Water → 7-bromo-2-(1-methyl-1H-pyrazol-4-yl)quinoxaline

HRID 927314Notes

Reaction equation

HRID 927314 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8](Cl)=[N:9]2)=[CH:4][CH:3]=1.[CH3:13][N:14]1[CH:18]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:16]=[N:15]1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8]([C:17]3[CH:16]=[N:15][N:14]([CH3:13])[CH:18]=3)=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 49132537-Bromo-2-chloroquinoxaline

Product 1

HCID 578432587-bromo-2-(1-methyl-1H-pyrazol-4-yl)quinoxalineYield 82.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Under N2, 7-bromo-2-chloro-quinoxaline (20 g; 82.1 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (17.1 g; 82.1 mmol), 2M sodium carbonate aqueous solution (41.1 mL; 82.1 mmol) in ethylene glycol dimethyl ether (200 mL) were degassed by bubbling nitrogen through for 15 minutes. Tetrakis(triphenylphosphine)palladium (0) (0.95 g; 0.82 mmol) was added and heated at reflux for 15 hours. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was dried over MgSO4, filtered and evaporated to dryness to give 29.9 g. The crude compound was purified by chromatography over silica gel (Irregular SiOH, 20-45 μm, 1000 g MATREX; mobile phase 0.1% NH4OH, 98% DCM, 2% CH3OH). The pure fractions were collected and concentrated till dryness to give 19.5 g (82%) of 7-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-quinoxaline. MP=172° C.

Workup

  1. customby bubbling nitrogen through for 15 minutes
  2. temperatureheated
  3. temperatureat reflux for 15 hours
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customto give 29.9 g
  9. customThe crude compound was purified by chromatography over silica gel (Irregular SiOH, 20-45 μm, 1000 g MATREX; mobile phase 0.1% NH4OH, 98% DCM, 2% CH3OH)
  10. customThe pure fractions were collected
  11. concentrationconcentrated till dryness

Sources & evidence

ORD record
ord-4b91a020adac45cfbb8f9bd48f171b67
Source dataset
uspto-grants-2016_03
Patent number
US09290478B2

Reaction notes

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