-(2-chloro-4-iodophenylamino)-5,6-difluoro-3-methyl-2,3-dihydro-isoindol-1-one (5.4 mg, 21%). MS APCI (−) m/z 433, 435 (M-, Cl pattern) detected; 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 7.70 (d, 1H), 7.48 (dd, 1H), 6.75 (m, 2H), 6.04 (s, 1H), 4.63 (q, 1H), 1.49 (d, 3H).

Workup

  1. washwashed with saturated aqueous NaHCO3 and water
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give the crude material that
  6. customwas purified by silica gel flash column chromatography (100% CH2Cl2 to 1% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-aad316fcf0b14f9087ca943204224856
Source dataset
uspto-grants-2009_02
Patent number
US07485643B2

Reaction notes

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