Sodium Carbonate → 2-(5-bromopyridin-2-yl)-1-phenyl-1H-benzo[d]imidazole

HRID 1755513Notes

Reaction equation

HRID 1755513 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](Cl)=O)=[N:6][CH:7]=1.[C:11]1([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[NH2:24])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.P(Cl)(Cl)(Cl)=O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.O1CCOCC1.O.C(N(CC)CC)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:17]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:24]=2)=[N:6][CH:7]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 68297N-Phenyl-o-phenylenediamineHCID 190907715-Bromo-pyridine-2-carbonyl chloride

Product 1

HCID 668063662-(5-bromopyridin-2-yl)-1-phenyl-1H-benzo[d]imidazoleYield 25%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 5-bromopyridine-2-carbonyl chloride (10.11 g, 46 mmol), N-phenyl-1,2-diaminobenzene (8.46 g, 46 mmol) in anhydrous dichloromethane (DCM) (100 mL), was added triethylamine (TEA) at 0° C. Then the whole was stirred at room temperature (RT) for about 20 hours. The mixture was poured into water, extracted with dichloromethane (100 mL×2). The organic phase was collected, dried over sodium sulfate (Na2SO4), and passed through a pad of silica gel (hexanes/ethyl acetate 4:1). After removal of solvent, a brown oil was obtained, which was dissolved in dioxane (150 mL), phosphoryl chloride (POCl3) (25 mL) was added at 0° C., and the mixture was then heated at about 100° C. under argon overnight. Then the whole was poured into ice (200 g) after being cooled to RT, then neutralized by sodium carbonate (Na2CO3), and extracted with dichloromethane (DCM) (200 mL×2). The organic phase was dried over Na2SO4, absorbed on silica gel, and purified by a silica gel column (hexanes/ethyl acetate 4:1). The desired fraction was collected, concentrated, and reprecipitated with hexanes. After filtration and being washed with methanol, an off-white crystalline solid (Compound 1) was obtained, 4.02 g, with an overall 25% yield.

Workup

  1. extractionextracted with dichloromethane (100 mL×2)
  2. customThe organic phase was collected
  3. dry with materialdried over sodium sulfate (Na2SO4)
  4. customAfter removal of solvent
  5. customa brown oil was obtained
  6. temperaturethe mixture was then heated at about 100° C. under argon overnight
  7. temperatureafter being cooled to RT
  8. extractionextracted with dichloromethane (DCM) (200 mL×2)
  9. dry with materialThe organic phase was dried over Na2SO4
  10. customabsorbed on silica gel
  11. custompurified by a silica gel column (hexanes/ethyl acetate 4:1)
  12. customThe desired fraction was collected
  13. concentrationconcentrated
  14. customreprecipitated with hexanes
  15. filtrationAfter filtration
  16. washbeing washed with methanol

Sources & evidence

ORD record
ord-bf582cb292454f9ea06b16f377cf2174
Source dataset
uspto-grants-2015_10
Patent number
US09172051B2

Reaction notes

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