Potassium Carbonate → 3-Chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine
Reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4](B2OC(C)(C)C(C)(C)O2)=[N:3]1.[Cl:16][C:17]1[N:18]=[N:19][C:20](Cl)=[CH:21][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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]>[Cl:16][C:17]1[N:18]=[N:19][C:20]([C:5]2[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=2)=[CH:21][CH:22]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 80 °C
Procedure
To a 3000 mL round bottom flask containing a solution of 1-methyl-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (76 g, 365.3 mmol), 3,6-dichloropyridazine (68 g, 456.4 mmol) in 1,4-dioxane (1200 mL) is added a aqueous solution of K2CO3 (127 g, 919 mmol) in water (480 mL). After [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (7.5 g, 9.2 mmol) is added, the mixture is purged with N2 for 20 min and stirred at 80° C. for 16 h. The reaction mixture is poured into water (300 mL) and dichloromethane (2000 mL), and the aqueous layer is extracted with DCM (3×800 mL). The combined organic layers are dried over anhydrous Na2SO4 and concentrated under vacuum. The crude product is purified with silica gel column eluting with DCM/methanol (40:1) to give the title compound as a pale yellow solid (56 g, 63.1%). MS (m/z): 195.1 (M+H).
Workup
- customthe mixture is purged with N2 for 20 min
- additionThe reaction mixture is poured into water (300 mL) and dichloromethane (2000 mL)
- extractionthe aqueous layer is extracted with DCM (3×800 mL)
- dry with materialThe combined organic layers are dried over anhydrous Na2SO4
- concentrationconcentrated under vacuum
- customThe crude product is purified with silica gel column
- washeluting with DCM/methanol (40:1)
Sources & evidence
- ORD record
- ord-b225c37ff1964f399bb47635bfa6c83b
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08268836B2
Reaction notes
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