Reacción #41652

Ecuación de reacción

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

Disolventes

ethyl acetate

N-methylpyrrolidinone

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroobtained in (step 1)
2. 2
   Otrothe reaction liquid
3. 3
   OtroThe reaction liquid
4. 4
   workup.STIRRINGwas stirred at 90° C. for 1 hour
5. 5
   OtroThe deposit was removed through filtration
6. 6
   Otrothe solvent was evaporated away under reduced pressure
7. 7
   Otrothe 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
   Lavadowashed with aqueous saturated sodium bicarbonate
10. 10
    Secadodried with anhydrous sodium sulfate
11. 11
    OtroThe solvent was evaporated away under reduced pressure

Procedimiento

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.

Fuente