反应详情

温度

27.5 °C

To a stirred solution of 4,6-dichloro-5-(2-methoxyphenoxy)-2,2′-bipyrimidine (50 gm) in acetonitrile (500 ml), potassium carbonate (150 gm) and 4-tert-butylbenzenesulfonamide (33.58 gm) were added and the reaction mass was heated to 80° C. to 85° C. for 5 to 6 hours. After completion of the reaction, ethylene glycol (262.5 gm) was added to the reaction mass at 85° C. to 90° C. and the reaction mass was maintained at same temperature for 16 to 18 hours till the reaction completion. The reaction mass was then cooled to 25 to 30° C. and water (500 ml) was added to it. The pH of the reaction mass was adjusted to 2 to 3 using concentrated hydrochloric acid. Dichloromethane (500 ml) was added to the reaction mass and the mixture was stirred for 30 minutes. The dichloromethane layer was separated and it was washed with water (500 ml). The layer was concentrated under reduced pressure to obtain the syrup. Methanol (160 ml) and water (80 ml) were added to the syrup and the mixture was heated to 55° C. to 60° C. for 30 minutes under stirring. The reaction mixture was then cooled to 25° C. to 30° C. for 40 to 45 minutes and the solid obtained was filtered. The solid was washed with methanol (40 ml) to obtain the crude Bosentan (wet weight around 75 gm). To the crude Bosentan (75 gm), isopropyl acetate (225 ml), ethanol (75 ml), and ammonium hydroxide solution (37.2 ml) were added and the mixture was heated to 55° C. to 60° C. for 30 minutes. The reaction mass was then cooled to 0° C. to 5° C. and maintained at 0° C. to 5° C. for 3 to 4 hours. The precipitated pure Bosentan ammonium salt was filtered (yield, 60 gm), washed with chilled isopropylacetate and dried.

1. temperaturethe reaction mass was heated to 80° C. to 85° C. for 5 to 6 hours
2. additionwas added to the reaction mass at 85° C. to 90° C.
3. temperaturethe reaction mass was maintained at same temperature for 16 to 18 hours till the reaction completion
4. customThe dichloromethane layer was separated
5. washit was washed with water (500 ml)
6. concentrationThe layer was concentrated under reduced pressure
7. customto obtain the syrup
8. temperaturethe mixture was heated to 55° C. to 60° C. for 30 minutes
9. stirringunder stirring
10. temperatureThe reaction mixture was then cooled to 25° C. to 30° C. for 40 to 45 minutes
11. customthe solid obtained
12. filtrationwas filtered
13. washThe solid was washed with methanol (40 ml)