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

HRID 1979427Notes

Reaction equation

HRID 1979427 reaction equation
[C:1]1([CH3:46])[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]([CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=[O:23])[CH2:13][CH:12]([NH:30][C:31]([NH:33][C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([O:42]CC)=[O:41])[CH:35]=3)=[O:32])[C:11]2=[O:45])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.O.[OH-].[Li+].O1CCCC1>CO>[C:1]1([CH3:46])[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]([CH:24]3[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]3)=[O:23])[CH2:13][CH:12]([NH:30][C:31](=[O:32])[NH:33][C:34]3[CH:35]=[C:36]([CH:37]=[CH:38][CH:39]=3)[C:40]([OH:42])=[O:41])[C:11]2=[O:45])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 212018771-[1-(2-toluoylmethyl)-2-oxo-5-cyclohexylcarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea

Product 1

HCID 212020033-[3-[1-(2-toluoylmethyl)-2-oxo-5-cyclohexylcarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]ureido]benzoic acidYield 50.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-[1-(2-Toluoylmethyl)-2-oxo-5-cyclohexylcarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea (500 mg) was dissolved in methanol (24 ml), aqueous lithium hydroxide monohydrate (168 mg) solution (12 ml) and tetrahydrofuran (12 ml) were added, and the mixture was refluxed for 30 minutes. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in water (50 ml), the solution was washed with diethyl ether, acidified with 1N hydrochloric acid, and extracted with methylene chloride (50ml). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, and isoproryl ether was added to the residue for trituration, collected by filtration, to thereby obtain 240 mg of the titled compound.

Workup

  1. temperaturethe mixture was refluxed for 30 minutes
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in water (50 ml)
  4. washthe solution was washed with diethyl ether
  5. extractionextracted with methylene chloride (50ml)
  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, and isoproryl ether
  9. additionwas added to the residue for trituration
  10. filtrationcollected by filtration

Sources & evidence

ORD record
ord-0f6da2075aa34059ac0a0c586fc9034d
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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