반응 #2286318

ord-6a7de175e06d4513bf59eee6c17ef0ff

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도was heated
  2. 2
    온도to reflux for 24 h
  3. 3
    세척washed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL)
  4. 4
    추출extracted with ethyl acetate (50 mL)
  5. 5
    건조dried over magnesium sulfate
  6. 6
    여과filtered
  7. 7
    농축concentrated under vacuum
  8. 8
    기타The resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid)
  9. 9
    기타The desired fractions were collected
  10. 10
    농축concentrated
  11. 11
    기타freeze dried
  12. 12
    기타The resulting solid was purified by flash chromatography
  13. 13
    세척eluted with 10% methanol in methylene chloride
  14. 14
    기타The desired fractions were collected
  15. 15
    농축concentrated under vacuum
  16. 16
    기타to afford a solid which
  17. 17
    기타was dried under high vacuum

실험 절차

A mixture of [3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile (55) (assume 0.180 mmol) in concentrated hydrochloric acid (4 mL) was heated to reflux for 24 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (75 mL) and washed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL). The water layers were combined and extracted with ethyl acetate (50 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated under vacuum. The resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid). The desired fractions were collected, concentrated and freeze dried. The resulting solid was purified by flash chromatography using silica gel eluted with 10% methanol in methylene chloride. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford 3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetic acid (56) (8.6 mg, 13% for 2 steps) as a white solid; EI(+)-HRMS m/z calcd for C16H16Cl2N2O3 (M+H)+ 355.0611, found 355.0611. MW=355.2235, Exact Mass=354.0538

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: USRE046024E1uspto-grants-2016_06