反应详情

A solution of 6.2 g (0.02 mole) of crude N-(6-chlorohexyl)-6-methoxy-4-methyl-8-quinolinamine in 75 ml of toluene was added dropwise to a stirred, hot suspension of 25 g (0.29 mole) of piperazine in 25 ml of toluene. The mixture was distilled until the internal temperature rose to 130°, allowed to cool, and taken up in a mixture of water and dichloromethane. The organic layer was separated, washed again, dried over anhydrous magnesium sulfate and concentrated to dryness in vacuo. The residual brown oil was chromatographed over 200 g of silica gel first with ethyl acetate and then with 500 ml each of the following solutions of methanol in ethyl acetate: 4%, 8%, 12% 16%, 20% and 25%. The eluant which appeared to contain only the product, Rf (silica--25 methanol:75 ethyl acetate:1 triethylamine)=0.05 was concentrated to dryness in vacuo. The residue was triturated with ether and filtered to remove 1 g of the bis product, mp 126°-128°, and concentrated again. The residue was dissolved in hot 2-propanol, filtered to remove haze and treated with a saturated solution of hydrogen chloride in 2-propanol. The resulting precipitate was collected, dried overnight at 60° in vacuo and allowed to air-equilibrate to afford 5.8 (60% ) of the title compound, mp 245°-247° (dec) with prior sintering at 125°. The NMR spectrum confirmed the presence of 2-propanol.

1. distillationThe mixture was distilled until the internal temperature
2. customrose to 130°
3. temperatureto cool
4. additiontaken up in a mixture of water and dichloromethane
5. customThe organic layer was separated
6. washwashed again
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated to dryness in vacuo
9. customThe residual brown oil was chromatographed over 200 g of silica gel first with ethyl acetate
10. concentrationwas concentrated to dryness in vacuo
11. customThe residue was triturated with ether
12. filtrationfiltered
13. customto remove 1 g of the bis product, mp 126°-128°
14. concentrationconcentrated again
15. dissolutionThe residue was dissolved in hot 2-propanol
16. filtrationfiltered
17. customto remove haze
18. additiontreated with a saturated solution of hydrogen chloride in 2-propanol
19. customThe resulting precipitate was collected
20. customdried overnight at 60° in vacuo