Potassium Carbonate → 1-(cyclopropylmethyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1747813Notes

Reaction equation

HRID 1747813 reaction equation
Cl[C:2]1[C:7](=[O:8])[C:6]([O:9][CH3:10])=[CH:5][N:4]([CH2:11][CH:12]2[CH2:14][CH2:13]2)[N:3]=1.[C:15]1([N:21]2[C:25](B3OC(C)(C)C(C)(C)O3)=[CH:24][CH:23]=[N:22]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.C(=O)([O-])O.[Na+].[Cl-].[Na+].O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH:12]1([CH2:11][N:4]2[CH:5]=[C:6]([O:9][CH3:10])[C:7](=[O:8])[C:2]([C:25]3[N:21]([C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)[N:22]=[CH:23][CH:24]=3)=[N:3]2)[CH2:14][CH2:13]1

Participants

9

Reactant 3

HCID 11430Potassium CarbonateHCID 580723671-Phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 895861593-chloro-1-(cyclopropylmethyl)-5-methoxypyridazin-4(1H)-one

Product 1

HCID 680148501-(cyclopropylmethyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 59.6%

Reagents, catalysts & solvents 5

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 516892Sodium BicarbonateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

3-Chloro-1-(cyclopropylmethyl)-5-methoxypyridazin-4(1H)-one (0.133 g), 1-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.200 g), potassium carbonate (0.171 g) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.0219 g) were suspended in toluene (3.09 mL) and water (0.309 mL), and the suspension was heated under reflux for 20 hr under an argon atmosphere. The reaction mixture was cooled to room temperature, diluted with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated, purified by NH silica gel column chromatography (ethyl acetate/hexane→methanol/ethyl acetate) and recrystallized from ethyl acetate/hexane to give the title compound (0.119 g).

Workup

  1. temperatureunder reflux for 20 hr under an argon atmosphere
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by NH silica gel column chromatography (ethyl acetate/hexane→methanol/ethyl acetate)
  7. customrecrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-eb3e4e029e5b4b15b88a55422355d6cf
Source dataset
uspto-grants-2015_10
Patent number
US09150588B2

Reaction notes

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