反応 #72022

ord-d22a66624de8480183879bb9ed1d20e3

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度The suspension was heated
  2. 2
    その他at 180° C.
  3. 3
    その他for 30 minutes
  4. 4
    抽出the aqueous layer was extracted with ethyl acetate
  5. 5
    洗浄The organic layer was washed with water and brine
  6. 6
    乾燥dried over anhydrous sodium sulfate
  7. 7
    濃縮concentration under reduced pressure
  8. 8
    その他the residue was purified by silica gel chromatography (
  9. 9
    洗浄elution solvent
  10. 10
    その他hexane/ethyl acetate=1/1, then methanol/ethyl acetate=0/1, 1/9) to obtain 80 mg of the crude title compound
  11. 11
    その他This was further purified by thin layer silica gel chromatography (developing solvent: methanol/dichloromethane=5/95)

実験手順

cis(±)-4-Chloro-N-(3-ethoxypiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxamide hydrochloride obtained in Example (131a) (0.100 g, 0.296 mmol), diisopropylethylamine (0.0568 mL, 0.326 mmol), 2-bromo-1,3,4-thiadiazole (0.0587 g, 0.356 mmol) and cesium carbonate (0.106 g, 0.326 mmol) were suspended in N-methylpyrrolidone (2 mL). The suspension was heated using a microwave reactor at 180° C. for 30 minutes. Ethyl acetate and water were added to the reaction solution, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel chromatography (elution solvent: hexane/ethyl acetate=1/1, then methanol/ethyl acetate=0/1, 1/9) to obtain 80 mg of the crude title compound. This was further purified by thin layer silica gel chromatography (developing solvent: methanol/dichloromethane=5/95) to obtain 43 mg of the title compound as a pale brown solid (36%).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08536197B2uspto-grants-2013_09