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

HRID 1736137Notes

Reaction equation

HRID 1736137 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+].I[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37].[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][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]

Participants

6

Reactant 4

HCID 125271-Iodohexane2×HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 194349345-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one

Product 1

HCID 194349046,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-hexylamino-4H-1-benzopyran-4-oneYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

505 mg (1.29 mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one was dissolved in 15 ml of dimethylformamide under argon atmosphere, 156 mg of sodium hydride (60% oil dispersion) and 0.38 ml of 1-iodohexane were added under ice-cooling and the mixture was stirred at the same temperature for 30 minutes. 0.19 ml of 1-iodohexane was added and the mixture was stirred for additional 2 hours. 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 487 mg (79%) of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-hexylamino-4H-1-benzopyran-4-one.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for additional 2 hours
  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-e2c846f706ed4a04a2706e85d187a374
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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