تفاعل #68132

ord-b3800d3d4a4d47b5aade6287fe2288ea

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    workup.ADDITIONwere added at room temperature
  2. 2
    درجة الحرارةrefluxed
  3. 3
    درجة الحرارةwith heating for 4 hours
  4. 4
    درجة الحرارةrefluxed
  5. 5
    درجة الحرارةwith heating for 4 hours
  6. 6
    درجة الحرارةrefluxed
  7. 7
    درجة الحرارةwith heating for 9.5 hours
  8. 8
    درجة الحرارةrefluxed
  9. 9
    درجة الحرارةwith heating for 1 hour
  10. 10
    درجة الحرارةrefluxed
  11. 11
    درجة الحرارةwith heating for 8 hours
  12. 12
    درجة الحرارةrefluxed
  13. 13
    درجة الحرارةwith heating for 6 hours
  14. 14
    أخرىthe solvent was removed under reduced pressure
  15. 15
    workup.ADDITIONwas added
  16. 16
    أخرىThe organic layer was separated
  17. 17
    استخلاصthe aqueous layer was extracted with chloroform
  18. 18
    غسيلwashed with aqueous saturated sodium chloride solution
  19. 19
    تجفيفdried over anhydrous magnesium sulfate
  20. 20
    أخرىthe solvent was removed under reduced pressure
  21. 21
    أخرىTo the residue thus obtained
  22. 22
    ترشيحthe resulting solid was filtered

الإجراء التجريبي

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.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08524738B2uspto-grants-2013_09