Triethylamine → 1-[1-(2-thenoylmethyl)-2-oxo-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea

HRID 1979350Notes

Reaction equation

HRID 1979350 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:14](Cl)([O:16]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[C:32]1([C:37]([CH2:39][N:40]2[C:46]3[CH:47]=[C:48]([CH3:51])[CH:49]=[CH:50][C:45]=3[N:44]([C:52](=[O:57])[C:53]([CH3:56])([CH3:55])[CH3:54])[CH2:43][CH:42]([NH2:58])[C:41]2=[O:59])=[O:38])[S:36][CH:35]=[CH:34][CH:33]=1>O1CCCC1.O>[C:32]1([C:37]([CH2:39][N:40]2[C:46]3[CH:47]=[C:48]([CH3:51])[CH:49]=[CH:50][C:45]=3[N:44]([C:52](=[O:57])[C:53]([CH3:54])([CH3:55])[CH3:56])[CH2:43][CH:42]([NH:58][C:14]([NH:1][C:2]3[CH:12]=[CH:11][CH:10]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH:3]=3)=[O:16])[C:41]2=[O:59])=[O:38])[S:36][CH:35]=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11400Ethyl 3-aminobenzoateHCID 94429TriphosgeneHCID 212016181-(2-thenoylmethyl)-2-oxo-3-amino-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212015731-[1-(2-thenoylmethyl)-2-oxo-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)ureaYield 234.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl 3-aminobenzoate (0.23 g) was dissolved in tetrahydrofuran (10 ml), and the solution was cooled on ice-water. Triphosgene (0.15 g) was added thereto at internal temperature 7° C., triethylamine (0.53 g) was added dropwise thereto over 10 minutes period, the mixture was allowed to come to room temperature, and stirred for 10 minutes. Subsequently, a suspension of 1-(2-thenoylmethyl)-2-oxo-3-amino-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (0.52 g) in tetrahydrofuran (10 ml ) was added, and the resultant mixture was stirred for one hour. Water was added to the reaction mixture, extracted with methylene chloride, the organic layer was successively washed with water 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 0.70 g of the titled compound as white crystals (Yield: 88%).

Workup

  1. temperaturethe solution was cooled on ice-water
  2. customto come to room temperature
  3. additionwas added
  4. extractionextracted with methylene chloride
  5. washthe organic layer was successively washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-b76022706d674067abff448c7cd64563
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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