Reaktion #643452

ord-39b030a3abd3409c8c42d9c26394ad81

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    workup.STIRRINGAfter being stirred at room temperature for 5 minutes, to the reaction mixture
  2. 2
    workup.STIRRINGThe reaction mixture is stirred at 60□C for 6 hours
  3. 3
    Waschenwashed with 2×8 mL of water
  4. 4
    EinengenAfter concentration
  5. 5
    Sonstigethe crude product is purified by chromatography (heptanes 60%, EtOAc 40%)

Vorschrift

To a solution of [(S)-1-(6-bromo-2-oxo-1,2-dihydro-pyridin-3-ylcarbamoyl)-ethyl]-methyl-carbamic acid benzyl ester (1C) (100 mg, 0.25 mmol) in dimethoxylethane (DME) (3 mL) at room temperature, is added lithium iodide (36 mg, 0.27 mmol) in one portion. After being stirred at room temperature for 5 minutes, to the reaction mixture, is added 4-fluoro-phenyl-(5-chloromethyl-pyridin-3-yl)-methanone (IF) (80 mg, 0.32 mmol) in one portion. After being stirred at room temperature for 5 minutes, to the reaction mixture, is added drop wise diisopropylethylamine (DIPEA) (0.09 mL, 0.50 mmol). The reaction mixture is stirred at 60□C for 6 hours. The reaction solution is diluted with ethyl acetate (EtOAc) (30 mL) and washed with 2×8 mL of water. After concentration, the crude product is purified by chromatography (heptanes 60%, EtOAc 40%) to give ((S)-1-{6-bromo-1-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-2-oxo-1,2-dihydro-pyridin-3-ylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester (1D) (95.7 mg, yield 63%) as light yellow solid, MS (ESI) m/e 621.2, 623.3 (M+H+).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08058272B2uspto-grants-2011_11