1-Iodopentane → 2-[4-[N-acetyl-N-(1-pentyl)amino]-3-fluorophenyl]-6,8-difluoro-7-methyl-5-(1-pentylamino)-4H-1-benzopyran-4-one

HRID 1736174Notes

Reaction equation

HRID 1736174 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]3[C:21]([F:22])=[C:20]([CH3:23])[C:19]([F:24])=[C:18]([NH2:25])[C:14]=3[C:15](=[O:17])[CH:16]=2)=[CH:7][C:6]=1[F:26])(=[O:3])[CH3:2].[H-].[Na+].I[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].[Cl-].[NH4+]>CN(C)C=O>[C:1]([N:4]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]3[C:21]([F:22])=[C:20]([CH3:23])[C:19]([F:24])=[C:18]([NH:25][CH2:7][CH2:6][CH2:5][CH2:10][CH3:9])[C:14]=3[C:15](=[O:17])[CH:16]=2)=[CH:7][C:6]=1[F:26])[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 123351-Iodopentane2×HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 194349512-(4-acetylamino-3-fluorophenyl)-5-amino-6,8-difluoro-7-methyl-4H-1-benzopyran-4-one

Product 1

HCID 194348722-[4-[N-acetyl-N-(1-pentyl)amino]-3-fluorophenyl]-6,8-difluoro-7-methyl-5-(1-pentylamino)-4H-1-benzopyran-4-oneYield 43.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

510 mg (1.41 mmol) of 2-(4-acetylamino-3-fluorophenyl)-5-amino-6,8-difluoro-7-methyl-4H-1-benzopyran-4-one obtained in Example 109 (1) was dissolved in 30 mL of dimethylformamide under argon atmosphere, 58 mg (1.5 mmol) of sodium hydride (60% oil dispersion) and 0.37 mL (2.8 mmol) of 1-iodopentane were added under ice-cooling and the mixture was stirred at room temperature for 4 hours. The reaction solution was cooled on ice, 117 mg (2.93 mmol) of sodium hydride (60% oil dispersion) and 0.37 mL (2.8 mmol) of 1-iodopentane were added and the mixture was stirred at room temperature for 50 minutes. An aqueous solution of ammonium chloride 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 silica gel column chromatography (chloroform) to give 153 mg of 2-[4-[N-acetyl-N-(1-pentyl)amino]-3-fluorophenyl]-6,8-difluoro-7-methyl-5-(1-pentylamino)-4H-1-benzopyran-4-one (yield: 22%).

Workup

  1. temperaturecooling
  2. additionwere added
  3. stirringthe mixture was stirred at room temperature for 50 minutes
  4. extractionthe mixture was extracted twice with ethyl acetate
  5. washThe organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (chloroform)

Sources & evidence

ORD record
ord-baf27851240c466da863f254f003e25b
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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