Benzyl Chloride → 1-benzyl-4-bromo-2-methyl-1H-benzo[d]imidazole

HRID 82524Notes

Reaction equation

HRID 82524 reaction equation
[CH2:1](Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:9][C:10]1[C:18]2[N:17]=[C:16]([CH3:19])[NH:15][C:14]=2[CH:13]=[CH:12][CH:11]=1.[H-].[Na+]>CN(C=O)C.CO>[CH2:1]([N:15]1[C:14]2[CH:13]=[CH:12][CH:11]=[C:10]([Br:9])[C:18]=2[N:17]=[C:16]1[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 7503Benzyl ChlorideHCID 24758Sodium hydrideHCID 158289794-bromo-2-methyl-1H-1,3-benzodiazole

Product 1

HCID 671269161-benzyl-4-bromo-2-methyl-1H-benzo[d]imidazole

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Benzyl chloride (1.527 mL) was added to a solution of 4-bromo-2-methyl-1H-benzimidazole (1.40 g) and sodium hydride (0.531 g) in DMF (10 mL) at 0° C. The mixture was stirred at room temperature under a dry atmosphere for 1 h. The reaction mixture was diluted with MeOH and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 5%-50% EtOAc in hexane) to give 1-benzyl-4-bromo-2-methyl-1H-benzo[d]imidazole (1.88 g) as tan oil. The mixture of 1-benzyl-4-bromo-2-methyl-1H-benzo[d]imidazole (496 mg), 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (700 mg), Pd(Ph3P)4 (87 mg), sodium carbonate (476 mg) and THF (18 mL)-water (0.90 mL) was heated at 100° C. for 1 h under microwave irradiation. The mixture was poured into water at room temperature and extracted with EtOAc. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 10%-50% EtOAc in hexane) to give 3-[4-(1-benzyl-2-methyl-1H-benzimidazol-4-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (450 mg) as white crystals.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by column chromatography (NH silica gel, eluted with 5%-50% EtOAc in hexane)

Sources & evidence

ORD record
ord-08073f0964a6467c9e786e8880a9c5d3
Source dataset
uspto-grants-2014_09
Patent number
US08846713B2

Reaction notes

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