Potassium Carbonate → Methyl 1-(5-fluoropyridin-2-yl)-3-phenyl-1H-pyrazole-4-carboxylate

HRID 1842564Notes

Reaction equation

HRID 1842564 reaction equation
[C:1]1([C:7]2[C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1.CN[C@H]1CCCC[C@@H]1NC.C(=O)([O-])[O-].[K+].[K+].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.[Cu]I>[F:23][C:20]1[CH:21]=[CH:22][C:17]([N:9]2[CH:10]=[C:11]([C:12]([O:14][CH3:15])=[O:13])[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:8]2)=[N:18][CH:19]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 27831712-Bromo-5-fluoropyridineHCID 13822957(1S,2S)-(+)-N,N'-Dimethylcyclohexane-1,2-diamine2×HCID 178498885HCID 178498885, compound

Product 1

HCID 66679523Methyl 1-(5-fluoropyridin-2-yl)-3-phenyl-1H-pyrazole-4-carboxylateYield 74.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of methyl 3-phenyl-1H-pyrazole-4-carboxylate (0.50 g, 2.47 mmol) in toluene (9.9 mL) were added 2-bromo-5-fluoropyridine (0.52 g, 2.97 mmol), (1S,2S)—N,N′-dimethylcyclohexane-1,2-diamine (78 μL, 0.50 mmol), copper(I) iodide (24.0 mg, 0.12 mmol) and potassium carbonate (0.72 g, 5.19 mmol). The mixture was heated in a microwave reactor for 20 min at 150° C. Additional (1S,2S)—N,N′-dimethylcyclohexane-1,2-diamine (78 μL, 0.50 mmol) and copper(I) iodide (24.0 mg, 0.12 mmol) were added and the mixture was heated in the microwave reactor for another 20 min at 160° C. Saturated aqueous NaHCO3 was added and the mixture was extracted with dichloromethane (3×). The combined organic extracts was dried over MgSO4, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol) gave the title compound (0.55 g). MS 298.1 (M+1).

Workup

  1. temperaturethe mixture was heated in the microwave reactor for another 20 min at 160° C
  2. extractionthe mixture was extracted with dichloromethane (3×)
  3. dry with materialThe combined organic extracts was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol)

Sources & evidence

ORD record
ord-0ed58b93d71e44af943f7bd6178717a5
Source dataset
uspto-grants-2015_02
Patent number
US08946231B2

Reaction notes

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