Reacción #41576

Ecuación de reacción

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

Disolventes

dimethylformamide

ethyl acetate

chloroform

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente