5-Bromo-1-methyl-1H-imidazole → 1-Methylimidazole

HRID 627504Notes

Reaction equation

HRID 627504 reaction equation
C([Mg]Br)C.Br[C:6]1[N:10]([CH3:11])[CH:9]=[N:8][CH:7]=1.CON(C)[C:15]([C:17]1[CH:22]=[CH:21][N:20]=[N:19][CH:18]=1)=[O:16]>C(Cl)Cl>[CH3:11][N:10]1[C:6]([C:15]([C:17]2[CH:22]=[CH:21][N:20]=[N:19][CH:18]=2)=[O:16])=[CH:7][N:8]=[CH:9]1.[CH3:11][N:10]1[CH:6]=[CH:7][N:8]=[CH:9]1

Participants

6

Reactant 3

HCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 59574572N-Methoxy-N-methylpyridazine-4-carboxamideHCID 178418443HCID 178418443, compound

Product 2

HCID 13901-MethylimidazoleHCID 86716077HCID 86716077, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethylmagnesium bromide (3 M in Et2O, 1.04 mL, 3.11 mmol) was added dropwise to a solution of 5-bromo-1-methyl-1H-imidazole (500 mg, 3.11 mmol) in DCM (6 mL) under a nitrogen atmosphere. The mixture was stirred at room temperature 15 min, then was cooled in an ice bath prior to addition of N-methoxy-N-methylpyridazine-4-carboxamide (419 mg, 2.51 mmol, Intermediate 29, step a). The resulting suspension was stirred at room temperature for 2 hours. The reaction was quenched by addition of saturated aqueous NH4Cl, diluted with water, and extracted three times with EtOAc. The aqueous phase was saturated with NaCl and back-extracted with DCM (three times). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, gradient 30-100% CH3CN-DCM, followed by isocratic 5% MeOH-acetone), affording title compound contaminated with 1-methyl-1H-imidazole, the mixture of which was used in the next reaction without further purification.

Workup

  1. temperaturewas cooled in an ice bath
  2. stirringThe resulting suspension was stirred at room temperature for 2 hours
  3. customThe reaction was quenched by addition of saturated aqueous NH4Cl
  4. additiondiluted with water
  5. extractionextracted three times with EtOAc
  6. extractionback-extracted with DCM (three times)
  7. dry with materialThe organic phase was dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash column chromatography (silica gel, gradient 30-100% CH3CN-DCM, followed by isocratic 5% MeOH-acetone)

Sources & evidence

ORD record
ord-faf3037deb1646378b1f2e652554a902
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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