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

HRID 1979461Notes

Reaction equation

HRID 1979461 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]1([CH3:74])[C:45]([C:50]([CH2:52][N:53]2[C:59]3[CH:60]=[C:61]([CH3:64])[CH:62]=[CH:63][C:58]=3[N:57]([C:65](=[O:71])[CH2:66][C:67]([CH3:70])([CH3:69])[CH3:68])[CH2:56][CH:55]([NH2:72])[C:54]2=[O:73])=[O:51])=[CH:46][CH:47]=[CH:48][CH:49]=1>O1CCOCC1.C(OCC)(=O)C.CCCCCC>[C:44]1([CH3:74])[C:45]([C:50]([CH2:52][N:53]2[C:59]3[CH:60]=[C:61]([CH3:64])[CH:62]=[CH:63][C:58]=3[N:57]([C:65](=[O:71])[CH2:66][C:67]([CH3:69])([CH3:70])[CH3:68])[CH2:56][CH:55]([NH:72][C:23]([NH:20][C:36]3[CH:40]=[CH:41][CH:42]=[C:34]([C:33]([O:32][CH2:25][C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)=[O:43])[CH:35]=3)=[O:8])[C:54]2=[O:73])=[O:51])=[CH:46][CH:47]=[CH:48][CH:49]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 13918608Isophthalic acid benzyl esterHCID 212017651-(2-toluoylmethyl)-2-oxo-3-amino-5-(3,3-dimethylbutanoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 21201912(+)-1-[1-(2-toluoylmethyl)-2-oxo-5-(3,3-dimethylbutanoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-benzyloxycarbonylphenyl)ureaYield 85.2%

Reagents, catalysts & solvents 3

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

Diphenylphosphoryl azide (6.60 g) and triethylamine (3.75 g) were added to a solution of isophthalic acid benzyl ester (5.38 g) in anhydrous dioxane (50 ml), and the mixture was stirred at internal temperature 60° for 30 minutes and stirred at internal temperature 80° for one hour. The reaction mixture was allowed to cool at room temperature,a solution of (+)-1-(2-toluoylmethyl)-2-oxo-3-amino-5-(3,3-dimethylbutanoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (3.0 g) in anhydrous dioxane (50 ml) was added thereto, and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was concentrated under reduced pressure, chloroform (200 ml) was added to the residue, the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography(NH-DM1020, produced by Fujisilicia Co. Ltd., n-hexane:ethyl acetate=2:1), to thereby obtain 4.08 g of the title compound (Yield 85.2%).

Workup

  1. stirringstirred at internal temperature 80° for one hour
  2. stirringthe mixture was stirred at room temperature for 15 minutes
  3. concentrationThe reaction mixture was concentrated under reduced pressure, chloroform (200 ml)
  4. additionwas added to the residue
  5. washthe organic layer was washed with saturated aqueous sodium bicarbonate 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(NH-DM1020
  9. customproduced by Fujisilicia Co

Sources & evidence

ORD record
ord-0c406280a22c4f0999fef2f8fe9d8848
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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