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

HRID 1979405Notes

Reaction equation

HRID 1979405 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])[C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:13][CH:12]([NH:28][C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([Cl:38])=[C:34]([C:39]([O:41]C)=[O:40])[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>[Cl:38][C:35]1[CH:36]=[CH:37][C:32]([NH:31][C:29]([NH:28][CH:12]2[C:11](=[O:43])[N:10]([CH2:9][C:7]([C:2]3[C:1]([CH3:44])=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:8])[C:16]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:15]=3[N:14]([C:22](=[O:27])[C:23]([CH3:25])([CH3:24])[CH3:26])[CH2:13]2)=[O:30])=[CH:33][C:34]=1[C:39]([OH:41])=[O:40]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 212018891-[1-(2-toluoylmethyl)-2-oxo-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-methoxycarbonyl-4-chlorophenyl)urea

Product 1

HCID 212019702-chloro-5-[3-[1-(2-toluoylmethyl)-2-oxo-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]ureido]benzoic acidYield 64.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-[1-(2-Toluoylmethyl)-2-oxo-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-methoxycarbonyl-4-chlorophenyl)urea (691 mg) was dissolved in methanol (30 ml), aqueous lithium hydroxide monohydrate (234 mg) solution (15 ml) and tetrahydrofuran (15 ml) were added, the mixture was refluxed for one hour. The reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid was added, and extracted with methylene chloride. The organic layer was dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, and diisopropyl ether was added to the residue for trituration, collected by filtration, to thereby obtain 437 mg of the titled compound.

Workup

  1. temperaturethe mixture was refluxed for one hour
  2. concentrationThe reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid
  3. additionwas added
  4. extractionextracted with methylene chloride
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure, and diisopropyl ether
  7. additionwas added to the residue for trituration
  8. filtrationcollected by filtration

Sources & evidence

ORD record
ord-84eb2f24984d47fb98ebdb524083dfab
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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