反応 #68132

ord-b3800d3d4a4d47b5aade6287fe2288ea

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    workup.ADDITIONwere added at room temperature
  2. 2
    温度refluxed
  3. 3
    温度with heating for 4 hours
  4. 4
    温度refluxed
  5. 5
    温度with heating for 4 hours
  6. 6
    温度refluxed
  7. 7
    温度with heating for 9.5 hours
  8. 8
    温度refluxed
  9. 9
    温度with heating for 1 hour
  10. 10
    温度refluxed
  11. 11
    温度with heating for 8 hours
  12. 12
    温度refluxed
  13. 13
    温度with heating for 6 hours
  14. 14
    その他the solvent was removed under reduced pressure
  15. 15
    workup.ADDITIONwas added
  16. 16
    その他The organic layer was separated
  17. 17
    抽出the aqueous layer was extracted with chloroform
  18. 18
    洗浄washed with aqueous saturated sodium chloride solution
  19. 19
    乾燥dried over anhydrous magnesium sulfate
  20. 20
    その他the solvent was removed under reduced pressure
  21. 21
    その他To the residue thus obtained
  22. 22
    ろ過the resulting solid was filtered

実験手順

To 1 mL of a 1,4-dioxane solution containing 30 mg of 4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)-1-(2-(7-methoxy-4-methyl-2-oxoquinolin-1(2H)-yl)ethyl)cyclohexanecarbonitrile, 1 mL of 20% aqueous potassium hydroxide solution and 1 mL of ethanol were added at room temperature and refluxed with heating for 4 hours. Further, 1 mL of 20% aqueous potassium hydroxide solution was added and refluxed with heating for 4 hours, thereafter 1.5 mL of 20% aqueous potassium hydroxide solution was further added and refluxed with heating for 9.5 hours. After 1 mL of 20% aqueous potassium hydroxide solution and 0.5 mL of ethanol were added and refluxed with heating for 1 hour, further 1 mL of 20% aqueous potassium hydroxide solution was added and refluxed with heating for 8 hours. After 1 mL of 20% aqueous potassium hydroxide solution was added and refluxed with heating for 6 hours, the reaction mixture was cooled to the room temperature, the solvent was removed under reduced pressure. The residue was adjusted to pH 11 with 2.0 mol/L hydrochloric acid and chloroform was added. The organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and extracts were combined, washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. To the residue thus obtained, diethyl ether was added, and the resulting solid was filtered to give 21 mg of 4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)-1-(2-(7-methoxy-4-methyl-2-oxoquinolin-1(2H)-yl)ethyl)cyclohexanecarboxamide as a white solid.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08524738B2uspto-grants-2013_09