Water → 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-(5-methylhexylamino)-4H-1-benzopyran-4-one

HRID 1736212Notes

Reaction equation

HRID 1736212 reaction equation
[NH2:1][C:2]1[C:7]2[C:8](=[O:26])[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[C:14]([F:25])[CH:13]=3)[O:11][C:6]=2[C:5]([F:27])=[CH:4][C:3]=1[F:28].Br[CH2:30][CH2:31][CH2:32][CH2:33][CH:34]([CH3:36])[CH3:35].[H-].[Na+].O>CN(C)C=O>[F:28][C:3]1[CH:4]=[C:5]([F:27])[C:6]2[O:11][C:10]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[C:14]([F:25])[CH:13]=3)=[CH:9][C:8](=[O:26])[C:7]=2[C:2]=1[NH:1][CH2:30][CH2:31][CH2:32][CH2:33][CH:34]([CH3:36])[CH3:35]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 5207261-Bromo-5-methylhexaneHCID 194349345-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one

Product 1

HCID 194348276,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-(5-methylhexylamino)-4H-1-benzopyran-4-oneYield 71.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

853 mg (2.19mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-1-benzopyran-4-one obtained in Example 66 was dissolved in 20 mL of dimethylformamide under argon atmosphere, 788 mg (4.38 mmol) of 1-bromo-5-methylhexane and 266 mg (6.65mmol) of sodium hydride (60% oil dispersion) were added under ice-cooling and the mixture was stirred at room temperature for 5.5 hours. The reaction solution was cooled on ice, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (chloroform: n-hexane=3:1) to give 762 mg of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-(5-methylhexylamino)-4H-1-benzopyran-4-one (yield: 71%).

Workup

  1. temperaturecooling
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (chloroform: n-hexane=3:1)

Sources & evidence

ORD record
ord-69a013f8d82f41d1bffffc74ddd6cff9
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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