Ethyl Acetate → [3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetic acid

HRID 271189Notes

Reaction equation

HRID 271189 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](CC#N)[CH:5]=[C:6]([Cl:19])[C:7]=1[CH2:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[NH:11][N:10]=1.[C:23]([O:26]CC)(=[O:25])[CH3:24]>Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:24][C:23]([OH:26])=[O:25])[CH:5]=[C:6]([Cl:19])[C:7]=1[CH2:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:16])[CH3:17])[C:12](=[O:18])[NH:11][N:10]=1

Participants

4

Reactant 2

HCID 8857Ethyl AcetateHCID 59834478[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile

Product 1

HCID 15981272[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetic acidYield 13%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

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

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 24 h
  3. washwashed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL)
  4. extractionextracted with ethyl acetate (50 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid)
  9. customThe desired fractions were collected
  10. concentrationconcentrated
  11. customfreeze dried
  12. customThe resulting solid was purified by flash chromatography
  13. washeluted with 10% methanol in methylene chloride
  14. customThe desired fractions were collected
  15. concentrationconcentrated under vacuum
  16. customto afford a solid which
  17. customwas dried under high vacuum

Sources & evidence

ORD record
ord-8f6cd58e7f9c49b3b854cb28db58302d
Source dataset
uspto-grants-2008_11
Patent number
US07452882B2

Reaction notes

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