Ethyl Acetate → 1-[4-Bromo-3-(methylsulfonyl)benzyl]-5-chloro-2-imino-1,2-dihydropyridine-3-carboxamide hydrochloride

HRID 447833Notes

Reaction equation

HRID 447833 reaction equation
[NH2:1][C:2]1[N:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[Br:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19]Br)=[CH:15][C:14]=1[S:21]([CH3:24])(=[O:23])=[O:22].C(OCC)(=O)C>CN(C=O)C>[ClH:11].[Br:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:10]2[CH:9]=[C:8]([Cl:11])[CH:7]=[C:3]([C:4]([NH2:6])=[O:5])[C:2]2=[NH:1])=[CH:15][C:14]=1[S:21]([CH3:24])(=[O:22])=[O:23]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 226192541-Bromo-4-(bromomethyl)-2-(methylsulfonyl)benzeneHCID 668768832-Amino-5-chloronicotinamide

Product 1

HCID 668777801-[4-Bromo-3-(methylsulfonyl)benzyl]-5-chloro-2-imino-1,2-dihydropyridine-3-carboxamide hydrochlorideYield 62.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-amino-5-chloronicotinamide (373 mg) and 1-bromo-4-(bromomethyl)-2-(methylsulfonyl)benzene (1.07 g) in DMF (5 ml) was stirred at 90° C. for 24 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=4:1). The obtained yellow solid was dissolved in methanol, 4N hydrogen chloride-ethyl acetate solution (2 ml) was added, and the precipitated crystals were collected by filtration, and recrystallized to give the title compound (310 mg).

Workup

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

Sources & evidence

ORD record
ord-ecf3a9d1ba194cb290c5176344b497e5
Source dataset
uspto-grants-2013_07
Patent number
US08481569B2

Reaction notes

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