2-Aminopyridine → Imidazo(1,2-a)pyridine-3-carboxylic acid, 2-methyl-

HRID 2282208Notes

Reaction equation

HRID 2282208 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].Cl[CH:9]([C:15](=O)[CH3:16])[C:10]([O:12]CC)=[O:11]>C(O)C>[CH3:16][C:15]1[N:7]=[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]2[C:9]=1[C:10]([OH:12])=[O:11]

Participants

4

Reactant 2

HCID 104392-AminopyridineHCID 11858Ethyl 2-chloroacetoacetate

Product 1

HCID 89054Imidazo(1,2-a)pyridine-3-carboxylic acid, 2-methyl-Yield 44.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of pyridin-2-amine (10 g, 106 mmol), ethyl 2-chloro-3-oxobutanoate (16 g, 97 mmol) and ethanol (200 mL) was stirred at 80° C. for 2 days. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium bicarbonate solution was added to the obtained residue, and the mixture was extracted with ethyl acetate. The collected organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, 8N aqueous sodium hydroxide solution (25 mL), water (75 mL) and ethanol (200 mL) were added to the obtained residue, and the mixture was stirred at 70° C. for 1 hr. 6N Hydrochloric acid (34 mL) was added dropwise to the reaction mixture under ice-cooling. The resulting precipitate was collected by filtration, washed with water, ethanol and diethyl ether and dried to give the title compound (7.6 g, 44%) as a pale-pink solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium bicarbonate solution
  2. additionwas added to the obtained residue
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe collected organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationthe insoluble material was filtered off
  7. concentrationThe filtrate was concentrated under reduced pressure, 8N aqueous sodium hydroxide solution (25 mL), water (75 mL) and ethanol (200 mL)
  8. additionwere added to the obtained residue
  9. stirringthe mixture was stirred at 70° C. for 1 hr
  10. addition6N Hydrochloric acid (34 mL) was added dropwise to the reaction mixture under ice-
  11. temperaturecooling
  12. filtrationThe resulting precipitate was collected by filtration
  13. washwashed with water, ethanol and diethyl ether
  14. customdried

Sources & evidence

ORD record
ord-4f2e85f486fd4742b91cf0e3aecacda0
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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