反応 #2286318

ord-6a7de175e06d4513bf59eee6c17ef0ff

反応方程式

CC(C)c1cc(Cc2c(Cl)cc(CC#N)cc2Cl)n[nH]c1=O
[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile
CC(C)c1cc(Cc2c(Cl)cc(CC#N)cc2Cl)n[nH]c1=O
[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile
CCOC(C)=O
ethyl acetate
CC(C)c1cc(Cc2c(Cl)cc(CC(=O)O)cc2Cl)n[nH]c1=O
acetic acid
収率 13.0%
CC(C)c1cc(Cc2c(Cl)cc(CC(=O)O)cc2Cl)n[nH]c1=O
[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetic acid
収率 13.0%

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度was heated
  2. 2
    温度to reflux for 24 h
  3. 3
    洗浄washed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL)
  4. 4
    抽出extracted with ethyl acetate (50 mL)
  5. 5
    乾燥dried over magnesium sulfate
  6. 6
    ろ過filtered
  7. 7
    濃縮concentrated under vacuum
  8. 8
    その他The resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid)
  9. 9
    その他The desired fractions were collected
  10. 10
    濃縮concentrated
  11. 11
    その他freeze dried
  12. 12
    その他The resulting solid was purified by flash chromatography
  13. 13
    洗浄eluted with 10% methanol in methylene chloride
  14. 14
    その他The desired fractions were collected
  15. 15
    濃縮concentrated under vacuum
  16. 16
    その他to afford a solid which
  17. 17
    その他was dried under high vacuum

実験手順

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

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: USRE046024E1uspto-grants-2016_06