3-Carbethoxy-2-piperidone → ethyl 3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylate

HRID 1398211Notes

Reaction equation

HRID 1398211 reaction equation
O=[C:2]1[CH:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:5][CH2:4][NH:3]1.F[B-](F)(F)F.C[O+](C)C.[CH3:22][O:23][C:24]1[N:29]=[C:28]([C:30]([NH:32][NH2:33])=O)[CH:27]=[CH:26][C:25]=1[N:34]1[CH:38]=[C:37]([CH3:39])[N:36]=[CH:35]1>C(#N)C>[CH3:22][O:23][C:24]1[N:29]=[C:28]([C:30]2[N:3]3[CH2:4][CH2:5][CH2:6][CH:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:2]3=[N:33][N:32]=2)[CH:27]=[CH:26][C:25]=1[N:34]1[CH:38]=[C:37]([CH3:39])[N:36]=[CH:35]1

Participants

5

Reactant 3

HCID 977733-Carbethoxy-2-piperidoneHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 666083826-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridine-2-carbohydrazide

Product 1

HCID 66607844ethyl 3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylateYield 40.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of ethyl 2-oxopiperidine-3-carboxylate (3.5 g) in acetonitrile (100 mL) was added trimethyloxonium tetrafluoroborate (3.0 g) at room temperature, and the mixture was stirred at room temperature for 2 hr. 6-Methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridine-2-carbohydrazide (5.0 g) was added to the reaction mixture at room temperature, and the solvent was evaporated under reduced pressure. Methanol (100 mL) was added to the residue at room temperature, and the mixture was stirred for 2 hr under reflux. The solvent in the reaction mixture was evaporated under reduced pressure, acetonitrile (100 mL) was added to the residue at room temperature, and the mixture was stirred at 80° C. overnight. The solvent in the reaction mixture was evaporated under reduced pressure, the residue was diluted with ethyl acetate and saturated aqueous sodium hydrogen carbonate solution, the mixture was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue of another lot synthesized similarly was combined, and the mixture was purified by silica gel column chromatography (methanol/ethyl acetate) to give the title compound (3.1 g).

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. additionMethanol (100 mL) was added to the residue at room temperature
  3. stirringthe mixture was stirred for 2 hr
  4. temperatureunder reflux
  5. customThe solvent in the reaction mixture was evaporated under reduced pressure, acetonitrile (100 mL)
  6. additionwas added to the residue at room temperature
  7. stirringthe mixture was stirred at 80° C. overnight
  8. customThe solvent in the reaction mixture was evaporated under reduced pressure
  9. additionthe residue was diluted with ethyl acetate and saturated aqueous sodium hydrogen carbonate solution
  10. washthe mixture was washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe residue of another lot synthesized similarly
  14. customthe mixture was purified by silica gel column chromatography (methanol/ethyl acetate)

Sources & evidence

ORD record
ord-a64c52e6d5234a319b4205f27dfb8a56
Source dataset
uspto-grants-2014_12
Patent number
US08901309B2

Reaction notes

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