Hydrochloric Acid → 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

HRID 1979357Notes

Reaction equation

HRID 1979357 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:14](Cl)([O:16]C(=O)OC(Cl)(Cl)Cl)Cl.[C:25]1([CH3:58])[C:26]([C:31]([CH2:33][N:34]2[C:40]3[CH:41]=[C:42]([CH3:45])[CH:43]=[CH:44][C:39]=3[N:38]([C:46]([O:48][CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[O:47])[CH2:37][CH:36]([NH2:56])[C:35]2=[O:57])=[O:32])=[CH:27][CH:28]=[CH:29][CH:30]=1.Cl>O1CCCC1.O.C(N(CC)CC)C>[C:25]1([CH3:58])[C:26]([C:31]([CH2:33][N:34]2[C:40]3[CH:41]=[C:42]([CH3:45])[CH:43]=[CH:44][C:39]=3[N:38]([C:46]([O:48][CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[O:47])[CH2:37][CH:36]([NH:56][C:14]([NH:1][C:2]3[CH:12]=[CH:11][CH:10]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH:3]=3)=[O:16])[C:35]2=[O:57])=[O:32])=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11400Ethyl 3-aminobenzoateHCID 94429TriphosgeneHCID 212015721-(2-toluoylmethyl)-2-oxo-3-amino-5-benzyloxycarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212015541-[1-(2-Toluoylmethyl)-2-oxo-5-benzyloxycarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)ureaYield 239.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

Ethyl 3-aminobenzoate (4.29 g) was dissolved in tetrahydrofuran (600 ml), triphosgene (2.54 g) was added under ice-cooling, triethylamine (2.19 ml) was added thereto five times every 3 minutes after divided into five portions. A solution of 1-(2-toluoylmethyl)-2-oxo-3-amino-5-benzyloxycarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (9.78 g) in tetrahydrofuran (200 ml) was added, the mixture was stirred for 30 minutes, subsequently, stirred overnight at room temperature. The reaction mixture was poured into water (3 L), acidified with 1N hydrochloric acid, extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium bicarbonate, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography(chloroform:ethyl acetate=2:1), to thereby obtain 13.3 g of the titled compound.

Workup

  1. temperaturecooling
  2. customevery 3 minutes
  3. stirringsubsequently, stirred overnight at room temperature
  4. extractionextracted with methylene chloride
  5. washThe organic layer was washed with saturated aqueous sodium bicarbonate
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography(chloroform:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-09a94a0149e44852b8bf57c658b971a9
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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