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

HRID 1736169Notes

Reaction equation

HRID 1736169 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].CN(C)C=O.[H-].[Na+].I[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]>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][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 125271-IodohexaneHCID 24758Sodium hydrideHCID 194349955-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methyl-4H-1-benzopyran-4-one

Product 1

HCID 194348486,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-(1-hexylamino)-7-methyl-4H-1-benzopyran-4-oneYield 54%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

653 mg (1.62 mmol) of the above 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methyl-4H-1-benzopyran-4-one was dissolved ion 20 mL of dimethylformamide under argon atmosphere, 200 mg (5.00 mmol) of sodium hydride (60% oil dispersion) and 0.48 mL (3.2 mmol) of 1-iodohexane were added under ice-cooling and the mixture was stirred at room temperature for 20 hours. Water was added to the reaction solution and the mixture was extracted twice 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 medium pressure liquid chromatography to give 422 mg of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-(1-hexylamino)-7-methyl-4H-1-benzopyran-4-one (yield: 54%).

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted twice 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 medium pressure liquid chromatography

Sources & evidence

ORD record
ord-b3aca784d2274876a6ad46a447ee9d14
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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