Hydrochloric Acid → 6-(2,6-Dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one

HRID 2199142Notes

Reaction equation

HRID 2199142 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([CH:8]([C:11]2[C:16]([Br:17])=[CH:15][C:14]([CH2:18]OC3CCCCO3)=[CH:13][C:12]=2[Br:26])C#N)=[CH:4][C:3]=1[CH:27]([CH3:29])[CH3:28].C([O-])(=[O:32])C.[Na+].[ClH:35]>C(O)(=O)C.C(OCC)(=O)C>[Br:26][C:12]1[CH:13]=[C:14]([CH2:18][Cl:35])[CH:15]=[C:16]([Br:17])[C:11]=1[CH2:8][C:5]1[CH:4]=[C:3]([CH:27]([CH3:29])[CH3:28])[C:2](=[O:32])[NH:7][N:6]=1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 517045Sodium AcetateHCID 59834544(6-Chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile

Product 1

HCID 598345186-(2,6-Dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-oneYield 36%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (6-chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile (61) (332.8 mg, 0.61 mmol) and sodium acetate (103.8 mg, 1.26 mmol) in glacial acetic acid (2.7 mL) was heated to reflux for 2.5 h. The reaction was then treated with concentrated hydrochloric acid (2.0 mL) and heated to reflux for 18 h. At this time, the reaction was treated with more concentrated hydrochloric acid (6.0 mL) and additional glacial acetic acid (3.0 mL) and heated to reflux for an additional 24 h. The reaction was then cooled to 25° C. and diluted with ethyl acetate (150 mL). This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL) and a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. The resulting brown oil was treated with glacial acetic acid (1.0 mL) and concentrated hydrochloric acid (6.0 mL) and was heated to reflux for 3 d. At this time, the reaction was cooled to 25° C. and diluted with ethyl acetate (150 mL). This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL) and a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 2/1 hexanes/ethyl acetate) afforded 6-(2,6-dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one (62) (96.3 mg, 36%) as an off-white solid; LRMS for C15H15Br2ClN2O (M+H) at m/z=433. Molecular Weight=434.5606; Exact Mass=431.9240

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2.5 h
  3. temperatureheated
  4. temperatureto reflux for 18 h
  5. temperatureheated
  6. temperatureto reflux for an additional 24 h
  7. washThis solution was washed with a saturated aqueous sodium chloride solution (2×50 mL)
  8. dry with materiala saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. additionThe resulting brown oil was treated with glacial acetic acid (1.0 mL) and concentrated hydrochloric acid (6.0 mL)
  12. temperaturewas heated
  13. temperatureto reflux for 3 d
  14. temperatureAt this time, the reaction was cooled to 25° C.
  15. additiondiluted with ethyl acetate (150 mL)
  16. washThis solution was washed with a saturated aqueous sodium chloride solution (2×50 mL)
  17. dry with materiala saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate
  18. filtrationfiltered
  19. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-d7f57db02ed649599420c30750c10713
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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