تفاعل #41576

معادلة التفاعل

1-methyl-1H-pyrazole-3-carboxylic acid

hydroxybenzotriazole

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydrochloride

4-(2-fluoro-phenoxy)-5-(6-methanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamine

→

compound

5-(2-Fluoro-phenoxy)-2-(1-methyl-1H-pyrazol-3-yl)-6-(6-methanesulfonyl-pyridin-3-yloxy)-1H-benzimidazole

المذيبات

dimethylformamide

ethyl acetate

chloroform

ظروف التفاعل

المعالجة

1. 1
   أخرىthe reaction liquid
2. 2
   أخرىThe reaction liquid
3. 3
   غسيلwashed with water
4. 4
   تجفيفdried with anhydrous sodium sulfate
5. 5
   أخرىThe solvent was evaporated away under reduced pressure, and 3 mg of p-toluenesulfonic acid
6. 6
   workup.ADDITIONwas added to the resulting residue
7. 7
   أخرىthe reaction liquid
8. 8
   workup.STIRRINGwas stirred at 120° C. for 2 hours
9. 9
   أخرىThe reaction liquid
10. 10
    غسيلwashed with water
11. 11
    تجفيفdried with anhydrous sodium sulfate
12. 12
    أخرىThe solvent was evaporated away under reduced pressure
13. 13
    أخرىthe resulting residue was purified
14. 14
    أخرىthrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)

الإجراء التجريبي

4.3 mg of 1-methyl-1H-pyrazole-3-carboxylic acid, 6.0 mg of hydroxybenzotriazole and 8.5 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydrochloride were added to a dimethylformamide (0.5 ml) solution of 15 mg of 4-(2-fluoro-phenoxy)-5-(6-methanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamine obtained in Example 200, and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with chloroform, washed with water, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 3 mg of p-toluenesulfonic acid was added to the resulting residue, and the reaction liquid was stirred at 120° C. for 2 hours. The reaction liquid was diluted with ethyl acetate, washed with water, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1) to obtain the entitled compound as a white solid.

المصدر