Hydrochloric Acid → N-Methyl-4-piperazin-1-yl-pyridine-2-carboxamide hydrochloride

HRID 333979Notes

Reaction equation

HRID 333979 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][CH3:11])=[O:9])[CH:3]=1.[NH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(=O)(O)[O-].[Na+].Cl.O1CCOCC1>C(O)CCC.C(O)C>[ClH:1].[CH3:11][NH:10][C:8]([C:4]1[CH:3]=[C:2]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:7]=[CH:6][N:5]=1)=[O:9]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 4837PiperazineHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 14768144-Chloro-N-methylpicolinamide

Product 1

HCID 66835948N-Methyl-4-piperazin-1-yl-pyridine-2-carboxamide hydrochlorideYield 33.2%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 702EthanolSolvent

Procedure

A mixture of 4-Chloro-N-methyl-pyridine-2-carboxamide (400 mg, 2.345 mmol), piperazine (808 mg, 9.38 mmol) and sodium bicarbonate (591 mg, 7.03 mmol) in 1-butanol (4 ml) was heated under reflux for 18 hours. The mixture was filtered, the filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (silica, 1-5% MeOH—basified with ammonia—in DCM) to give a colourless oil. The oil was dissolved in 2 ml ethanol and 4N HCl in dioxane (1.11 ml, 4.4 mmol) was added. The mixture was stirred for 1 hour at room temperature and filtered. The filter residue was rinsed with DCM and ethanol, dried under reduced pressure to give 200 mg of a white solid (0.779 mmol, 33%). MS (ESI) m/z=221.2 [M+1]+.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 18 hours
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by column chromatography (silica, 1-5% MeOH—basified with ammonia—in DCM)
  6. customto give a colourless oil
  7. filtrationfiltered
  8. washThe filter residue was rinsed with DCM and ethanol
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-e94cb864eb404ae4a129d9471dbda4ba
Source dataset
uspto-grants-2014_11
Patent number
US08883791B2

Reaction notes

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