1-Methyl-3-aminopyrazole → 6-chloro-4-(1-methyl-1H-pyrazol-3-ylamino)pyridazin-3(2H)-one

HRID 872177Notes

Reaction equation

HRID 872177 reaction equation
Br[C:2]1[C:3](=[O:9])[NH:4][N:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:10][N:11]1[CH:15]=[CH:14][C:13]([NH2:16])=[N:12]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:8][C:6]1[CH:7]=[C:2]([NH:16][C:13]2[CH:14]=[CH:15][N:11]([CH3:10])[N:12]=2)[C:3](=[O:9])[NH:4][N:5]=1

Participants

7

Reactant 4

HCID 1372541-Methyl-3-aminopyrazoleHCID 115865224-Bromo-6-chloro-2,3-dihydropyridazin-3-oneHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxide

Product 1

HCID 666132646-chloro-4-(1-methyl-1H-pyrazol-3-ylamino)pyridazin-3(2H)-oneYield 25.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-bromo-6-chloropyridazin-3(2H)-one (838 mg, 4.0 mmol), 1-methyl-1H-pyrazol-3-amine (427 mg, 4.4 mmol), tris(dibenzylideneacetone)di-palladium(0) (91.6 mg, 0.1 mmol), and 2-di-tert-butylphosphino-2′,4′,6′-triisopropy-lbiphenyl, 97% (170 mg, 0.4 mmol) in 1,4-dioxane (12 mL) was added sodium tert-butoxide (845.7 mg, 8.8 mmol). The mixture was purged with nitrogen and sealed in a pressure tube. The reaction mixture was heated at 100° C. overnight. The mixture was cooled to room temperature, and filtered through Celite®. The filtrate was concentrated. The residue was purified on silica eluted with a gradient of 0 to 3.5% methanol in methylene chloride with 1% ammonium hydroxide to afford 6-chloro-4-(1-methyl-1H-pyrazol-3-ylamino)pyridazin-3(2H)-one (109g) (230 mg, 25%).

Workup

  1. customThe mixture was purged with nitrogen
  2. customsealed in a pressure tube
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered through Celite®
  5. concentrationThe filtrate was concentrated
  6. customThe residue was purified on silica
  7. washeluted with a gradient of 0 to 3.5% methanol in methylene chloride with 1% ammonium hydroxide

Sources & evidence

ORD record
ord-e72bf064171f487394fa3272cc44068d
Source dataset
uspto-grants-2015_03
Patent number
US08975260B2

Reaction notes

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