Reaktion #41573

Reaktionsgleichung

pyrazine-2-carboxylic acid

hydroxybenzotriazole

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydride

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

→

compound

5-(2-Cyano-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridin-3-yloxy)-1H-benzimidazole

Lösungsmittel

dimethylformamide

ethyl acetate

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe reaction liquid
2. 2
   SonstigeThe reaction liquid
3. 3
   Waschenwashed with aqueous saturated sodium bicarbonate, water and saturated saline in order
4. 4
   Trocknendried with anhydrous sodium sulfate
5. 5
   SonstigeThe solvent was evaporated away under reduced pressure
6. 6
   workup.DISSOLUTIONthe resulting residue was dissolved in 1 ml of N-methylpyrrolidinone
7. 7
   workup.ADDITION20 mg of ytterbium trifluoromethanesulfonate was added to it
8. 8
   Sonstigethe reaction liquid
9. 9
   workup.STIRRINGwas stirred at 160° C. for 2 h ours
10. 10
    SonstigeThe reaction liquid
11. 11
    Waschenwashed with aqueous saturated sodium bicarbonate and saturated saline in order
12. 12
    Trocknendried with anhydrous sodium sulfate
13. 13
    SonstigeThe solvent was evaporated away under reduced pressure
14. 14
    Sonstigethe resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=30/1)
15. 15
    Sonstigethrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1)

Vorschrift

21 mg of pyrazine-2-carboxylic acid, 52 mg of hydroxybenzotriazole and 52 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydride were added to a dimethylformamide (2 ml) solution of 72 mg of 4-(2-cyano-phenoxy)-5-(6-methanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamine obtained in Example 196 (step 5), and the reaction liquid was stirred at room temperature for 1 hour. The reaction liquid was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate, water and saturated saline in order, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was dissolved in 1 ml of N-methylpyrrolidinone, and 20 mg of ytterbium trifluoromethanesulfonate was added to it, and the reaction liquid was stirred at 160° C. for 2 h ours. The reaction liquid was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate and saturated saline in order, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=30/1) and through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1) to obtain the entitled compound as a brown solid.

Quelle