Potassium Carbonate → 1-Methyl-1H-pyrazolo[4,3-b]pyridine

HRID 2205287Notes

Reaction equation

HRID 2205287 reaction equation
Br[C:2]1[C:3]([CH:8]=[N:9][NH:10][CH3:11])=[N:4][CH:5]=[CH:6][CH:7]=1.CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O.[Cl-].[NH4+].C(OCC)(=O)C.[Cu]I>[CH3:11][N:10]1[C:2]2[C:3](=[N:4][CH:5]=[CH:6][CH:7]=2)[CH:8]=[N:9]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 117696427HCID 117696427, compound

Product 1

HCID 569722961-Methyl-1H-pyrazolo[4,3-b]pyridineYield 16.4%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
120 °C

Procedure

N-[1-(3-Bromo-pyridin-2-yl)-methylidene]-N′-methyl-hydrazine (5.7 g, 26.63 mmol), copper (I) iodide (507 mg, 2.66 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (76 mg, 0.533 mmol) and potassium carbonate (7.36 g, 53.25 mmol) are suspended in 1-methyl-2-pyrrolidinone (20 mL) and heated at 120° C. for 3 h. The mixture is diluted with saturated ammonium chloride solution and ethyl acetate. The resulting emulsion is filtered, the phases separated and the organic phase washed with brine, dried and volatiles evaporated under reduced pressure. The residue is redissolved in ethyl ether, washed with brine and the solvent removed. The residue is purified by flash chromatography (0-60% EtOAc in cyclohexane) to give 1-methyl-1H-pyrazolo[4,3-b]pyridine (580 mg, content 85%, 14%)

Workup

  1. filtrationThe resulting emulsion is filtered
  2. customthe phases separated
  3. washthe organic phase washed with brine
  4. customdried
  5. customvolatiles evaporated under reduced pressure
  6. dissolutionThe residue is redissolved in ethyl ether
  7. washwashed with brine
  8. customthe solvent removed
  9. customThe residue is purified by flash chromatography (0-60% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-4ddd3f5ba1bf422c8de5cf9678ef3579
Source dataset
uspto-grants-2016_06
Patent number
US09371282B2

Reaction notes

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