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

HRID 1736144Notes

Reaction equation

HRID 1736144 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].[H-].[Na+].Br[CH2:32][CH2:33][CH2:34][CH2:35][Cl:36].O>CN(C)C=O>[Cl:36][CH2:35][CH2:34][CH2:33][CH2:32][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 hydride2×HCID 813641-Bromo-4-chlorobutane2×HCID 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 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.01 g (2.59 mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one obtained in Example 66 was dissolved in 20 ml of dimethylformamide under argon atmosphere, 228 mg of sodium hydride (60% oil dispersion) and 1.5 ml of 1-bromo-4-chlorobutane were added under ice-cooling and the mixture was stirred at room temperature for 3 hours. 228 mg of sodium hydride (60% oil dispersion) and 1.5 ml of 1-bromo-4-chlorobutane were further added and the mixture was stirred for additional 1 hour. Water was added to the reaction solution and the mixture was extracted three times with ethyl acetate. The organic layer was washed twice with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1) to give 396 mg (32%) of 5-(4-chlorobutylamino)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for additional 1 hour
  3. extractionthe mixture was extracted three times with ethyl acetate
  4. washThe organic layer was washed twice 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 (n-hexane:ethyl acetate=6:1)

Sources & evidence

ORD record
ord-6148103cca70466693ba03e5d8d65b6f
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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