Реакция #41576

Уравнение реакции

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

Растворители

dimethylformamide

ethyl acetate

chloroform

Условия реакции

Обработка

1. 1
   Другоеthe reaction liquid
2. 2
   ДругоеThe reaction liquid
3. 3
   Промывкаwashed with water
4. 4
   Сушкаdried with anhydrous sodium sulfate
5. 5
   ДругоеThe 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
   Другоеthe reaction liquid
8. 8
   workup.STIRRINGwas stirred at 120° C. for 2 hours
9. 9
   ДругоеThe reaction liquid
10. 10
    Промывкаwashed with water
11. 11
    Сушкаdried with anhydrous sodium sulfate
12. 12
    ДругоеThe solvent was evaporated away under reduced pressure
13. 13
    Другоеthe resulting residue was purified
14. 14
    Другоеthrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)

Методика

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.

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