Ethyl Acetate → 6-Bromo-4-(pyridazin-4-yl)quinoline

HRID 472090Notes

Reaction equation

HRID 472090 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2I.C([Sn](CCCC)(CCCC)[C:18]1[CH:23]=[CH:22][N:21]=[N:20][CH:19]=1)CCC.CCOC(C)=O>O1CCOCC1.[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[C:18]1[CH:23]=[CH:22][N:21]=[N:20][CH:19]=1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 64097334-(Tributylstannyl)pyridazineHCID 177505956-Bromo-4-iodoquinoline

Product 1

HCID 667823086-Bromo-4-(pyridazin-4-yl)quinolineYield 38.8%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

Dissolved 6-bromo-4-iodoquinoline (17.43 g, 52.2 mmol), 4-(tributylstannanyl)pyridazine (19.27 g, 52.2 mmol), and PdCl2(dppf)-CH2Cl2 (2.132 g, 2.61 mmol) in 1,4-dioxane (200 mL) and heated to 105° C. After 3 h, added more palladium catalyst and heated for 6 h. Concentrated and dissolved in methylene chloride/methanol. Purified by column chromatography (combiflash) with 2% MeOH/EtOAc to 5% MeOH/EtOAc to give the crude title compound. Trituration with EtOAc furnished 6-bromo-4-(4-pyridazinyl)quinoline (5.8 g, 20.27 mmol, 38.8% yield). MS (ES)+ m/e 285.9, 287.9 [M+H]+.

Workup

  1. temperatureheated for 6 h
  2. concentrationConcentrated
  3. dissolutiondissolved in methylene chloride/methanol
  4. customPurified by column chromatography (combiflash) with 2% MeOH/EtOAc to 5% MeOH/EtOAc
  5. customto give the crude title compound

Sources & evidence

ORD record
ord-cd015fb0385d46b0b64f7e1c833e69b9
Source dataset
uspto-grants-2014_01
Patent number
US08633187B2

Reaction notes

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