Ethyl Acetate → 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepine

HRID 1485424Notes

Reaction equation

HRID 1485424 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12](C)=[N:13][N:14]=[C:10]3[CH2:9][CH2:8][N:7](C3C=CC(Cl)=CC=3)[C:6]=2[CH:23]=1.CC1(C)C(C)(C)OB(C2C=CC(C(OC)=O)=CC=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>O1CCOCC1.O>[CH:12]1[N:11]2[C:5]3[CH:4]=[CH:3][CH:2]=[CH:23][C:6]=3[N:7]=[CH:8][CH2:9][C:10]2=[N:14][N:13]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2773500Methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 709789288-bromo-6-(4-chlorophenyl)-1-methyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine2×

Product 1

HCID 867185014H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepine,5,6-dihydro-1-methyl-8-bromo-6-(4-chloro-phenyl) (Compound 13; 60 mg, 0.15 mmol), methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (81 mg, 0.30 mmol), and cesium carbonate (98 mg, 0.30 mmol) in dioxane (2 mL) and water (1 mL) was heated at 120° C. for 20 minutes under microwave (pressure: 17.2 bar, equipment power: 150 W). The solid was filtered and the filtrate was concentrated to give a residue. To the residue, ethyl acetate (30 mL) was added and the mixture was washed with brine (20 mL×3). The organic phase was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated to give a residue, which was purified by column chromatography (silica gel, dichloromethane/methanol=10:1) to afford 4H-[1,2,4]Triazolo[4,3-a][1,5]benzodiazepine, 5,6-dihydro-1-methyl-8-(4-carboxy-phenyl)-6-(4-chloro-phenyl) as a white solid (30 mg, 47%).

Workup

  1. filtrationThe solid was filtered
  2. concentrationthe filtrate was concentrated
  3. customto give a residue
  4. washthe mixture was washed with brine (20 mL×3)
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customto give a residue, which
  9. customwas purified by column chromatography (silica gel, dichloromethane/methanol=10:1)

Sources & evidence

ORD record
ord-65acf8f87cc94334828f389aa542fc60
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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