1-Hydroxybenzotriazole → 1-tert-butylcarbonylmethyl-2-oxo-3-[(2S)-(2-tert-butoxycarbonylamino-3-phenylpropionyl)amino]-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

HRID 1979324Notes

Reaction equation

HRID 1979324 reaction equation
[C:1]([C:5]([CH2:7][N:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:11][CH:10]([NH2:25])[C:9]1=[O:26])=[O:6])([CH3:4])([CH3:3])[CH3:2].[C:27]([O:31][C:32]([NH:34][C@H:35]([C:43](O)=[O:44])[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:33])([CH3:30])([CH3:29])[CH3:28].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(OCC)(=O)C.O.C(N(CC)CC)C>[C:1]([C:5]([CH2:7][N:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:11][CH:10]([NH:25][C:43](=[O:44])[C@@H:35]([NH:34][C:32]([O:31][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:33])[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:9]1=[O:26])=[O:6])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 212016651-tert-butylcarbonylmethyl-2-oxo-3-amino-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 206577831-tert-butylcarbonylmethyl-2-oxo-3-[(2S)-(2-tert-butoxycarbonylamino-3-phenylpropionyl)amino]-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepineYield 100%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-tert-Butylcarbonylmethyl-2-oxo-3-amino-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (3.62 g) was dissolved in anhydrous N,N-dimethyl formamide (30 ml) under argon atmosphere, N-tert-butoxycarbonyl-L-phenylalanine (3.00 g), 1-hydroxybenzotriazole (1.73 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.17 g) and triethylamine (2.08 g) were added at ice-cooling, thereto the mixture was stirred for 5 minutes under ice-cooling, and stirred at room temperature for one hour. Water and ethyl acetate were added to the reaction mixture, separated, the organic layer was successively washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1), to thereby obtain 6.17 g of the title compound.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringstirred at room temperature for one hour
  4. customseparated
  5. washthe organic layer was successively washed with water 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 (n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-2b61e9fc9c7348b0888268b97ac30625
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

Loading…