反应详情

温度

150 °C

1-[2,6,7-Trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]eth-2-yl (3-phenylprop-2-ynyl) ether (5.4 g, 13.122 mmol) from Part H and ammonium acetate (54 g) were combined in a glass pressure vessel. The vessel was sealed with a teflon screw cap, and the reaction mixture was heated to 150° C. for 45 hours. The reaction was essentially complete, and the resulting reaction solution was cooled with an ice bath, acidified to a pH of 1 with 10% hydrochloric acid, and washed with dichloromethane (3×500 mL). The combined organic portions were washed with 10% hydrochloric acid (4×). The acidic aqueous portions were combined, basified with potassium hydroxide pellets to a pH of 14. The resulting brown solids were filtered off and recrystallized from methanol. A first crop of 0.6 g was collected for use in Example 5, and a second crop was collected and found to contain about 2% of the 4-hydroxy compound by NMR analysis. The second crop was returned to the mother liquor, and dichloromethane was added until all solids were dissolved. 1M Hydrochloric acid in diethyl ether (20 mL) was added to the resulting solution, and the solids that formed were filtered off, and dissolved in water, which was basified to a pH of 14 with potassium hydroxide pellets. The resulting solution was washed with dichloromethane (3×). The organic portions were combined, washed with water (2×) and brine (2×), dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting white solid (1.8 g) was dissolved in dichloromethane (150 mL), and 1M hydrochloric acid in diethyl ether (5.3 mL) was added to the resulting solution. The acidified solution was concentrated under reduced pressure. The resulting solids were dissolved in water, and this aqueous solution was filtered to remove an oily sludge. The filtrate was basified with a few drops of 20% potassium hydroxide and then 1N potassium hydroxide to a pH of 13. The fine white precipitate that formed was filtered off, rinsed with diethyl ether, and dried under vacuum for 18 hours to provide 1.8064 g of 2,6,7-trimethyl-1-{2-[(3-phenylprop-2-ynyl)oxy]ethyl}-1H-imidazo[4,5-c]pyridin-4-amine, m.p. 186.8–187.5° C.

1. customscrew cap
2. customthe resulting reaction solution
3. temperaturewas cooled with an ice bath
4. washwashed with dichloromethane (3×500 mL)
5. washThe combined organic portions were washed with 10% hydrochloric acid (4×)
6. filtrationThe resulting brown solids were filtered off
7. customrecrystallized from methanol
8. customA first crop of 0.6 g was collected for use in Example 5
9. customa second crop was collected
10. additionwas added until all solids
11. dissolutionwere dissolved
12. addition1M Hydrochloric acid in diethyl ether (20 mL) was added to the resulting solution
13. customthe solids that formed
14. filtrationwere filtered off
15. dissolutiondissolved in water
16. washThe resulting solution was washed with dichloromethane (3×)
17. washwashed with water (2×) and brine (2×)
18. dry with materialdried with magnesium sulfate
19. filtrationfiltered
20. concentrationconcentrated under reduced pressure
21. dissolutionThe resulting white solid (1.8 g) was dissolved in dichloromethane (150 mL)
22. addition1M hydrochloric acid in diethyl ether (5.3 mL) was added to the resulting solution
23. concentrationThe acidified solution was concentrated under reduced pressure
24. dissolutionThe resulting solids were dissolved in water
25. filtrationthis aqueous solution was filtered
26. customto remove an oily sludge
27. customThe fine white precipitate that formed
28. filtrationwas filtered off
29. washrinsed with diethyl ether
30. customdried under vacuum for 18 hours