反应详情

A mixture of 3-(butylamino)-5-(pyridin-4-yl)thiophene-2-carboxylic acid (0.370 g, 1.34 mmol), ammonium chloride (0.717 g, 13.4 mmol), triethylamine (1.88 mL, 13.4 mmol) and DMF (8.0 mL) was stirred for 5 min. Then, 1-hydroxybenzotriazole (0.541 g, 4.00 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.767 g, 4.00 mmol) were added and stirring was continued for 3 days. The mixture was then poured into sat. aqueous sodium hydrogen carbonate (100 mL) and water (60 mL). Extraction with ethyl acetate-tetrahydrofuran (3:1, 2×100 mL), washing with sat. aqueous sodium hydrogen carbonate and brine, drying over magnesium sulfate, filtration and concentration at reduced pressure gave a yellow solid. This solid was triturated with dichloromethane, and the precipitate was collected by filtration to afford the title compound (0.202 g, 55%) as a yellow solid. The filtrate was purified by column chromatography (Combiflash, 12 g silica gel, dichloromethane to ethyl acetate) to afford the additional title compound (0.067 g, 18%):

1. stirringstirring
2. waitwas continued for 3 days
3. extractionExtraction with ethyl acetate-tetrahydrofuran (3:1, 2×100 mL)
4. washwashing with sat. aqueous sodium hydrogen carbonate and brine
5. dry with materialdrying over magnesium sulfate, filtration and concentration at reduced pressure
6. customgave a yellow solid
7. customThis solid was triturated with dichloromethane
8. filtrationthe precipitate was collected by filtration