1-Bromo-3-methylbutane → 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-isopentylamino-4H-1-benzopyran-4-one

HRID 1736140Notes

Reaction equation

HRID 1736140 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+].[CH2:31](Br)[CH2:32][CH:33]([CH3:35])[CH3:34].[Cl-].[NH4+]>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][CH2:31][CH2:32][CH:33]([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 78911-Bromo-3-methylbutane2×HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 194349345-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one

Product 1

HCID 194348586,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-isopentylamino-4H-1-benzopyran-4-oneYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

510 mg (1.32 mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one obtained in Example 66 was dissolved in 15 ml of dimethylformamide under argon atmosphere, 160 mg of sodium hydride (60% oil dispersion) and 0.35 ml of isoamyl bromide were added under ice-cooling and the mixture was stirred at room temperature for 1.5 hours. 0.16 ml of isoamyl bromide was added and the mixture was stirred for additional 1 hour. An aqueous saturated solution of ammonium chloride was added to the reaction solution and the mixture was extracted twice with ethyl acetate. The organic layer was washed 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=5:1) to give 310 mg (51%) of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-isopentylamino-4H-1-benzopyran-4-one.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for additional 1 hour
  3. extractionthe mixture was extracted twice with ethyl acetate
  4. washThe organic layer was washed 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=5:1)

Sources & evidence

ORD record
ord-1f559c0f55684b269993354fdbf2df64
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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