2-Amino-5-methylpyridine → (6-Methylimidazo[1,2-a]pyridin-2-yl)phenylmethanone

HRID 600614Notes

Reaction equation

HRID 600614 reaction equation
Br[CH2:2][C:3](=O)[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][N:15]=1>CO>[CH3:20][C:17]1[CH:18]=[CH:19][C:14]2[N:15]([CH:2]=[C:3]([C:4]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)=[O:5])[N:13]=2)[CH:16]=1

Participants

4

Reactant 2

HCID 153482-Amino-5-methylpyridineHCID 125689113-Bromo-1-phenylpropane-1,2-dione

Product 1

HCID 24768843(6-Methylimidazo[1,2-a]pyridin-2-yl)phenylmethanoneYield 30.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
4 °C

Procedure

To a solution of 454 mg of 3-bromo-1-phenylpropane-1,2-dione in 1 mL of methanol is added dropwise at 4° C. a solution of 179 mg of 2-amino-5-methylpyridine in 4 mL of methanol. The reaction mixture is stirred for 15 hours at 4° C. and then refluxed for 2 hours. After evaporating off the solvent under reduced pressure, the residue is taken up in dichloromethane and basified with normal sodium hydroxide solution. The basic aqueous phase is extracted with dichloromethane and the combined organic phases are washed with water and then with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The residue is chromatographed on a cartridge of 20 g of silica, eluting with an 85/15 and then 65/35 mixture of cyclohexane and ethyl acetate. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure to give 120 mg of (6-methylimidazo[1,2-a]pyridin-2-yl)phenylmethanone in the form of a beige-colored solid.

Workup

  1. temperaturerefluxed for 2 hours
  2. customAfter evaporating off the solvent under reduced pressure
  3. extractionThe basic aqueous phase is extracted with dichloromethane
  4. washthe combined organic phases are washed with water
  5. dry with materialwith saturated sodium chloride solution, dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe residue is chromatographed on a cartridge of 20 g of silica
  9. washeluting with an 85/15
  10. addition65/35 mixture of cyclohexane and ethyl acetate
  11. additionThe fractions containing the expected product
  12. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-750dd3e7e63c42fbaf10280430831b42
Source dataset
uspto-grants-2011_03
Patent number
US07902219B2

Reaction notes

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