6-Amino-3-chloropyridazine → 6-(2-Fluoro-4-(trifluoromethyl)phenyl)pyridazin-3-amine

HRID 1626440Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1626440
Cl[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1.[F:9][C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=1B(O)O.[F-].[Cs+].C(N(C(C)C)C(C)C)C>C(O)CC.CCOC(C)=O>[F:9][C:10]1[CH:15]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:13]=[CH:12][C:11]=1[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 216436-Amino-3-chloropyridazineHCID 25953Cesium fluorideHCID 81531DiisopropylethylamineHCID 164141452-Fluoro-4-(trifluoromethyl)benzeneboronic acid

Produkt 1

HCID 672882866-(2-Fluoro-4-(trifluoromethyl)phenyl)pyridazin-3-amineAusbeute 14,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 10311-PropanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 6-chloropyridazin-3-amine (0.300 g, 2.32 mmol), 2-fluoro-4-(trifluoromethyl)phenylboronic acid (0.626 g, 3.01 mmol), cesium fluoride (0.915 g, 6.02 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.449 g, 3.47 mmol) in propanol (17 ml) degassed with argon was added (dppf)palladium(II) chloride dichloromethane adduct (0.0953 g, 0.116 mmol), and the reaction was heated to 100° C. in a sealed tube for 3 hours. The reaction was cooled to ambient temperature, diluted with EtOAc, and washed with water and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel, eluting with a linear gradient of 0-10% methanol/EtOAc to yield the desired compound (0.086 g, 0.334 mmol, 14.4% yield).

Aufarbeitung

  1. temperatureThe reaction was cooled to ambient temperature
  2. washwashed with water and saturated sodium chloride
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash chromatography on silica gel
  7. washeluting with a linear gradient of 0-10% methanol/EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-d2902e3fe8f74865b1a3efa3b8db0376
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785445B2

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