Dimethylformamide → 1-(Imidazo[1,2-b]pyridazin-3-yl)ethan-1-one

HRID 2046418Notes

Reaction equation

HRID 2046418 reaction equation
Br[C:2]1[N:6]2[N:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:16]([O:18]CC)=[CH2:17])CCC.CN(C=O)C.O1CCOCC1>CO.Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:4]1[CH:3]=[C:2]([C:16](=[O:18])[CH3:17])[N:6]2[C:5]=1[CH:10]=[CH:9][CH:8]=[N:7]2

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 312751,4-DioxaneHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 128723193-Bromoimidazo(1,2-b)pyridazine

Product 1

HCID 450861961-(Imidazo[1,2-b]pyridazin-3-yl)ethan-1-one

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

3-Bromoimidazo[1,2-b]pyridazine (1.0 g, 5.05 mmol), tributyl(1-ethoxyvinyl)tin (3.41 mL, 10.1 mmol), and PdCl2(PPh3)2 (354 mg, 0.505 mmol), were added to a sealed tube. DMF (25.2 mL) was added and the reaction purged with nitrogen for 5 minutes. The reaction was heated at 100° C. for 18 h. The reaction was cooled to room temperature and quenched with aqueous saturated sodium bicarbonate. The aqueous layer was extracted with ethyl acetate (×3) and the combined organic layers were dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was diluted with methanol (10 mL) and HCl in 1,4-dioxane (1.26 mL, 5.05 mmol, 4M) was added. The solution was stirred at room temperature for 1 h. The reaction was then quenched with aqueous saturated sodium bicarbonate and extracted with ethyl acetate (×3). The combined organic layers were dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography to afford the title compound. 1H NMR (500 MHz, CD3SOCD3) δ 8.76 (d, 1H); 8.55 (s, 1H); 8.31 (d, 1H); 8.49 (dd, 1H); 2.64 (s, 3H). LRMS (APCI) calc'd for (C8H7N3O) [M+H]+, 162.1. found 162.1.

Workup

  1. customthe reaction purged with nitrogen for 5 minutes
  2. temperatureThe reaction was cooled to room temperature
  3. customquenched with aqueous saturated sodium bicarbonate
  4. extractionThe aqueous layer was extracted with ethyl acetate (×3)
  5. dry with materialthe combined organic layers were dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. additionwas added
  9. customThe reaction was then quenched with aqueous saturated sodium bicarbonate
  10. extractionextracted with ethyl acetate (×3)
  11. dry with materialThe combined organic layers were dried with magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-b75b64d5f82c49fb932b19e0617ac589
Source dataset
uspto-grants-2013_11
Patent number
US08592425B2

Reaction notes

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