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

HRID 1736217Notes

Reaction equation

HRID 1736217 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:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]Br.[H-].[Na+].O>CN(C)C=O>[Br:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][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 81001,5-DibromopentaneHCID 24758Sodium hydrideHCID 194349345-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one

Product 1

HCID 194348655-(5-bromopentylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-oneYield 59.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2.05 g (5.26mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one obtained in Example 66 was dissolved in 50 mL of dimethylformamide under argon atmosphere, 3.6 mL (26.3 mmol) of 1,5-dibromopentane and 631 mg (15.8 mmol) of sodium hydride (60% oil dispersion) were added and the mixture was stirred at room temperature for 1.2 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:ethyl acetate=60:l) to give 1.68 g of 5-(5-bromopentylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one (yield: 59%).

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (chloroform:ethyl acetate=60:l)

Sources & evidence

ORD record
ord-0a93483f783e404ca55e29510deda4dc
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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