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

HRID 1015698Notes

Reaction equation

HRID 1015698 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]=[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=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]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[S:21]([CH3:24])(=[O:23])=[O:22])[CH:9]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 668768832-Amino-5-chloronicotinamideHCID 668775512-(Bromomethyl)-4-chloro-1-(methylsulfonyl)benzene

Product 1

HCID 669700865-Chloro-1-(5-chloro-2-(methylsulfonyl)benzyl)-2-imino-1,2-dihydropyridine-3-carboxamide hydrochlorideYield 11.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(Step 4) A solution of 2-amino-5-chloronicotinamide (210 mg) and 2-(bromomethyl)-4-chloro-1-(methylsulfonyl)benzene obtained in Step 3 (450 mg) in DMF (5 ml) was stirred at 100° C. for 3 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 aqueous sodium hydrogen carbonate 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=1:1→3:1). The obtained yellow solid was dissolved in methanol, and 2N hydrogen chloride-ethyl acetate solution was added. The solvent was evaporated under reduced pressure, and the residue was crystallized from methanol-ethyl acetate to give the title compound (30 mg).

Workup

  1. filtrationthe precipitated crystals were collected by filtration
  2. dissolutionThe obtained crystals were dissolved in aqueous sodium hydrogen carbonate 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=1:1→3:1)
  8. dissolutionThe obtained yellow solid was dissolved in methanol
  9. addition2N hydrogen chloride-ethyl acetate solution was added
  10. customThe solvent was evaporated under reduced pressure
  11. customthe residue was crystallized from methanol-ethyl acetate

Sources & evidence

ORD record
ord-66f20816587040cc8ea510f2bf5c1614
Source dataset
uspto-grants-2011_07
Patent number
US07985862B2

Reaction notes

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