Triethylamine → 1-[1-(2-toluoylmethyl)-2-oxo-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea

HRID 1979431Notes

Reaction equation

HRID 1979431 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([CH3:61])[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]([CH:53]3[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]3)[CH2:44][CH:43]([NH2:59])[C:42]2=[O:60])=[O:39])=[CH:34][CH:35]=[CH:36][CH:37]=1>O1CCCC1.O>[C:32]1([CH3:61])[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]([CH:53]3[CH2:54][CH2:55][CH2:56][CH2:57][CH2:58]3)[CH2:44][CH:43]([NH:59][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:60])=[O:39])=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11400Ethyl 3-aminobenzoateHCID 94429TriphosgeneHCID 212018461-(2-toluoylmethyl)-2-oxo-3-amino-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212015691-[1-(2-toluoylmethyl)-2-oxo-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)ureaYield 202.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl 3-aminobenzoate (100 mg) was dissolved in tetrahydrofuran (5 ml), the solution was cooled on ice, triphosgene (65 mg) was added thereto at internal temperature 5° C., triethylamine (220 mg) was added thereto at 3 minutes intervals, the mixture was allowed to come to room temperature and stirred for 10 minutes. A solution of 1-(2-toluoylmethyl)-2-oxo-3-amino-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (820 mg) in tetrahydrofuran (5 ml) was added, additionally stirred for one hour. Water was added to the reaction mixture, extracted with methylene chloride. The organic layer was successively washed with water and saturated brine, dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=3:1), to thereby obtain 265 mg of the titled compound (Yield 81%).

Workup

  1. additionwas added
  2. customto come to room temperature
  3. stirringadditionally stirred for one hour
  4. extractionextracted with methylene chloride
  5. washThe organic layer was successively washed with water and saturated brine
  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(n-hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-fc023937dd14415dae35dcb85717ae73
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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