Sodium Carbonate → 4-(3-Phenylimidazo[1,2-a]pyridin-7-yl)benzaldehyde

HRID 1245478Notes

Reaction equation

HRID 1245478 reaction equation
I[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]3[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=3)=[CH:10][C:5]2=[N:4][CH:3]=1.[C:19]1(B(O)O)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+]>O1CCOCC1>[C:19]1([C:2]2[N:6]3[CH:7]=[CH:8][C:9]([C:11]4[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=4)=[CH:10][C:5]3=[N:4][CH:3]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 10340Sodium Carbonate2×HCID 66827Phenylboronic Acid2×HCID 433294Lithium ChlorideHCID 219128644-(3-Iodoimidazo[1,2-a]pyridin-7-yl)benzaldehyde

Product 1

HCID 219128614-(3-Phenylimidazo[1,2-a]pyridin-7-yl)benzaldehyde

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Tetrakis(triphenylphosphoine)palladium(0) (92 mg, 0.080 mmol, 0.050 equiv) was added to a deoxygenated mixture of 4-(3-iodoimidazo[1,2-a]pyridin-7-yl)benzaldehyde (2-4, 555 mg, 1.94 mmol, 1 equiv), phenyl boronic acid (486 mg, 3.99 mmol, 2.50 equiv), and aqueous saturated sodium carbonate solution (2.4 mL, 3.0 equiv) in dioxane (20 mL), and the resulting mixture was heated at reflux for 4 h. Additional tetrakis(triphenylphosphoine)palladium(0) (100 mg, 0.09 mmol, 0.05 equiv), phenyl boronic acid (500 mg, 4.0 mmol, 2.5 equiv), aqueous saturated sodium carbonate solution (2.5 mL, 3.1 equiv), and lithium chloride (200 mg, 5 mmol, 3 equiv) were added and the mixture was heated at reflux for 18 h. The reaction mixture was cooled, then concentrated, and the residue was partitioned between half-saturated aqueous NaCl solution (100 mL) and EtOAc (6×100 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by reverse-phase liquid chromotography (H2O/CH3CN gradient w/0.1% TFA) to give 4-(3-phenylimidazo[1,2-a]pyridin-7-yl)benzaldehyde (2-5) as a tan solid. LRMS m/z (M+H) Calcd 299.3, found 298.9.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 4 h
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 18 h
  5. temperatureThe reaction mixture was cooled
  6. concentrationconcentrated
  7. customthe residue was partitioned between half-saturated aqueous NaCl solution (100 mL) and EtOAc (6×100 mL)
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by reverse-phase liquid chromotography (H2O/CH3CN gradient w/0.1% TFA)

Sources & evidence

ORD record
ord-98944097f0ca4bb890d50fa2fdc49477
Source dataset
uspto-grants-2006_10
Patent number
US07125888B2

Reaction notes

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