Triethylamine → 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

HRID 1979426Notes

Reaction equation

HRID 1979426 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(N(CC)CC)C.[C:32]1([CH3:63])[C:33]([C:38]([CH2:40][N:41]2[C:47]3[CH:48]=[C:49]([CH3:52])[CH:50]=[CH:51][C:46]=3[N:45]([C:53]([CH:55]3[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]3)=[O:54])[CH2:44][CH:43]([NH2:61])[C:42]2=[O:62])=[O:39])=[CH:34][CH:35]=[CH:36][CH:37]=1>O1CCCC1>[C:32]1([CH3:63])[C:33]([C:38]([CH2:40][N:41]2[C:47]3[CH:48]=[C:49]([CH3:52])[CH:50]=[CH:51][C:46]=3[N:45]([C:53]([CH:55]3[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]3)=[O:54])[CH2:44][CH:43]([NH:61][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:42]2=[O:62])=[O:39])=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11400Ethyl 3-aminobenzoateHCID 94429TriphosgeneHCID 212019781-(2-toluoylmethyl)-2-oxo-3-amino-5-cyclohexylcarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212018771-[1-(2-toluoylmethyl)-2-oxo-5-cyclohexylcarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)ureaYield 156.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl 3-aminobenzoate (252 mg) was dissolved in tetrahydrofuran (40 ml), triphosgene (152 mg) was added under ice-cooling, subsequently, triethylamine (132 μl) was added five times every 3 minutes, a solution of 1-(2-toluoylmethyl)-2-oxo-3-amino-5-cyclohexylcarbonyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (600 mg) in tetrahydrofuran (20 ml), and the reaction mixture was allowed to come to room temperature and additionally stirred for 2 hours. The reaction mixture was concentrated under reduced pressure, water (50 ml) was added to the residue, extracted with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=2:1), to thereby obtain 500 mg of the titled compound.

Workup

  1. temperaturecooling
  2. customto come to room temperature
  3. concentrationThe reaction mixture was concentrated under reduced pressure, water (50 ml)
  4. additionwas added to the residue
  5. extractionextracted with methylene chloride
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-332d97344efc43f88fada8d44bbf0e1f
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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