Water → HCID 15347010, compound

HRID 1736133Notes

Reaction equation

HRID 1736133 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][NH:8][C:9]1[C:14]2[C:15](=[O:29])[CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([N:25]([CH3:27])[CH3:26])=[C:21]([F:28])[CH:20]=3)[O:18][C:13]=2[C:12]([F:30])=[CH:11][C:10]=1[F:31].[NH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1.O>O1CCCC1>[F:31][C:10]1[CH:11]=[C:12]([F:30])[C:13]2[O:18][C:17]([C:19]3[CH:24]=[CH:23][C:22]([N:25]([CH3:27])[CH3:26])=[C:21]([F:28])[CH:20]=3)=[CH:16][C:15](=[O:29])[C:14]=2[C:9]=1[NH:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 962WaterHCID 31268Pyrrolidine4×HCID 15347008HCID 15347008, compound

Product 1

HCID 15347010HCID 15347010, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

500 mg (1.01 mmol) of Compound 59 obtained in Example 59 was dissolved in 5 ml of tetrahydrofuran, 0.17 ml of pyrrolidine was added and the mixture was heated at reflux for 5.5 hours. At 1 hour and 1.7 hours after the reaction was started, each 0.17 ml of pyrrolidine was added. At 3.5 hours and 4.5 hours, each 0.17 ml of pyrrolidine was added. At 3.5 hours and 4.5 hours, each 0.08 ml of pyrrolidine was added. Water was added to the reaction solution and the mixture was extracted with chloroform. 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 triturated with n-hexane to give Compound 63 which was converted into hydrochloride according to the same manner as that in Example 62 to give 465 mg (83%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 5.5 hours
  3. custom1.7 hours
  4. waitAt 3.5 hours
  5. waitAt 3.5 hours
  6. extractionthe mixture was extracted with chloroform
  7. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
  8. dry with materialdried over anhydrous sodium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (chloroform:methanol:triethylamine=90:10:1)
  11. customtriturated with n-hexane

Sources & evidence

ORD record
ord-641545f401254b87ba773a301dd2589a
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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