반응 #324592

반응 방정식

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

수율 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

수율 49.3%

용매

1,4-dioxane

반응 조건

후처리

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

실험 절차

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.).

출처