Réaction #41611

Équation de réaction

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

Solvants

N-methylpyrrolidinone

Conditions de réaction

Traitement

1. 1
   Autrethe reaction liquid
2. 2
   Autrethe reaction liquid
3. 3
   workup.STIRRINGwas stirred overnight at 90° C
4. 4
   Autrethe reaction liquid
5. 5
   workup.STIRRINGwas stirred at 90° C. for 2 hours
6. 6
   FiltrationThe deposit was taken out through filtration
7. 7
   Autrepurified 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
   Lavagewashed with aqueous saturated sodium bicarbonate
10. 10
    Séchagedried with anhydrous sodium sulfate
11. 11
    AutreThe solvent was evaporated away under reduced pressure

Mode opératoire

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.

Source