反应详情

To a solution of rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid (55 mg) in N,N-dimethylformamide (5 mL) were added 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (70 mg) and 1-hydroxybenzotriazole (49 mg), followed by stirring at room temperature for 30 minutes. To the reaction mixture was added thiomorpholine 1,1-dioxide (49 mg), followed by stirring at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, and to the obtained residue was added water, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: chloroform-methanol=100:0 to 95:5). To the obtained residue was added ethanol (3 mL), followed by heating and dissolving, and then stirring at room temperature for 1 hour. The precipitated colorless solid was collected by filtration, washed with a small amount of ethanol, and then dried to obtain rac-4-({2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidin-5-yl}carbonyl)thiomorpholine 1,1-dioxide (45 mg).

1. stirringby stirring at room temperature for 15 hours
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. additionto the obtained residue was added water
4. extractionfollowed by extraction with ethyl acetate
5. washThe obtained organic layer was washed with saturated brine
6. dry with materialdried over anhydrous magnesium sulfate
7. customthe solvent was evaporated under reduced pressure
8. customThe obtained residue was purified by silica gel column chromatography (eluent: chloroform-methanol=100:0 to 95:5)
9. additionTo the obtained residue was added ethanol (3 mL)
10. temperatureby heating
11. dissolutiondissolving
12. stirringstirring at room temperature for 1 hour
13. filtrationThe precipitated colorless solid was collected by filtration
14. washwashed with a small amount of ethanol
15. customdried