反应详情

Tert-butyl 4-[2-(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazol-2,4′-piperidin]-1′-yl)-2-oxoethyl]piperazine-1-carboxylate prepared in Example 653 (300 mg, 0.67 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (10 ml) was added followed by stirring at room temperature for 6 hours. The reaction mixture was concentrated under reduced pressure. To the residue, methylene chloride (1 ml) and triethylamine (1 ml) were added followed by stirring at room temperature for 5 minutes, and then the solution was concentrated under reduced pressure. The residue was dissolved in DMF (10 ml). To the solution, 2-bromo-N-(4-trifluoromethylphenyl)acetamide (207 mg, 0.73 mmol) and triethylamine (0.28 ml, 2.0 mmol) were added followed by stirring at 100° C. for 2 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with a saturated saline solution, dried over magnesium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1) and crystallized from methylene chloride-diisopropyl ether to afford 2-{4-[2-(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazole-2,4′-piperidin]-1′-yl)-2-oxoethyl]piperazin-1-yl}-N-[4-trifluoromethylphenyl]acetamide (275 mg, yield 75%) as a white powder.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionTo the residue, methylene chloride (1 ml) and triethylamine (1 ml) were added
3. stirringby stirring at room temperature for 5 minutes
4. concentrationthe solution was concentrated under reduced pressure
5. dissolutionThe residue was dissolved in DMF (10 ml)
6. stirringby stirring at 100° C. for 2 hours
7. extractionextracted with ethyl acetate
8. washThe organic phase was washed with a saturated saline solution
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationThe resulting filtrate was concentrated under reduced pressure
12. customthe residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1)
13. customcrystallized from methylene chloride-diisopropyl ether