Tetrahydrofuran → 3-[3-[1-(2-toluoylmethyl)-2-oxo-5-acetyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]ureido]benzoic acid

HRID 1979409Notes

Reaction equation

HRID 1979409 reaction equation
[C:1]1([CH3:41])[C:2]([C:7]([CH2:9][N:10]2[C:16]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:15]=3[N:14]([C:22](=[O:24])[CH3:23])[CH2:13][CH:12]([NH:25][C:26]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([O:37]CC)=[O:36])[CH:30]=3)=[O:27])[C:11]2=[O:40])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.O.[OH-].[Li+].O1CCCC1>CO>[C:1]1([CH3:41])[C:2]([C:7]([CH2:9][N:10]2[C:16]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:15]=3[N:14]([C:22](=[O:24])[CH3:23])[CH2:13][CH:12]([NH:25][C:26](=[O:27])[NH:28][C:29]3[CH:30]=[C:31]([CH:32]=[CH:33][CH:34]=3)[C:35]([OH:37])=[O:36])[C:11]2=[O:40])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 212016041-[1-(2-Toluoylmethyl)-2-oxo-5-acetyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea

Product 1

HCID 212017063-[3-[1-(2-toluoylmethyl)-2-oxo-5-acetyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]ureido]benzoic acidYield 58.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-[1-(2-Toluoylmethyl)-2-oxo-5-acetyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea (670 mg) was dissolved in methanol (32 ml), aqueous lithium hydroxide monohydrate (253 mg) solution (16 ml) and tetrahydrofuran (16 ml) were added, and the mixture was refluxed for 45 minutes, the reaction mixture was concentrated under reduced pressure, the residue was dissolved in water (150 ml), the solution was washed with diethyl ether, acidified with 1N hydrochloric acid, and extracted with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, diisoproryl ether was added to the residue for trituration, collected by filtration, to thereby obtain 370 mg of the titled compound.

Workup

  1. temperaturethe mixture was refluxed for 45 minutes
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in water (150 ml)
  4. washthe solution was washed with diethyl ether
  5. extractionextracted with methylene chloride
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure, diisoproryl ether
  9. additionwas added to the residue for trituration
  10. filtrationcollected by filtration

Sources & evidence

ORD record
ord-1dee8a9e4b764233872d6f36491b9380
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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