Water → HCID 15347007, compound

HRID 1736126Notes

Reaction equation

HRID 1736126 reaction equation
C([N:4]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[O:19][C:20]3[C:28]([F:29])=[CH:27][C:26]([F:30])=[C:25]([NH2:31])[C:21]=3[C:22](=[O:24])[CH:23]=2)=[CH:14][C:13]=1[F:32])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]Br)(=O)C.[NH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1.O>O1CCCC1>[NH2:31][C:25]1[C:21]2[C:22](=[O:24])[CH:23]=[C:18]([C:15]3[CH:16]=[CH:17][C:12]([NH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][N:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)=[C:13]([F:32])[CH:14]=3)[O:19][C:20]=2[C:28]([F:29])=[CH:27][C:26]=1[F:30]

Participants

5

Reactant 3

HCID 962WaterHCID 31268PyrrolidineHCID 19434847HCID 19434847, compound

Product 1

HCID 15347007HCID 15347007, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

500 mg (1.07 mmol) of 5-amino-2-[4-(6-bromohexylamino)-3-fluorophenyl]-6,8-difluoro-4H-1-benzopyran-4-one obtained in Example 52 was dissolved in 15 ml of tetrahydrofuran, 0.891 ml of pyrrolidine was added and the mixture was heated at reflux for 1.5 hours. Water was added to the reaction solution and the mixture was extracted with a mixed solvent of chloroform and methanol. 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 (chloroform:methanol:triethylamine=90:10:1) and recrystallized from chloroform/n-hexane to give Compound 54 which was converted into hydrochloride according to the same manner as that in Example 16 to give 88 mg (17%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 1.5 hours
  3. extractionthe mixture was extracted with a mixed solvent of chloroform and methanol
  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 (chloroform:methanol:triethylamine=90:10:1)
  8. customrecrystallized from chloroform/n-hexane

Sources & evidence

ORD record
ord-1aaa974e44aa44bf91b8e12f8db2064a
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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