反应详情

Ethoxyacetyl chloride (1.78 g, 14.6 mmol) was added dropwise to a 0° C. solution of 1-{[(3-amino[1,5]naphthyridin-4-yl)amino]methyl}cyclohexanol (prepared as described in Part B of Example 57, 13.2 mmol) in dichloromethane (90 mL). After 1.5 h, more ethoxyacetyl chloride (0.3 mL) was added and stirring was continued for another 30 min. More ethoxyacetyl chloride (0.4 mL) was added and stirring was continued overnight. The solvent was removed under reduced pressure and the residue was dissolved in ethanol (90 mL). Sodium hydroxide (1.06 g, 26.5 mmol) was added and the reaction was heated at reflux for about 1 d. The solvent was removed under reduced pressure and the residue was partitioned between dichloromethane (200 mL) and water (100 mL). The aqueous phase was extracted with dichloromethane (2×100 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to yield a brown foam. The foam was triturated with ethyl acetate and sonicated briefly. A white solid was isolated by filtration. The filtrate was concentrated and the trituration process was repeated two more times. The off white solids were combined and dried to yield 1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]methyl}cyclohexanol (3.40 g, 76% over three steps).

1. waitwas continued for another 30 min
2. stirringstirring
3. waitwas continued overnight
4. customThe solvent was removed under reduced pressure
5. dissolutionthe residue was dissolved in ethanol (90 mL)
6. temperaturethe reaction was heated
7. temperatureat reflux for about 1 d
8. customThe solvent was removed under reduced pressure
9. customthe residue was partitioned between dichloromethane (200 mL) and water (100 mL)
10. extractionThe aqueous phase was extracted with dichloromethane (2×100 mL)
11. washThe combined organic layers were washed with brine (50 mL)
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customto yield a brown foam
16. customThe foam was triturated with ethyl acetate
17. customsonicated briefly
18. customA white solid was isolated by filtration
19. concentrationThe filtrate was concentrated
20. customdried