反应详情

2-(Ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-amine (0.900 g, 3.71 mmol) was placed in a 50 mL round bottom flask, dissolved in 1,2-dichloromethane, and placed under N2. Cyclohexanone (1.19 mL, 11.5 mmol), acetic acid (0.45 mL, 7.79 mmol) and sodium triacetoxyborohydride (1.65 g, 7.79 mmol) were added and the reaction was stirred under N2 at room temperature for 5 days. The reaction was quenched by slow addition of saturated NaHCO3 solution (25 mL) and dichloromethane (25 mL). The mixture was transferred to a separatory funnel and the phases separated. The aqueous portion was extracted with dichloromethane (25 mL). The combined organic portions were washed sequentially with water (25 mL) and brine (25 mL), dried (Na2SO4), filtered and then concentrated to yield a thick brown oil. Analysis by liquid chromatography/mass spectroscopy (LC/MS) of the crude product showed it to be a mixture of the hydrazone and hydrazine. The oil was dissolved in methanol (25 mL), chilled in an ice water bath and then treated with sodium borohydride (1.25 g). The reaction was quenched with water (25 mL) and the mixture concentrated. The residue was partitioned between dichloromethane 50 mL) and water (15 mL), transferred to a separatory funnel, and the phases were separated. The organic portion was washed sequentially with saturated NaHCO3 solution (20 mL), water (20 mL) and brine (20 mL), dried (Na2SO4), filtered and then concentrated to yield a thick brown oil. The material was purified by column chromatography (35 g SiO2, 97:3 chloroform:methanol) to yield 0.51 g of N-cyclohexyl-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-amine as a light brown oil/solid.

1. customThe reaction was quenched by slow addition of saturated NaHCO3 solution (25 mL) and dichloromethane (25 mL)
2. customThe mixture was transferred to a separatory funnel
3. customthe phases separated
4. extractionThe aqueous portion was extracted with dichloromethane (25 mL)
5. washThe combined organic portions were washed sequentially with water (25 mL) and brine (25 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto yield a thick brown oil
10. temperaturechilled in an ice water bath
11. customThe reaction was quenched with water (25 mL)
12. concentrationthe mixture concentrated
13. customThe residue was partitioned between dichloromethane 50 mL) and water (15 mL)
14. customtransferred to a separatory funnel
15. customthe phases were separated
16. washThe organic portion was washed sequentially with saturated NaHCO3 solution (20 mL), water (20 mL) and brine (20 mL)
17. dry with materialdried (Na2SO4)
18. filtrationfiltered
19. concentrationconcentrated
20. customto yield a thick brown oil
21. customThe material was purified by column chromatography (35 g SiO2, 97:3 chloroform:methanol)