Reaction #41576

Reaction equation

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

Solvents

dimethylformamide

ethyl acetate

chloroform

Conditions

Workup

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

Procedure

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.

Source