反应详情

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.29 g, 1.9 mmol) is added to 5,6-diamino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione (0.40 g, 1.9 mmol)) and (1-chloro-6,7-dimethoxy-isoquinolin-4-yl)-acetic acid (0.39 g, 1.78 mmol) in methanol and water and the mixture is stirred at ambient temperature for 2 hours. The methanol is evaporated and the resultant solid collected by filtration and recrystalised from ethylacetate/methanol. The resulting solid is heated under reflux with piperidine for 8 h. The solution is filtered and the resulting solution washed with water and brine, dried over sodium sulphate, filtered and concentrated. Further purification by flash silica column chromatography (eluant: ethylacetate/methanol) yields a solid which is dissolved 20% 1N NaOH/methanol and heated to reflux for 2 h. Concentration, addition of water and extraction with ethyl acetate gives an organic fraction which is washed with water and brine, dried over Na2SO4, filtered and concentrated to give 8-(6,7-dimethoxy-1-piperidin-1-yl-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione, MH+ 507.

1. customThe methanol is evaporated
2. filtrationthe resultant solid collected by filtration
3. customrecrystalised from ethylacetate/methanol
4. temperatureThe resulting solid is heated
5. temperatureunder reflux with piperidine for 8 h
6. filtrationThe solution is filtered
7. washthe resulting solution washed with water and brine
8. dry with materialdried over sodium sulphate
9. filtrationfiltered
10. concentrationconcentrated
11. customFurther purification by flash silica column chromatography (eluant: ethylacetate/methanol)
12. customyields a solid which
13. temperatureheated
14. temperatureto reflux for 2 h
15. concentrationConcentration, addition of water and extraction with ethyl acetate
16. customgives an organic fraction which
17. washis washed with water and brine
18. dry with materialdried over Na2SO4
19. filtrationfiltered
20. concentrationconcentrated