반응 #41652

반응 방정식

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

용매

ethyl acetate

N-methylpyrrolidinone

반응 조건

후처리

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

실험 절차

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.

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