Sodium Carbonate → 5-(5-Chloro-2-methoxyphenyl)imidazo[1,2-a]pyridine

HRID 2203416Notes

Reaction equation

HRID 2203416 reaction equation
[ClH:1].Cl[C:3]1[N:8]2[CH:9]=[CH:10][N:11]=[C:7]2[CH:6]=[CH:5][CH:4]=1.C(=O)([O-])[O-].[Na+].[Na+].O1[CH2:23][CH2:22][O:21][CH2:20]C1>C(OCC)(=O)C.O.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>[Cl:1][C:4]1[CH:5]=[CH:6][C:22]([O:21][CH3:20])=[C:23]([C:3]2[N:8]3[CH:9]=[CH:10][N:11]=[C:7]3[CH:6]=[CH:5][CH:4]=2)[CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 219941745-Chloroimidazo[1,2-a]pyridine hydrochloride

Product 1

HCID 895442625-(5-Chloro-2-methoxyphenyl)imidazo[1,2-a]pyridineYield 70%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 5-chloroimidazo[1,2-a]pyridine hydrochloride (1.89 g, 10.0 mmol), (5-chloro-2-methoxy)benzene boronic acid (2.07 g, 12.0 mmol), 2 M aqueous sodium carbonate (20 mL, 40 mmol) and p-dioxane (50 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.58 g, 0.50 mmol) at ambient temperature. The mixture was heated at reflux for 16 h, allowed to cool to ambient temperature and diluted with ethyl acetate (50 mL) and water (20 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 50-80% gradient of ethyl acetate in hexanes to afford 5-(5-chloro-2-methoxyphenyl)imidazo[1,2-a]pyridine as a colorless solid in 70% yield (1.82 g): 1H NMR (300 MHz, DMSO-d6) δ7.72-7.48 (m, 4H), 7.37-7.23 (m, 3H), 6.89 (d, J=6.6 Hz, 1H), 3.74 (s, 3H); MS (ES+) m/z 259.0 (M+1), 261.0 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 16 h
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluting with a 50-80% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3c864f4a5f4644cdb14002a6f68976d9
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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