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

HRID 1979371Notes

Reaction equation

HRID 1979371 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]=[C:59]([CH3:62])[CH:60]=[CH:61][C:56]=2[N:55]([C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH2:54][CH:53]([NH2:69])[C:52]1=[O:70])=[O:49])([CH3:47])([CH3:46])[CH3:45]>O1CCOCC1>[C:44]([C:48]([CH2:50][N:51]1[C:57]2[CH:58]=[C:59]([CH3:62])[CH:60]=[CH:61][C:56]=2[N:55]([C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH2:54][CH:53]([NH:69][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:70])=[O:49])([CH3:47])([CH3:45])[CH3:46]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 13918608Isophthalic acid benzyl esterHCID 212019411-tert-butylcarbonylmethyl-2-oxo-3-amino-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 21201662(+)-1-(1-tert-butylcarbonylmethyl-2-oxo-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-benzyloxycarbonylphenyl)urea

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
60 °C

Procedure

Diphenylphosphoryl azide (1.38 g) and triethylamine (0.77 ml) were added to a solution of isophthalic acid benzyl ester (1.15 g) in anhydrous dioxane (20 ml), the mixture was stirred at 60° C. for 30 minutes and subsequently stirred at internal temperature 80° C. for one hour. The reaction mixture was allowed to come to room temperature, a solution of (+)-1-tert-butylcarbonylmethyl-2-oxo-3-amino-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (1.1 g) in anhydrous dioxane (20 ml) was added thereto, the mixture was stirred for 2 hours at room temperature. The resultant mixture was concentrated under reduced pressure, chloroform was added, the mixture was washed succesively with saturated aqueous sodium bicarbonate and saturated brine, and 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=2:1), to thereby obtain 622 mg of the titled compound.

Workup

  1. stirringsubsequently stirred at internal temperature 80° C. for one hour
  2. customto come to room temperature
  3. stirringthe mixture was stirred for 2 hours at room temperature
  4. concentrationThe resultant mixture was concentrated under reduced pressure, chloroform
  5. additionwas added
  6. washthe mixture was washed succesively with saturated aqueous sodium bicarbonate and 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-ec68c643517b423cb24042cb6442717c
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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