Potassium Fluoride → 6'-Chloro-2,5'-difluoro(3,4'-bipyridin)-3'-amine

HRID 60237

Reaktionsgleichung

Reaktionsgleichung von HRID 60237
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4](I)[C:3]=1[F:10].[F:11][C:12]1[C:17](B(O)O)=[CH:16][CH:15]=[CH:14][N:13]=1.[F-].[K+]>C(#N)C.O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:17]2[C:12]([F:11])=[N:13][CH:14]=[CH:15][CH:16]=2)[C:3]=1[F:10]

Komponenten

6

Edukt 3

HCID 522689Potassium FluorideHCID 27832702-Fluoropyridine-3-boronic acidHCID 583650336-Chloro-5-fluoro-4-iodopyridin-3-amine

Produkt 1

HCID 583650006'-Chloro-2,5'-difluoro(3,4'-bipyridin)-3'-amineAusbeute 75,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A degassed mixture of 6-chloro-5-fluoro-4-iodopyridin-3-ylamine (98.7 g, 362 mmol), 2-fluoropyridine 3-boronic acid (68.3 g, 485 mmol), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (7.7 g, 10.9 mmol) and potassium fluoride (63 g, 1.09 mol) in a mixture of acetonitrile (900 mL) and water (275 mL) was heated at 90° C. for 2 hours. The reaction mixture was allowed to cool to ambient temperature and filtered through Celite© and washed through with ethyl acetate. The filtrate was diluted with ethyl acetate and the organic layer collected, dried (Na2SO4), filtered and concentrated in-vacuo to afford a residue. The resultant residue was triturated with diethyl ether to afford the title compound as a grey solid (65.8 g, 75%). The trituration liquors were concentrated and purified by flash chromatography (silica: dichloromethane to 20% ethyl acetate/dichloromethane) to afford, after trituration with ether, an additional batch of the title compound as a grey solid (9.7 g, 11%). Total yield=75.5 g, 86%. 1H NMR (400 MHz, CDCl3): 8.39 (ddd, J=4.9, 2.0, 1.1 Hz, 1H), 7.86-7.84 (m, 2H), 7.39 (ddd, J=7.4, 4.9, 1.9 Hz, 1H).

Aufarbeitung

  1. temperatureto cool to ambient temperature
  2. filtrationfiltered through Celite©
  3. washwashed through with ethyl acetate
  4. additionThe filtrate was diluted with ethyl acetate
  5. customthe organic layer collected
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in-vacuo
  9. customto afford a residue
  10. customThe resultant residue was triturated with diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-cf0f2ad0946a48268431403b500b8bb8
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440976B2

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