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

HRID 1979358Notes

Reaction equation

HRID 1979358 reaction equation
[C:1]1([CH3:48])[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][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:23])[CH2:13][CH:12]([NH:32][C:33]([NH:35][C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([O:44]CC)=[O:43])[CH:37]=3)=[O:34])[C:11]2=[O:47])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.O.[OH-].[Li+].O1CCCC1>CO>[C:1]1([CH3:48])[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][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:23])[CH2:13][CH:12]([NH:32][C:33](=[O:34])[NH:35][C:36]3[CH:37]=[C:38]([CH:39]=[CH:40][CH:41]=3)[C:42]([OH:44])=[O:43])[C:11]2=[O:47])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 212015541-[1-(2-Toluoylmethyl)-2-oxo-5-benzyloxycarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea

Product 1

HCID 212020013-[3-[1-(2-toluoylmethyl)-2-oxo-5-benzyloxycarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]ureido]benzoic acidYield 72.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-[1-(2-Toluoylmethyl)-2-oxo-5-benzyloxycarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea (435 mg) was dissolved in methanol (20 ml), aqueous lithium hydroxide monohydrate (141 mg) solution (10 ml) and tetrahydrofuran (10 ml) were added, the mixture was refluxed for 2 hours. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in water (150 ml), washed with diethyl ether (100 ml), acidified with 1N hydrochloric acid, and extracted with methylene chloride. The organic layer was dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, n-hexane was added to the residue for trituration, and collected by filtration, to thereby obtain 301 mg of the titled compound (Yield: 72.5%).

Workup

  1. temperaturethe mixture was refluxed for 2 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in water (150 ml)
  4. washwashed with diethyl ether (100 ml)
  5. extractionextracted with methylene chloride
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure, n-hexane
  8. additionwas added to the residue for trituration
  9. filtrationcollected by filtration

Sources & evidence

ORD record
ord-d56bbb6032f940b0a2ec7676b00fb222
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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