Triethylamine → 1-(1-tert-butylcarbonylmethyl-2-oxo-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-benzyloxycarbonylphenyl)urea

HRID 1979322Notes

Reaction equation

HRID 1979322 reaction equation
C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:8])C=CC=CC=1.C([N:20]([CH2:23]C)CC)C.[CH2:25]([O:32][C:33](=[O:43])[C:34]1[CH:42]=[CH:41][CH:40]=[C:36](C(O)=O)[CH:35]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[C:44]([C:48]([CH2:50][N:51]1[C:57]2[CH:58]=[CH:59][CH:60]=[CH:61][C:56]=2[N:55]([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH2:54][CH:53]([NH2:68])[C:52]1=[O:69])=[O:49])([CH3:47])([CH3:46])[CH3:45]>O1CCOCC1>[C:44]([C:48]([CH2:50][N:51]1[C:57]2[CH:58]=[CH:59][CH:60]=[CH:61][C:56]=2[N:55]([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH2:54][CH:53]([NH:68][C:23]([NH:20][C:36]2[CH:40]=[CH:41][CH:42]=[C:34]([C:33]([O:32][CH2:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[O:43])[CH:35]=2)=[O:8])[C:52]1=[O:69])=[O:49])([CH3:47])([CH3:45])[CH3:46]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 13918608Isophthalic acid benzyl esterHCID 212016651-tert-butylcarbonylmethyl-2-oxo-3-amino-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212019451-(1-tert-butylcarbonylmethyl-2-oxo-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-benzyloxycarbonylphenyl)ureaYield 54%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
60 °C

Procedure

Diphenylphosphoryl azide (1.1 g) and triethylamine (0.62 ml) were added to a solution of isophthalic acid mono-benzyl ester (792 mg) in dioxane (20 ml), the mixture was stirred internal temperature at 60° C. for 20 minutes and internal temperature at 80° C. for 2 hours. After the reaction mixture was allowed to cool to room temperature, a solution of 1-tert-butylcarbonylmethyl-2-oxo-3-amino-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (723 mg) obtained from Step 1 of Example 33 in dioxane (5 ml) was added to the reaction mixture. The reaction mixture was stirred at room temperature for 30 minutes. The mixture was concentrated under reduced pressure, chloroform (50 ml) was added to the resultant residue, and washed with saturated aqueous sodium bicarbonate. After dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, the mixed solvent of isopropyl ether and ethyl acetate was added to the residue for trituration, to thereby obtain 674 mg of the title compound as a colorless solid (Yield: 54%).

Workup

  1. waitinternal temperature at 80° C. for 2 hours
  2. temperatureto cool to room temperature
  3. stirringThe reaction mixture was stirred at room temperature for 30 minutes
  4. concentrationThe mixture was concentrated under reduced pressure, chloroform (50 ml)
  5. additionwas added to the resultant residue
  6. washwashed with saturated aqueous sodium bicarbonate
  7. dry with materialAfter dried over anhydrous sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. additionthe mixed solvent of isopropyl ether and ethyl acetate was added to the residue for trituration

Sources & evidence

ORD record
ord-609e06deaa35452eb9e5af45e50cb18f
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

Loading…