Reacción #41611

Ecuación de reacción

tin(II) chloride dihydrate

p-toluenesulfonic acid

2,6-difluorophenol

potassium carbonate

N-(2,3-difluoro-4-(6-methanesulfonyl-pyridin-3-yloxy)-6-nitro-phenyl)pyrazinecarboxamide

→

compound

5-(2,6-difluoro-phenoxy)-4-fluoro-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridin-3-yloxy)-1H-benzimidazole

Disolventes

N-methylpyrrolidinone

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe reaction liquid
2. 2
   Otrothe reaction liquid
3. 3
   workup.STIRRINGwas stirred overnight at 90° C
4. 4
   Otrothe reaction liquid
5. 5
   workup.STIRRINGwas stirred at 90° C. for 2 hours
6. 6
   FiltraciónThe deposit was taken out through filtration
7. 7
   Otropurified through reversed-phase middle-pressure liquid chromatography [ODS-AS-360-CC (by YMC), mobile phase: water-acetonitrile-0.1% trifluoroacetic acid]
8. 8
   workup.ADDITIONThe solvent of the resulting fraction was diluted with ethyl acetate
9. 9
   Lavadowashed with aqueous saturated sodium bicarbonate
10. 10
    Secadodried with anhydrous sodium sulfate
11. 11
    OtroThe solvent was evaporated away under reduced pressure

Procedimiento

8 mg of 2,6-difluorophenol and 8 mg of potassium carbonate were added to an N-methylpyrrolidinone (0.5 ml) solution of 8.6 mg of N-(2,3-difluoro-4-(6-methanesulfonyl-pyridin-3-yloxy)-6-nitro-phenyl)pyrazinecarboxamide, and the reaction liquid was stirred at 90° C. for 15 minutes. 75 mg of tin(II) chloride dihydrate was added to it, and the reaction liquid was stirred overnight at 90° C. Further, 3 mg of p-toluenesulfonic acid was added to it, and the reaction liquid was stirred at 90° C. for 2 hours. The deposit was taken out through filtration, and purified through reversed-phase middle-pressure liquid chromatography [ODS-AS-360-CC (by YMC), mobile phase: water-acetonitrile-0.1% trifluoroacetic acid]. The solvent of the resulting fraction was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure to obtain the entitled compound as a brown solid.

Fuente