Potassium Carbonate → Ethyl 2-methylpyrazolo[1,5-a]pyridine-3-carboxylate

HRID 2282169Notes

Reaction equation

HRID 2282169 reaction equation
[I-].[NH2:2][N+:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:9]([O:14][CH2:15][CH3:16])(=[O:13])[C:10]#[C:11][CH3:12].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O.C(OCC)(=O)C.CCCCCC>[CH3:12][C:11]1[C:10]([C:9]([O:14][CH2:15][CH3:16])=[O:13])=[C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][N:3]2[N:2]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 78043Ethyl 2-butynoateHCID 2733704Pyridinium, 1-amino-, iodide (1:1)

Product 1

HCID 12872285Ethyl 2-methylpyrazolo[1,5-a]pyridine-3-carboxylateYield 36,724.199%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 1-aminopyridinium iodide (125 g, 0.56 mmol) in N,N-dimethylformamide (1.2 L) were added ethyl 2-butynoate (54.0 g, 0.48 mmol) and potassium carbonate (79 g, 0.36 mmol) and the mixture was stirred at room temperature for 3 days. The reaction mixture was diluted with water (500 mL), ethyl acetate (500 mL) and hexane (500 mL), and the precipitated solid was collected by filtration, and washed with water (500 mL). The filtrate was extracted with a mixed solvent (1.5 L×2) of ethyl acetate/hexane (1:1) and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The residue obtained by concentration of the filtrate and the solid collected by filtration in the above were combined, washed with diethyl ether (25 mL) and hexane (25 mL) and dried to give the title compound (36.0 g, 37%) as a white solid. The washing solution was concentrated, and the obtained residue was washed with diethyl ether (10 mL) and hexane (10 mL) and dried to give a second crop (11.0 g, 11%) of the title compound as a white solid. The washing solution of the second crop was concentrated, and the obtained residue was purified using a pad (elution solvent: ethyl acetate/hexane=1/1) with silica gel and activated carbon in 2 layers, washed with diethyl ether (5.0 mL) and hexane (5.0 mL) and dried to give a third crop (6.5 g, 7%) of the title compound as a white solid (total yield 55%).

Workup

  1. filtrationthe precipitated solid was collected by filtration
  2. washwashed with water (500 mL)
  3. extractionThe filtrate was extracted with a mixed solvent (1.5 L×2) of ethyl acetate/hexane (1:1)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationthe insoluble material was filtered off
  6. customThe residue obtained by concentration of the filtrate
  7. filtrationthe solid collected by filtration in the
  8. washwashed with diethyl ether (25 mL) and hexane (25 mL)
  9. customdried

Sources & evidence

ORD record
ord-d03a85d06a65490c9abe8c47b0edcdcd
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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