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

HRID 1979397Notes

Reaction equation

HRID 1979397 reaction equation
[C:1]1([CH3:43])[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]([CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25])[CH2:13][CH:12]([NH:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([O:39]CC)=[O:38])[CH:32]=3)=[O:29])[C:11]2=[O:42])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.O.[OH-].[Li+].O1CCCC1>CO>[C:1]1([CH3:43])[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]([CH2:22][CH:23]=[C:24]([CH3:25])[CH3:26])[CH2:13][CH:12]([NH:27][C:28](=[O:29])[NH:30][C:31]3[CH:32]=[C:33]([CH:34]=[CH:35][CH:36]=3)[C:37]([OH:39])=[O:38])[C:11]2=[O:42])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 212018081-[1-(2-toluoylmethyl)-2-oxo-5-(3-methyl-2-butenyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea

Product 1

HCID 212015803-[3-[1-(2-toluoylmethyl)-2-oxo-5-(3-methyl-2-butenyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]ureido]benzoic acidYield 78.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-[1-(2-Toluoylmethyl)-2-oxo-5-(3-methyl-2-butenyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea (310 mg) was dissolved in methanol (16 ml), aqueous lithium hydroxide monohydrate (112 mg) solution (8 ml) and tetrahydrofuran (8 ml) were added, and the mixture was refluxed for 50 minutes. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in water (150 ml), washed with diethyl ether, 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, and a mixed solvent of diisopropyl ether and n-hexane were added to the residue for trituration, collected by filtration, to thereby obtain 230 mg of the titled compound (Yield: 78.3%).

Workup

  1. temperaturethe mixture was refluxed for 50 minutes
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in water (150 ml)
  4. washwashed with diethyl ether
  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
  8. additiona mixed solvent of diisopropyl ether and n-hexane were added to the residue for trituration
  9. filtrationcollected by filtration

Sources & evidence

ORD record
ord-2097d966245c4a69bd80bf158cf459d0
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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