반응 #170215

ord-e804a1ab53e341f5bfef05a2426c4de4

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타then partitioned between ethyl acetate (20 mL) and water (30 mL)
  2. 2
    기타The aqueous layer was separated
  3. 3
    추출successively extracted with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL)
  4. 4
    세척The combined organic phases were washed with a saturated solution of sodium chloride (3×30 mL)
  5. 5
    건조dried over sodium sulfate
  6. 6
    여과filtered
  7. 7
    농축concentrated to dryness
  8. 8
    기타The residue was purified by chromatography on silica gel
  9. 9
    기타The residue was triturated in pentane

실험 절차

3-(Thiophen-2-ylmethoxy)-azetidine hydrochloride (127 mg, 0.62 mmol), EDCI (120 mg, 0.62 mmol), HOBt (86 mg, 0.62 mmol) and diisopropylethylamine (180 μL, 1.03 mmol) were successively added to a solution of (E)-3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)acrylic acid hydrochloride (100 mg, 0.41 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight then partitioned between ethyl acetate (20 mL) and water (30 mL). The aqueous layer was separated and successively extracted with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×30 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (98:2 to 93:7) as eluent. The residue was triturated in pentane to afford the title product as a pale orange solid (21 mg, 14%).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08846711B2uspto-grants-2014_09