Tetrahydrofuran → 1-[1-(2-toluoylmethyl)-2-oxo-5-pivaloyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-[3-(N,N-dimethylamino)phenyl]urea

HRID 1979320Notes

Reaction equation

HRID 1979320 reaction equation
[C:1](N1C=CN=C1)([N:3]1C=CN=C1)=[O:2].[C:13]1([CH3:41])[C:14]([C:19]([CH2:21][N:22]2[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]([C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:25][CH:24]([NH2:39])[C:23]2=[O:40])=[O:20])=[CH:15][CH:16]=[CH:17][CH:18]=1.[CH2:42]([N:44]([CH2:47][CH3:48])[CH2:45]C)C.O1[CH2:53][CH2:52][CH2:51][CH2:50]1>>[C:13]1([CH3:41])[C:14]([C:19]([CH2:21][N:22]2[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]([C:33](=[O:38])[C:34]([CH3:36])([CH3:37])[CH3:35])[CH2:25][CH:24]([NH:39][C:1]([NH:3][C:52]3[CH:51]=[CH:50][CH:48]=[C:47]([N:44]([CH3:42])[CH3:45])[CH:53]=3)=[O:2])[C:23]2=[O:40])=[O:20])=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 212016481-(2-toluoylmethyl)-2-oxo-3-amino-5-pivaloyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212017891-[1-(2-toluoylmethyl)-2-oxo-5-pivaloyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-[3-(N,N-dimethylamino)phenyl]ureaYield 40.3%

Procedure

1,1′-Carbonyldiimidazole (244 mg) was added to a solution of 1-(2-toluoylmethyl)-2-oxo-3-amino-5-pivaloyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (393 mg) in anhydrous tetrahydrofuran (5 ml), stirred for 30 minutes at room temperature,N,N-dimethyl-m-phenylenediamine dihydrochloride (335 mg) and triethylamine (0.67 ml) was added, and the mixture was refluxed overnight. The reaction mixture was concentrated under reduced pressure, appeared insoluble material was removed and purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1). Etanol was added to the residue for crystallization and filtrated, to thereby obtain 224 mg of the title compound (Yield: 40.3%) as white solid.

Workup

  1. additionwas added
  2. temperaturethe mixture was refluxed overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customwas removed
  5. custompurified by silica gel column chromatography (n-hexane:ethyl acetate=1:1)
  6. additionEtanol was added to the residue for crystallization
  7. filtrationfiltrated

Sources & evidence

ORD record
ord-1adb2a6d5a754d88bc4c29a82e6db41b
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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