反应详情

14.5 mg of pyrazine-2-carboxylic acid and 27.0 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydrochloride were added in order to a pyridine (1 ml) solution of 53 mg of 1-(2-(4,5-diamino-2-(4-methanesulfonyl-phenoxy)-phenyl)-pyrrolidin-1-yl)-2,2,2-trifluoro-ethanone obtained in Example 162 (step 6), and the reaction liquid was stirred at room temperature for 3 hours. The reaction liquid was diluted with saturated saline, and extracted with ethyl acetate. The organic layers were combined, washed with aqueous saturated ammonium chloride and aqueous saturated sodium bicarbonate in order, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was dissolved in 1 ml of toluene. 9.9 mg of p-toluenesulfonic acid monohydrate was added to it, and the reaction liquid was stirred at 120° C. for 6 hours. After cooled, the reaction liquid was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate and saturated saline in order, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and the residue was purified through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1) to obtain the entitled compound as an oily substance.

1. customthe reaction liquid
2. customThe reaction liquid
3. additionwas diluted with saturated saline
4. extractionextracted with ethyl acetate
5. washwashed with aqueous saturated ammonium chloride and aqueous saturated sodium bicarbonate in order
6. dry with materialdried with anhydrous magnesium sulfate
7. customThe solvent was evaporated away under reduced pressure
8. dissolutionthe resulting residue was dissolved in 1 ml of toluene
9. addition9.9 mg of p-toluenesulfonic acid monohydrate was added to it
10. customthe reaction liquid
11. stirringwas stirred at 120° C. for 6 hours
12. temperatureAfter cooled
13. customthe reaction liquid
14. washwashed with aqueous saturated sodium bicarbonate and saturated saline in order
15. dry with materialdried with anhydrous magnesium sulfate
16. customThe solvent was evaporated away under reduced pressure
17. customthe residue was purified
18. customthrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1)
19. customto obtain the entitled compound as an oily substance