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

HRID 1979399Notes

Reaction equation

HRID 1979399 reaction equation
[C:1]1([CH3:44])[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:27])[CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:13][CH:12]([NH:28][C:29]([NH:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([O:40]CC)=[O:39])[CH:33]=3)=[O:30])[C:11]2=[O:43])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.O.[OH-].[Li+].O1CCCC1>CO>[C:1]1([CH3:44])[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:27])[CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:13][CH:12]([NH:28][C:29](=[O:30])[NH:31][C:32]3[CH:33]=[C:34]([CH:35]=[CH:36][CH:37]=3)[C:38]([OH:40])=[O:39])[C:11]2=[O:43])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 696936151-(1-(2-toluoylmethyl)-2-oxo-5-isovaleryl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea

Product 1

HCID 212016793-[3-[1-(2-toluoylmethyl)-2-oxo-5-isovaleryl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]ureido]benzoic acidYield 56.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-[1-(2-Toluoylmethyl)-2-oxo-5-isovaleryl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea (296 mg) was dissolved in methanol (14 ml), aqueous lithium hydroxide monohydrate (62 mg) solution (7 ml) and tetrahydrofuran (7 ml) were added, and the mixture was refluxed for 45 minutes. The reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid was added, and extracted with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. Isopropyl ether was added to the residue for trituration, collected by filtration, to thereby obtain 160 mg of the titled compound.

Workup

  1. temperaturethe mixture was refluxed for 45 minutes
  2. concentrationThe reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid
  3. additionwas added
  4. extractionextracted with methylene chloride
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. additionIsopropyl ether was added to the residue for trituration
  9. filtrationcollected by filtration

Sources & evidence

ORD record
ord-38e5bd42b66540bb8f10a6d053023b69
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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