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

HRID 1015704Notes

Reaction equation

HRID 1015704 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[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[C:16]([Cl:24])[CH:15]=1.C(OCC)(=O)C>CN(C=O)C>[ClH:11].[Cl:11][C:8]1[CH:7]=[C:3]([C:4]([NH2:6])=[O:5])[C:2](=[NH:1])[N:10]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[C:16]([Cl:24])[CH:15]=2)[CH:9]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 179665394-(Bromomethyl)-2-chloro-1-(methylsulfonyl)benzeneHCID 668768832-Amino-5-chloronicotinamide

Product 1

HCID 669700645-Chloro-1-[3-chloro-4-(methylsulfonyl)benzyl]-2-imino-1,2-dihydropyridine-3-carboxamide hydrochlorideYield 27.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-amino-5-chloronicotinamide (200 mg) and 4-(bromomethyl)-2-chloro-1-(methylsulfonyl)benzene (430 mg) in DMF (3 ml) 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=9:1→1:0). The obtained yellow solid was dissolved in methanol, 4N hydrogen chloride-ethyl acetate solution was added, and the precipitated crystals were collected by filtration, and recrystallized to give the title compound (65 mg).

Workup

  1. filtrationthe 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=9:1→1:0)
  8. dissolutionThe obtained yellow solid was dissolved in methanol
  9. addition4N hydrogen chloride-ethyl acetate solution was added
  10. filtrationthe precipitated crystals were collected by filtration
  11. customrecrystallized

Sources & evidence

ORD record
ord-9c682f2eccc640c3ab1843a384e87b54
Source dataset
uspto-grants-2011_07
Patent number
US07985862B2

Reaction notes

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