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

HRID 1979377Notes

Reaction equation

HRID 1979377 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].Cl[C:14](Cl)([O:16]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[C:32]1([CH3:61])[C:33]([C:38]([CH2:40][N:41]2[C:47]3[CH:48]=[C:49]([CH3:52])[CH:50]=[CH:51][C:46]=3[N:45]([C:53](=[O:58])[C:54]([CH3:57])([CH3:56])[CH3:55])[CH2:44][CH:43]([NH2:59])[C:42]2=[O:60])=[O:39])=[CH:34][CH:35]=[CH:36][CH:37]=1>O1CCCC1>[C:32]1([CH3:61])[C:33]([C:38]([CH2:40][N:41]2[C:47]3[CH:48]=[C:49]([CH3:52])[CH:50]=[CH:51][C:46]=3[N:45]([C:53](=[O:58])[C:54]([CH3:55])([CH3:56])[CH3:57])[CH2:44][CH:43]([NH:59][C:14]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([F:12])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:11]=3)=[O:16])[C:42]2=[O:60])=[O:39])=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 15621043Methyl 5-amino-2-fluorobenzoateHCID 212016171-(2-toluoylmethyl)-2-oxo-3-amino-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 212019031-[1-(2-toluoylmethyl)-2-oxo-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-methoxycarbonyl-4-fluorophenyl)ureaYield 188.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Methyl 5-amino-2-fluorobenzoate (241 mg) was dissolved in tetrahydrofuran (43 ml), under ice-cooling triphosgene (142 mg) was added and triethylamine (123 μl) were added five times every 3 minutes, a solution of 1-(2-toluoylmethyl)-2-oxo-3-amino-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (528 mg) in tetrahydrofuran (20 ml) was added thereto, and the mixture was allowed to come to room temperature and stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, water (50 ml) was added, and extracted with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=2:1), to thereby obtain 543 mg of the titled compound (Yield: 69.3%).

Workup

  1. additionwas added
  2. customto come to room temperature
  3. concentrationThe reaction mixture was concentrated under reduced pressure, water (50 ml)
  4. additionwas added
  5. extractionextracted with methylene chloride
  6. washThe organic layer was washed with 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-973222baaf8644d3ad3665d001e2ba0c
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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