Lithium Chloride → 3-(2,4-Difluorophenyl)-5-[4-fluoro-3-(3-fluoropyridin-4-yl)phenyl]-[1,2,4]triazine

HRID 1064269

Reaktionsgleichung

Reaktionsgleichung von HRID 1064269
Br[C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[C:11]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[F:22])[N:12]=[N:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[F:8].[Cl-].[Li+].[F:25][C:26]1[CH:27]=[N:28][CH:29]=[CH:30][C:31]=1[Sn](CCCC)(CCCC)CCCC>O1CCOCC1>[F:22][C:16]1[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:15]=1[C:11]1[N:12]=[N:13][CH:14]=[C:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([C:31]3[CH:30]=[CH:29][N:28]=[CH:27][C:26]=3[F:25])[CH:3]=2)[N:10]=1

Komponenten

5

Edukt 3

HCID 433294Lithium ChlorideHCID 103842555-(3-Bromo-4-fluorophenyl)-3-(2,4-difluorophenyl)-[1,2,4]triazineHCID 222736013-Fluoro-4-(tributylstannyl)pyridine

Produkt 1

HCID 100684423-(2,4-Difluorophenyl)-5-[4-fluoro-3-(3-fluoropyridin-4-yl)phenyl]-[1,2,4]triazineAusbeute 42,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 5-(3-bromo-4-fluorophenyl)-3-(2,4-difluorophenyl)-[1,2,4]triazine (from Example 8 below) (120 mg, 0.33 mmol), lithium chloride (70 mg), cuprous iodide (6.3 mg) and 3-fluoro-4-tributylstannylpyridine (120 mg, 0.31 mmol) in dry 1,4-dioxane (5 ml) was degassed under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (30 mg) was added and the mixture heated under an atmosphere of nitrogen at 80° C. for 48 h. On cooling to room temperature the mixture was partitioned between dichloromethane (30 ml) and 25% aqueous ammonium hydroxide (15 ml). The organic layer was separated, solvent removed at reduced pressure, and the residue subjected to preparative thin layer chromatography on silica gel, eluent 2% methanol in dichloromethane. The product was recrystallised from hot toluene to give 3-(2,4-difluorophenyl)-5-[4-fluoro-3-(3-fluoropyridin-4-yl)phenyl]-[1,2,4]triazine as a solid (50 mg): δH (500 MHz, d6-DMSO) 7.35 (1H, m), 7.52 (1H, m), 7.73 (2H, m), 8.34 (1H, m), 8.63 (3H, m), 8.78 (1H, s), 10.18 (1H, s); m/z (ES+) 383.

Aufarbeitung

  1. customwas degassed under nitrogen
  2. additionTetrakis(triphenylphosphine)palladium(0) (30 mg) was added
  3. temperatureOn cooling to room temperature the mixture
  4. customwas partitioned between dichloromethane (30 ml) and 25% aqueous ammonium hydroxide (15 ml)
  5. customThe organic layer was separated
  6. customsolvent removed at reduced pressure
  7. customThe product was recrystallised from hot toluene

Quellen und Nachweise

ORD-Eintrag
ord-b6e4c8c44c2548d5ad61d67e054239ae
Quelldatensatz
uspto-grants-2005_11
Patentnummer
US06969716B2

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