Triethylamine → 1-(1-cyclohexylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonylphenyl)urea

HRID 1979474Notes

Reaction equation

HRID 1979474 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:24]=[CH:25][CH:26]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(N(CC)CC)C.[CH:34]1([C:40]([CH2:42][N:43]2[C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=3[N:47]([CH:54]3[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]3)[CH2:46][CH:45]([NH2:60])[C:44]2=[O:61])=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>O1CCCC1>[CH:34]1([C:40]([CH2:42][N:43]2[C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=3[N:47]([CH:54]3[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59]3)[CH2:46][CH:45]([NH:60][C:2]([NH:13][C:14]3[CH:26]=[CH:25][CH:24]=[C:16]([C:17]([O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:18])[CH:15]=3)=[O:4])[C:44]2=[O:61])=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 2737408tert-Butyl-3-aminobenzoateHCID 212018931-cyclohexylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212018681-(1-cyclohexylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonylphenyl)ureaYield 230%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Triphosgene (122 mg) was added to a solution of tert-butyl 3-aminobenzoate (213 mg) in anhydrous tetrahydrofuran (30 ml) at 0° C., triethylamine (0.49 ml) was added thereto at 0° C. five times each 98 μl over 15 minutes. After the mixture was stirred at room temperature for 5 minutes, a solution of 1-cyclohexylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (395 mg) in anhydrous tetrahydrofuran (10 ml) was added at 0° C., the resultant mixture was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure, and water was added to the residue, extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, diisopropyl ether was added to the residue for crystallization, collected by filtration, to thereby obtain 570 mg of the title compound (Yield: 92%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and water
  2. additionwas added to the residue
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure, diisopropyl ether
  7. additionwas added to the residue for crystallization
  8. filtrationcollected by filtration

Sources & evidence

ORD record
ord-1d64fdf427064726afeff333b65e9854
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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