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

HRID 447849Notes

Reaction equation

HRID 447849 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][CH:17]=[CH:16][C:15]=1[S:20]([CH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1)(=[O:22])=[O:21].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][CH:17]=[CH:16][C:15]=2[S:20]([CH:23]2[CH2:24][CH2:25][CH2:26][CH2:27]2)(=[O:22])=[O:21])[CH:9]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 668768832-Amino-5-chloronicotinamideHCID 668777811-(Bromomethyl)-2-(cyclopentylsulfonyl)benzene

Product 1

HCID 669700935-Chloro-1-[2-(cyclopentylsulfonyl)benzyl]-2-imino-1,2-dihydropyridine-3-carboxamide hydrochlorideYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1H NMR (300 MHz, CDCl3) δ ppm 1.59-1.73 (2H, m) 1.77-1.97 (4H, m) 1.99-2.17 (2H, m) 3.84-4.02 (1H, m) 5.07 (2H, s) 7.40-7.54 (1H, m) 7.56-7.67 (2H, m) 8.01 (1H, d, J=7.72 Hz). (Step 4) A solution of 2-amino-5-chloronicotinamide (200 mg) and 1-(bromomethyl)-2-(cyclopentylsulfonyl)benzene obtained in Step 3 (530 mg) in DMF (5 ml) was stirred at 90° C. for 20 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 a mixed solvent of ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried over magnesium sulfate, and filtered. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=3:1). The obtained residue was dissolved in methanol, and 4N hydrogen chloride-ethyl acetate solution (0.5 ml) was added. The mixture was crystallized from methanol-ethyl acetate, and the precipitated crystals were collected by filtration, and recrystallized to give the title compound (70% 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 a mixed solvent of ethyl acetate-tetrahydrofuran
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=3:1)
  9. dissolutionThe obtained residue was dissolved in methanol
  10. addition4N hydrogen chloride-ethyl acetate solution (0.5 ml) was added
  11. customThe mixture was crystallized from methanol-ethyl acetate
  12. filtrationthe precipitated crystals were collected by filtration
  13. customrecrystallized

Sources & evidence

ORD record
ord-b2fb895878b3498182d2493d9ab947b8
Source dataset
uspto-grants-2013_07
Patent number
US08481569B2

Reaction notes

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