Triethylamine → 1-[1-(2-toluoylmethyl)-2-oxo-5-(2-thenoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-tert-butoxycarbonylphenyl)urea

HRID 1979456Notes

Reaction equation

HRID 1979456 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].Cl[C:16](Cl)([O:18]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[C:34]1([CH3:64])[C:35]([C:40]([CH2:42][N:43]2[C:49]3[CH:50]=[C:51]([CH3:54])[CH:52]=[CH:53][C:48]=3[N:47]([C:55](=[O:61])[C:56]3[S:60][CH:59]=[CH:58][CH:57]=3)[CH2:46][CH:45]([NH2:62])[C:44]2=[O:63])=[O:41])=[CH:36][CH:37]=[CH:38][CH:39]=1>O1CCCC1>[C:34]1([CH3:64])[C:35]([C:40]([CH2:42][N:43]2[C:49]3[CH:50]=[C:51]([CH3:54])[CH:52]=[CH:53][C:48]=3[N:47]([C:55](=[O:61])[C:56]3[S:60][CH:59]=[CH:58][CH:57]=3)[CH2:46][CH:45]([NH:62][C:16]([NH:1][C:2]3[CH:14]=[CH:13][CH:12]=[C:4]([C:5]([O:7][C:8]([CH3:10])([CH3:11])[CH3:9])=[O:6])[CH:3]=3)=[O:18])[C:44]2=[O:63])=[O:41])=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 2737408tert-Butyl-3-aminobenzoateHCID 212017831-(2-toluoylmethyl)-2-oxo-3-amino-5-(2-thenoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212016271-[1-(2-toluoylmethyl)-2-oxo-5-(2-thenoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-tert-butoxycarbonylphenyl)ureaYield 249.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Tert-butyl 3-aminobenzoate (1.09 g) was dissolved in tetrahydrofuran (20 ml), triphosgene (0.61 g) was added to a solution under ice-cooling. Subsequently, under ice-cooling triethylamine (2.12 g) was added dropwise, and the mixture was stirred at room temperature for one hour. A solution of 1-(2-toluoylmethyl)-2-oxo-3-amino-5-(2-thenoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (2.23 g) in tetrahydrofuran (20 ml) was added to the mixture, stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid was added to the residue and extracted with chloroform. The organic layer was washed with water, saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=1:1), to thereby obtain 3.35 g of the title compound as colorless amorphous (Yield: 100%).

Workup

  1. temperaturecooling
  2. additionwas added dropwise
  3. stirringstirred at room temperature for one hour
  4. concentrationThe reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid
  5. additionwas added to the residue
  6. extractionextracted with chloroform
  7. washThe organic layer was washed with water, saturated aqueous sodium bicarbonate and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-e32653f8439c4f6e8593e64debc013c3
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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