Hydrochloric Acid → 7-Phenylimidazo[1,2-a]pyridine

HRID 1245472Notes

Reaction equation

HRID 1245472 reaction equation
C(OC(O[CH2:8][CH3:9])CBr)C.Cl.[C:11]1([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[CH:18]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C([O-])(O)=O.[Na+]>O.O1CCOCC1.CO>[C:11]1([C:17]2[CH:22]=[CH:21][N:20]3[CH:8]=[CH:9][N:23]=[C:19]3[CH:18]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 1090142-Pyridinamine, 4-phenyl-HCID 516892Sodium Bicarbonate

Product 1

HCID 130430307-Phenylimidazo[1,2-a]pyridine

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
23 °C

Procedure

A mixture of bromoacetaldehyde diethyl acetal (0.88 mL, 5.9 mmol, 2.0 equiv) and concentrated HCl (0.1 mL, 0.4 equiv) in water (15 mL) was stirred at 23° C. for 2 h, then heated at 80° C. for 30 min. The mixture was allowed to cool to 23° C., and 4-phenylpyridin-2-amine (1-3, 0.50 g, 2.9 mmol, 1 equiv) and NaHCO3 (0.59 g, 7.1 mmol, 2.4 equiv) were added. The resulting mixture was then heated to 50° C. where MeOH (2 mL) and dioxane (3 mL) were added to increase solubility. The reaction mixture was stirred at 50° C. for 18 h, then concentrated. The residue was partitioned between EtOAc (200 mL) and brine (200 mL). The organic layer was concentrated to provide 7-phenylimidazo[1,2-a]pyridine (1-4) as a brown solid. 1H NMR (300 MHz, CDCl3) δ 8.18 (d, 1H, J=7.3 Hz), 7.84 (s, 1H), 7.67 (s, 1H), 7.66 (s, 2H, J=7.3 Hz), 7.60 (s, 1H), 7.49 (t, 2H, J=7.5 Hz), 7.40 (t, 1H, J=7.3 Hz), 7.09 (dd, 1H, J=7.0, 1.2 Hz).

Workup

  1. temperatureheated at 80° C. for 30 min
  2. temperatureto cool to 23° C.
  3. additionwere added
  4. temperatureto increase solubility
  5. stirringThe reaction mixture was stirred at 50° C. for 18 h
  6. concentrationconcentrated
  7. customThe residue was partitioned between EtOAc (200 mL) and brine (200 mL)
  8. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-673a4cba15d1465cb7f0aeb9a14c5566
Source dataset
uspto-grants-2006_10
Patent number
US07125888B2

Reaction notes

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