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

HRID 1979441Notes

Reaction equation

HRID 1979441 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:15]=[C:16]([CH:22]=[CH:23][CH:24]=1)[C:17]([O:19][CH2:20][CH3:21])=[O:18].C(N(CC)CC)C.[C:32]([C:36]([CH2:38][N:39]1[C:45]2[CH:46]=[C:47]([CH3:50])[CH:48]=[CH:49][C:44]=2[N:43]([CH:51]2[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]2)[CH2:42][CH:41]([NH2:57])[C:40]1=[O:58])=[O:37])([CH3:35])([CH3:34])[CH3:33]>O1CCCC1>[C:32]([C:36]([CH2:38][N:39]1[C:45]2[CH:46]=[C:47]([CH3:50])[CH:48]=[CH:49][C:44]=2[N:43]([CH:51]2[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]2)[CH2:42][CH:41]([NH:57][C:2]([NH:13][C:14]2[CH:24]=[CH:23][CH:22]=[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:15]=2)=[O:4])[C:40]1=[O:58])=[O:37])([CH3:35])([CH3:33])[CH3:34]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11400Ethyl 3-aminobenzoateHCID 94429TriphosgeneHCID 212019271-tert-butylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212018501-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-ethoxycarbonylphenyl)ureaYield 164.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Triphosgene (122 mg) was added to a solution of ethyl 3-aminobenzoate (182 mg) in tetrahydrofuran (10 ml) under ice-cooling, triethylamine (98 μl) was added thereto five times (total: 490 μl), the mixture was stirred at room temperature for 5 minutes. A solution of 1-tert-butylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (393 mg) in anhydrous tetrahydrofuran (5 ml) was added to the mixture under ice-cooling, stirred at room temperature for 30 minutes. Ice-water was added to the reaction mixture, extracted with methylene chloride. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and a mixed solvent of n-hexane and ethyl acetate(n-hexane:ethyl acetate=1:1) was added to the residue for crystallization, collected by filtration, to thereby obtain 380 mg of the title compound.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringstirred at room temperature for 30 minutes
  4. extractionextracted with methylene chloride
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. additiona mixed solvent of n-hexane and ethyl acetate(n-hexane:ethyl acetate=1:1) was added to the residue for crystallization
  9. filtrationcollected by filtration

Sources & evidence

ORD record
ord-8d6990c42b9b4626981a9205ef4a6054
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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