Water → 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methyl-5-(3-methylbutylamino)-4H-1-benzopyran-4-one

HRID 1736178Notes

Reaction equation

HRID 1736178 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])=[C:4]([CH3:28])[C:3]=1[F:29].[H-].[Na+].Br[CH2:33][CH2:34][CH:35]([CH3:37])[CH3:36].O>CN(C)C=O>[F:29][C:3]1[C:4]([CH3:28])=[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][CH2:33][CH2:34][CH:35]([CH3:37])[CH3:36]

Participants

6

Reactant 4

HCID 962WaterHCID 78911-Bromo-3-methylbutaneHCID 24758Sodium hydrideHCID 194349955-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methyl-4H-1-benzopyran-4-one

Product 1

HCID 194347986,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methyl-5-(3-methylbutylamino)-4H-1-benzopyran-4-oneYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.03 g (2.54mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methyl-4H-1-benzopyran-4-one obtained in Example 107 (1) was dissolved in 20 mL of dimethylformamide under argon atmosphere, 308 mg (7.62 mmol) of sodium hydride (60% oil dispersion) and 0.77 mL (6.4 mmol) of 1-bromo-3-methylbutane were added and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction solution, the mixture was extracted once with ethyl acetate, the organic layer was washed 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 708 mg of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methyl-5-(3-methylbutylamino)-4H-1-benzopyran-4-one (yield: 59%).

Workup

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

Sources & evidence

ORD record
ord-368df6017a0c432389d657d0335562c2
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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