Réaction #41573

Équation de réaction

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

Solvants

dimethylformamide

ethyl acetate

ethyl acetate

Conditions de réaction

Traitement

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

Mode opératoire

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.

Source