Benzimidazole → 2-(Benzimidazol-1-yl)-4-chloro-5-bromopyrimidine

HRID 429286Notes

Reaction equation

HRID 429286 reaction equation
[H-].[Na+].[N:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5][CH:4]=1.[Cl:12][C:13]1[N:18]=[C:17]([Cl:19])[C:16]([Br:20])=[CH:15][N:14]=1>CN(C=O)C.CCOC(C)=O>[Cl:12][C:13]1[N:18]=[C:17]([N:3]2[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[N:5]=[CH:4]2)[C:16]([Br:20])=[CH:15][N:14]=1.[N:3]1([C:13]2[N:18]=[C:17]([Cl:19])[C:16]([Br:20])=[CH:15][N:14]=2)[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[CH:4]1

Participants

7

Reactant 3

HCID 5798BenzimidazoleHCID 24758Sodium hydrideHCID 2899735-Bromo-2,4-dichloropyrimidine

Product 2

HCID 183543922-(Benzimidazol-1-yl)-4-chloro-5-bromopyrimidineHCID 22731922HCID 22731922, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of NaH (23 mg) in 1.5 mL of DMF was added benzimidazole (111 mg). After gas evolution ceased, the mixture was stirred at room temperature for 10 min, then added to a solution of 2,4-dichloro-5-bromopyrimidine (178 mg) in 1 mL of DMF. The mixture was stirred for 3 h at room temperature, then diluted with 10 mL of EtOAc and quenched with 5 mL of water. The phases were separated and the organic phase was washed with 5 mL of water and 5 mL of brine, then dried over Na2SO4 and concentrated. The residue was purified by flash chromatography, eluting with 4:1 hexanes-acetone to provide 151 mg of the title compound (polar isomer) and 15 mg of the regioisomer 2-(benzimidazol-1-yl)-4-chloro-5-bromopyrimidine (nonpolar isomer). Mass spectrum (ESI) 310.9 (M+1).

Workup

  1. stirringThe mixture was stirred for 3 h at room temperature
  2. customquenched with 5 mL of water
  3. customThe phases were separated
  4. washthe organic phase was washed with 5 mL of water and 5 mL of brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography
  8. washeluting with 4:1 hexanes-acetone

Sources & evidence

ORD record
ord-c6daac7d60384014849b46a1eae44d98
Source dataset
uspto-grants-2001_11
Patent number
US06316444B1

Reaction notes

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