Cesium carbonate → 3-Chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine

HRID 655228Notes

Reaction equation

HRID 655228 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][CH:7]=1.[CH3:9][N:10]1[CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[CH:12]=[N:11]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Cl:1][C:2]1[N:3]=[N:4][C:5]([C:13]2[CH:12]=[N:11][N:10]([CH3:9])[CH:14]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 673313,6-DichloropyridazineHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 545956073-Chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazineYield 60%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3,6-dichloropyridazine (5.37 g, 33.5 mmol), 1-methyl-4-pyrazoleboronic acid pinacol ester (5 g, 24.0 mmol) and cesium carbonate (23.44 g, 72 mmol) in 1,4-dioxane (150 mL) and water (750 mL) under nitrogen was degassed by bubbling in nitrogen for 15 min. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (1 g, 1.37 mmol) was than added and nitrogen was bubbled in the mixture for another 10 min. The reaction mixture was stirred at 80° C. for 2.5 h, then cooled to room temperature and concentrated in vacuo. The residue was partitioned between 1 N aqueous potassium carbonate and ethyl acetate. The organic layer was washed with 1 N aqueous potassium carbonate and brine, dried over sodium sulfate, filtered and adsorbed on silica gel for purification. Purification by flash chromatography on silica gel using a gradient of 0-50% ethyl acetate/hexane afforded 2.8 g of the title compound as a white solid (60% yield); MS (m/z) 195 [M+H+]+.

Workup

  1. customwas degassed
  2. customby bubbling in nitrogen for 15 min
  3. additionthan added
  4. customnitrogen was bubbled in the mixture for another 10 min
  5. temperaturecooled to room temperature
  6. concentrationconcentrated in vacuo
  7. customThe residue was partitioned between 1 N aqueous potassium carbonate and ethyl acetate
  8. washThe organic layer was washed with 1 N aqueous potassium carbonate and brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customadsorbed on silica gel for purification
  12. customPurification by flash chromatography on silica gel using a gradient of 0-50% ethyl acetate/hexane

Sources & evidence

ORD record
ord-a34dc38d0f6d45db924edb816da1d0f6
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

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