反应详情

To 3-(2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-propanol (12.2 g, 50.56 mmol) dissolved in dichloromethane (180 mL) was added sodium hydroxide (180 mL of 50%) with mechanical stirring. Benzyltrimethylammonium chloride (1.88 g, 10.11 mmol) was added to the resulting suspension, and after stirring for 5 minutes, propargyl bromide (17 mL of 80% in toluene, 141.8 mmol) was added. The resulting reaction mixture was allowed to stir at ambient temperature. After 2 hours, TLC monitoring indicated 50% completion, and after 4.5 hours HPLC monitoring indicated 20% starting material remaining. More propargyl bromide (5 mL of 80% in toluene, 40.51 mmol) was added, and the resulting reaction mixture was allowed to stir at ambient temperature for 64.5 hours. The layers were separated, and the organic layer was washed with water (3×) and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting dark oil was dissolved in dichloromethane and again extracted with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting dark oil was purified by silica gel column chromatography using 98/2 dichloromethane/methanol as the eluant. After removing the solvent from the collected fractions, 5.880 g of pure (by HNMR analysis) product was obtained. This material was recrystallized from ethyl acetate/hexane to provide 4.658 g of brown crystals.

1. customThe resulting reaction mixture
2. stirringto stir at ambient temperature
3. waitAfter 2 hours
4. waitafter 4.5 hours HPLC monitoring indicated
5. customthe resulting reaction mixture
6. stirringto stir at ambient temperature for 64.5 hours
7. customThe layers were separated
8. washthe organic layer was washed with water (3×) and brine
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. dissolutionThe resulting dark oil was dissolved in dichloromethane
13. extractionagain extracted with water
14. dry with materialdried over sodium sulfate
15. concentrationconcentrated under reduced pressure
16. customThe resulting dark oil was purified by silica gel column chromatography
17. customAfter removing the solvent from the collected fractions, 5.880 g of pure (by HNMR analysis) product
18. customwas obtained
19. customThis material was recrystallized from ethyl acetate/hexane