Potassium Carbonate → 3-Chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine

HRID 1890938Notes

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.[K+].[K+]>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

Conditions

Temperature: 80 °C

Procedure

A mixture of 3,6-dichloropyridazine (20.1 g, 135 mmol), 1-methyl-4-pyrazoleboronic acid pinacol ester (22.46 g, 108 mmol) and K2CO3 (44.71 g, 324 mmol) in 500 mL of dioxane and 200 mL of H2O was degassed with nitrogen. To this mixture was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (5.28 g, 7.2 mmol) and the resulting mixture was bubbled with nitrogen for another 20 min. The reaction mixture was heated at 80° C. for 4 h, then concentrated in vacuo. The residue was purified by flash column chromatography with dichloromethane as eluent to provide 21 g of 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)-pyridazine (76% yield): 1H NMR (CDCl3) δ 3.99 (s, 3H), 7.45 (d, 1H), 7.56 (d, 1H), 7.97 (s, 1H), 8.11 (s, 1H).

Workup

customwas degassed with nitrogen
customthe resulting mixture was bubbled with nitrogen for another 20 min
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography with dichloromethane as eluent

Sources & evidence

ORD record: ord-e9a6de9adb664fb5a07fe8cd533b15ee
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507489B2

Reaction notes

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