تفاعل #41652

معادلة التفاعل

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

المذيبات

ethyl acetate

N-methylpyrrolidinone

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر