Reaktion #324592

Reaktionsgleichung

8-(3-bromo-1H-indazol-5-yl)-6-methyl-1,3,4,8-tetrahydropyrido[2,1-c][1,4]oxazine-7,9-dicarbonitrile

8-(3-Bromo-1H-indazol-5-yl)-6-methyl-1,3,4,8-tetrahydropyrido[2,1-c][1,4]oxazine-7,9-dicarbonitrile

(6-fluoropyridin-3-yl)boronic acid

sodium bicarbonate

→

title compound

Ausbeute 49.3%

8-[3-(6-Fluoropyridin-3-yl)-1H-indazol-5-yl]-6-methyl-1,3,4,8-tetrahydropyrido[2,1-c][1,4]-oxazine-7,9-dicarbonitrile

Ausbeute 49.3%

Lösungsmittel

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   Einengenconcentration under reduced pressure
3. 3
   workup.DISSOLUTIONthe remaining solid was dissolved in ethyl acetate (20 ml)
4. 4
   WaschenThe solution was subsequently washed with water and with brine
5. 5
   Trocknendried over sodium sulfate
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   SonstigeThe crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 95:5 v/v)

Vorschrift

To a degassed solution of 125 mg (0.315 mmol) 8-(3-bromo-1H-indazol-5-yl)-6-methyl-1,3,4,8-tetrahydropyrido[2,1-c][1,4]oxazine-7,9-dicarbonitrile (Example 12A) and 53.3 mg (0.379 mmol) (6-fluoropyridin-3-yl)boronic acid in anhydrous 1,4-dioxane (2.2 ml) were added under inert gas atmosphere 36.5 mg (0.032 mmol) tetrakis(triphenylphosphine)palladium(0) and aqueous sodium bicarbonate solution (2 M, 0.56 ml). The resulting mixture was stirred at 140° C. for 70 min under microwave conditions. After cooling to room temperature and concentration under reduced pressure, the remaining solid was dissolved in ethyl acetate (20 ml). The solution was subsequently washed with water and with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 95:5 v/v) to yield the title compound as a white solid (64 mg, 49% of th.).

Quelle