Ethyl Acetate → 1-[5-Chloro-2-(methylsulfonyl)benzyl]-2-imino-5-methyl-1,2-dihydropyridine-3-carboxamide hydrochloride

HRID 1013963Notes

Reaction equation

HRID 1013963 reaction equation
[NH2:1][C:2]1[N:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].Br[CH2:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[S:21]([CH3:24])(=[O:23])=[O:22].C(OCC)(=O)C>CN(C)C=O>[ClH:20].[Cl:20][C:18]1[CH:17]=[CH:16][C:15]([S:21]([CH3:24])(=[O:23])=[O:22])=[C:14]([CH:19]=1)[CH2:13][N:10]1[CH:9]=[C:8]([CH3:11])[CH:7]=[C:3]([C:4]([NH2:6])=[O:5])[C:2]1=[NH:1]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 668775512-(Bromomethyl)-4-chloro-1-(methylsulfonyl)benzeneHCID 668782802-Amino-5-methylnicotinamide

Product 1

HCID 669700871-[5-Chloro-2-(methylsulfonyl)benzyl]-2-imino-5-methyl-1,2-dihydropyridine-3-carboxamide hydrochlorideYield 29.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution (3 ml) of 2-amino-5-methylnicotinamide (100 mg) in N,N-dimethylformamide was added 2-(bromomethyl)-4-chloro-1-(methylsulfonyl)benzene (220 mg), and the mixture was stirred at 100° C. for 4 hr. The mixture was allowed to cool to room temperature, ethyl acetate was added, and the precipitated crystals were collected by filtration. The obtained crystals were dissolved in 1N sodium hydroxide solution, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=5:1→ethyl acetate:methanol=10:1). The obtained yellow solid was dissolved in methanol, 4N hydrogen chloride-ethyl acetate solution (1 ml) was added, and the mixture was crystallized from methanol-ethyl acetate to give the title compound (45 mg).

Workup

  1. temperatureto cool to room temperature
  2. filtrationthe precipitated crystals were collected by filtration
  3. dissolutionThe obtained crystals were dissolved in 1N sodium hydroxide solution
  4. extractionthe solution was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=5:1→ethyl acetate:methanol=10:1)
  9. dissolutionThe obtained yellow solid was dissolved in methanol
  10. addition4N hydrogen chloride-ethyl acetate solution (1 ml) was added
  11. customthe mixture was crystallized from methanol-ethyl acetate

Sources & evidence

ORD record
ord-7ce21ce5d8794bf385b6025b16d90320
Source dataset
uspto-grants-2011_07
Patent number
US07982044B2

Reaction notes

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