반응 #41573

반응 방정식

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

용매

dimethylformamide

ethyl acetate

ethyl acetate

반응 조건

후처리

1. 1
   기타the reaction liquid
2. 2
   기타The reaction liquid
3. 3
   세척washed with aqueous saturated sodium bicarbonate, water and saturated saline in order
4. 4
   건조dried with anhydrous sodium sulfate
5. 5
   기타The 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
   기타the reaction liquid
9. 9
   workup.STIRRINGwas stirred at 160° C. for 2 h ours
10. 10
    기타The reaction liquid
11. 11
    세척washed with aqueous saturated sodium bicarbonate and saturated saline in order
12. 12
    건조dried with anhydrous sodium sulfate
13. 13
    기타The solvent was evaporated away under reduced pressure
14. 14
    기타the resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=30/1)
15. 15
    기타through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1)

실험 절차

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.

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