Potassium Carbonate → 3-Amino-6-(4-fluorophenyl)picolinamide

HRID 1517446Notes

Reaction equation

HRID 1517446 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([NH2:11])=[O:10])=[N:4][C:5](Cl)=[CH:6][CH:7]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2]1[C:3]([C:9]([NH2:11])=[O:10])=[N:4][C:5]([C:16]2[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 107497043-Amino-6-chloropyridine-2-carboxamide

Product 1

HCID 596479063-Amino-6-(4-fluorophenyl)picolinamideYield 85%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-amino-6-chloropyridine-2-carboxylic acid amide (2.57 g, 15 mmol) in dioxane (200 ml) and water (50 ml) was added 4-fluorophenylboronic acid (2.1 g, 15 mmol), K2CO3 (6.2 g, 45 mmol), and tetrakis(triphenylphosphine) palladium(0) (860 mg, 0.75 mmol). The mixture was heated at reflux for 3 hours. After cooling to room temperature, the reaction mixture was concentrated to a small volume, filtrated and washed with water to yield a crude product. The residue was purified by silica gel flash chromatography, the mobile phase being a mixture of methanol and dichloromethane, in a volume ratio of 1:80, yielding the title compound (2.9 g, yield 85%) as a white solid. The mass spectrum characterising data was as follows: MS (m/z): 232 ([M+H]+, 100).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3 hours
  3. concentrationthe reaction mixture was concentrated to a small volume
  4. filtrationfiltrated
  5. washwashed with water
  6. customto yield a crude product
  7. customThe residue was purified by silica gel flash chromatography
  8. additiona mixture of methanol and dichloromethane

Sources & evidence

ORD record
ord-76546f6eda764381aad07a2b3d4d8508
Source dataset
uspto-grants-2012_07
Patent number
US08232278B2

Reaction notes

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