反应详情

A mixture of 2-(4-tert-butoxycarbonylpiperazin-1-yl)methyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole prepared in Example 306 (500 mg, 1.36 mmol) and trifluoroacetic acid (15 ml) was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in methylene chloride (10 ml) and added triethylamine (2 ml, 14.35 mmol). The solution was concentrated under reduced pressure, and the residue was dissolved in DMF (10 ml). To the solution, 2-bromo-N-(4-trifluoromethylphenyl)acetamide (423 mg, 1.5 mmol), potassium carbonate (207 mg, 1.5 mmol), and sodium iodide (204 mg, 1.36 mmol) were added followed by stirring at room temperature for 5 hours. To the reaction mixture, water was added, and the solution was extracted with ethyl acetate twice. The organic phases were combined, washed with water three times and a saturated saline solution, dried over sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1) to afford 2-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]-N-(4-trifluoromethylphenyl)acetamide (389 mg, yield 61%) as a white powder.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionThe residue was dissolved in methylene chloride (10 ml)
3. concentrationThe solution was concentrated under reduced pressure
4. dissolutionthe residue was dissolved in DMF (10 ml)
5. stirringby stirring at room temperature for 5 hours
6. extractionthe solution was extracted with ethyl acetate twice
7. washwashed with water three times
8. dry with materiala saturated saline solution, dried over sodium sulfate
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure
11. customthe residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1)