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

HRID 1979419Notes

Reaction equation

HRID 1979419 reaction equation
[C:1]1([CH3:45])[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]([C:24]3[O:25][CH:26]=[CH:27][CH:28]=3)=[O:23])[CH2:13][CH:12]([NH:29][C:30]([NH:32][C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([O:41]CC)=[O:40])[CH:34]=3)=[O:31])[C:11]2=[O:44])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.O.[OH-].[Li+].O1CCCC1>CO>[C:1]1([CH3:45])[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]([C:24]3[O:25][CH:26]=[CH:27][CH:28]=3)=[O:23])[CH2:13][CH:12]([NH:29][C:30](=[O:31])[NH:32][C:33]3[CH:34]=[C:35]([CH:36]=[CH:37][CH:38]=3)[C:39]([OH:41])=[O:40])[C:11]2=[O:44])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 212018391-[1-(2-toluoylmethyl)-2-oxo-5-(furan-2-ylcarbonyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea

Product 1

HCID 212016563-[3-[1-(2-toluoylmethyl)-2-oxo-5-(furan-2-ylcarbonyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]ureido]benzoic acidYield 57.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-[1-(2-Toluoylmethyl)-2-oxo-5-(furan-2-ylcarbonyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea (429 mg) was dissolved in methanol (22 ml), aqueous lithium hydroxide monohydrate (148 mg) solution (11 ml) and tetrahydrofuran (11 ml) were added, and the mixture was refluxed for one hour. 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, and the solvent was evaporated under reduced pressure. Isoproryl ether was added to the residue for trituration,collected by filtration, to thereby obtain 237 mg of the titled compound.

Workup

  1. temperaturethe mixture was refluxed for one hour
  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
  9. additionIsoproryl ether was added to the residue for
  10. filtrationtrituration,collected by filtration

Sources & evidence

ORD record
ord-dfcaeed686d64a73949acb418d70f15d
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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