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

HRID 1736208Notes

Reaction equation

HRID 1736208 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][Cl:34].[H-].[Na+].O>CN(C)C=O>[Cl:34][CH2:33][CH2:32][CH2:31][CH2:30][NH: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]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 813641-Bromo-4-chlorobutaneHCID 194349345-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one

Product 1

HCID 194349485-(4-chlorobutylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-oneYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.52 g (3.90 mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one obtained in Example 66 was dissolved in 30 mL of dimethylformamide under argon atmosphere, 2.25 mL (19.5 mmol) of 1-bromo-4-chlorobutane and 470 mg (11.8 mmol) of sodium hydride (60% oil dispersion) were added under ice-cooling and the mixture was stirred at room temperature for 1.3 hours. The reaction solution was cooled on ice, water was added and the mixture was extracted three times 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:ethyl acetate=100:1) to give 1.06 g of 5-(4-chlorobutylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one (yield: 57%).

Workup

  1. temperaturecooling
  2. additionwas added
  3. extractionthe mixture was extracted three times 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:ethyl acetate=100:1)

Sources & evidence

ORD record
ord-d491c21e139c45a0ab4e1725ed12fc52
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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