Réaction #41652

Équation de réaction

tin(II) chloride dihydrate

sodium bicarbonate

2,5-difluoro-phenol

cesium carbonate

pyrazine-2-carboxylic acid (5-fluoro-4-(6-methanesulfonyl-pyridin-3-yloxy)-2-nitro-phenyl)-amide

→

compound

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

Solvants

ethyl acetate

N-methylpyrrolidinone

Conditions de réaction

Traitement

1. 1
   Autreobtained in (step 1)
2. 2
   Autrethe reaction liquid
3. 3
   AutreThe reaction liquid
4. 4
   workup.STIRRINGwas stirred at 90° C. for 1 hour
5. 5
   AutreThe deposit was removed through filtration
6. 6
   Autrethe solvent was evaporated away under reduced pressure
7. 7
   Autrethe residue was purified 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

15 mg of 2,5-difluoro-phenol and 28 mg of cesium carbonate were added to an N-methylpyrrolidinone (0.5 ml) solution of 26 mg of pyrazine-2-carboxylic acid (5-fluoro-4-(6-methanesulfonyl-pyridin-3-yloxy)-2-nitro-phenyl)-amide obtained in (step 1), and the reaction liquid was stirred at 90° C. for 15 minutes, and 100 mg of tin(II) chloride dihydrate was added to the reaction liquid. The reaction liquid was stirred at 90° C. for 1 hour, and ethyl acetate and aqueous saturated sodium bicarbonate were added to it. The deposit was removed through filtration, the solvent was evaporated away under reduced pressure, and the residue was 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 pale yellow solid.

Source