Hydrochloric Acid → 4,5-difluoro-2-[[3-methyl-1-(3-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acid

HRID 498062

Reaktionsgleichung

Reaktionsgleichung von HRID 498062
Cl.Cl.[CH3:3][C:4]1[CH:8]=[C:7]([NH2:9])[N:6]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[N:5]=1.Cl[C:17]1[CH:25]=[C:24]([F:26])[C:23]([F:27])=[CH:22][C:18]=1[C:19]([OH:21])=[O:20].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.O>[F:26][C:24]1[C:23]([F:27])=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[C:17]([NH:9][C:7]2[N:6]([C:10]3[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=3)[N:5]=[C:4]([CH3:3])[CH:8]=2)[CH:25]=1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 7371712-Chloro-4,5-difluorobenzoic acidHCID 574176993-Methyl-1-(3-pyridinyl)-1H-pyrazol-5-ylamine dihydrochloride

Produkt 1

HCID 223203334,5-difluoro-2-[[3-methyl-1-(3-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acidAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 8895Cupric acetateKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 3-methyl-1-(3-pyridinyl)-1H-pyrazol-5-ylamine dihydrochloride (11.0 g, 44.5 mmol), 2-chloro-4,5-difluorobenzoic acid (8.57 g, 44.5 mmol), copper acetate (II) (0.808 g, 4.45 mmol) and potassium carbonate (12.3 g, 89.0 mmol) in N,N-dimethylformamide (50 mL) was heated under reflux under an argon atmosphere for 3 hours. The solution was allowed to cool to room temperature, and poured into water. The solution was made weakly acidic by the addition of 1N hydrochloric acid, and the resulting crude crystals were collected by filtration. The crystals were washed with water and air dried to give crude 4,5-difluoro-2-[[3-methyl-1-(3-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acid (9.24 g, 63% yield). A solution of the compound (9.24 g, 28.0 mmol) in phosphorous oxychloride (13 mL, 139 mmol) was heated under reflux for 3 hours. The solution was allowed to cool to room temperature, and the reaction solvent was concentrated and evaporated under reduced pressure. The residue was poured into iced water. The solution was neutralized by the addition of a sodium hydroxide solution, and the organic matter was extracted with chloroform. The extract was washed with saturated brine and water, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (chloroform) to give the title compound (0.77 g, 8% yield).

Aufarbeitung

  1. temperatureunder reflux under an argon atmosphere for 3 hours
  2. filtrationthe resulting crude crystals were collected by filtration
  3. washThe crystals were washed with water and air
  4. customdried

Quellen und Nachweise

ORD-Eintrag
ord-b958bf79c03446a3be2ea9e34ac908d9
Quelldatensatz
uspto-grants-2005_09
Patentnummer
US06949648B2

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