反应详情

温度

60 °C

To a suspension of 300 mg of 8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid in 5 ml of THF was added 253 mg of 1,1′-carbonyldiimidazole, followed by stirring at 60° C. for 1 hour. Subsequently, 283 mg of 3-(aminosulfonyl)propyl acetate and 389 μl of 1,8-diazabicyclo[5.4.0]-7-undecene were added thereto under ice-cooling, followed by stirring at room temperature overnight. To the reaction mixture were added water and ethyl acetate to carry out a layer separation operation. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography. Since the reaction was not completed, to the obtained purified product were added again 57 mg of 3-(aminosulfonyl)propyl acetate, 60 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride, 38 mg of 4-(dimethylamino)pyridine, and 2 ml of DMF, followed by stirring at room temperature overnight. To the reaction mixture were added a saturated aqueous ammonium chloride solution and chloroform to carry out a layer separation operation. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography. To the obtained product were added ethyl acetate and ethanol, followed by stirring. The resulting solid was collected by filtration and dried to obtain 149 mg of 3-[({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)sulfonyl]propyl acetate.

1. temperatureunder ice-cooling
2. stirringby stirring at room temperature overnight
3. customa layer separation operation
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over anhydrous sodium sulfate
6. customthe solvent was evaporated under reduced pressure
7. customthe obtained residue was purified by silica gel column chromatography
8. custompurified product
9. additionwere added again 57 mg of 3-(aminosulfonyl)propyl acetate, 60 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride, 38 mg of 4-(dimethylamino)pyridine, and 2 ml of DMF
10. stirringby stirring at room temperature overnight
11. additionTo the reaction mixture were added a saturated aqueous ammonium chloride solution and chloroform
12. customa layer separation operation
13. dry with materialThe organic layer was dried over anhydrous sodium sulfate
14. customthe solvent was evaporated under reduced pressure
15. customthe obtained residue was purified by silica gel column chromatography
16. additionTo the obtained product were added ethyl acetate and ethanol
17. stirringby stirring
18. filtrationThe resulting solid was collected by filtration
19. customdried