1-Hydroxybenzotriazole → 1-tert-butylcarbonylmethyl-2-oxo-3-[(2S)-(2-tert-butoxycarbonylamino-3-phenylpropionyl)amino]-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

HRID 1979368Notes

Reaction equation

HRID 1979368 reaction equation
[C:1]([C:5]([CH2:7][N:8]1[C:14]2[CH:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]=2[N:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:11][CH:10]([NH2:26])[C:9]1=[O:27])=[O:6])([CH3:4])([CH3:3])[CH3:2].[C:28]([O:32][C:33]([NH:35][C@H:36]([C:44](O)=[O:45])[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:34])([CH3:31])([CH3:30])[CH3:29].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(N(CC)CC)C>[C:1]([C:5]([CH2:7][N:8]1[C:14]2[CH:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]=2[N:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:11][CH:10]([NH:26][C:44](=[O:45])[C@@H:36]([NH:35][C:33]([O:32][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:34])[CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:9]1=[O:27])=[O:6])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 212019411-tert-butylcarbonylmethyl-2-oxo-3-amino-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 206577841-tert-butylcarbonylmethyl-2-oxo-3-[(2S)-(2-tert-butoxycarbonylamino-3-phenylpropionyl)amino]-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepineYield 101.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Under argon atmosphere, 1-tert-butylcarbonylmethyl-2-oxo-3-amino-5-phenyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (4.75 g) obtained from Step 2 of Example 95 was dissolved in anhydrous N,N-dimethylformamide (40 ml), N-tert-butoxycarbonyl-L-phenylalanine (3.80 g), 1-hydroxybenzotriazole (1.93 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.74 g) and triethylamine (3.65 ml) were added under ice-cooling, the mixture was stirred for 5 minutes at same temperature, and subsequently the resultant mixture was allowed to come to room temperature, stirred for 2 hours. Ice-water was added to the reaction mixture, extracted with ethyl acetate, the organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. 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 8.06 g of the titled compound (Yield: 100%).

Workup

  1. temperaturecooling
  2. customto come to room temperature
  3. stirringstirred for 2 hours
  4. extractionextracted with ethyl acetate
  5. washthe organic layer was washed with 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-6e096b67515543588480fa6bd49ed32a
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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