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 in a sealed tube (100° C., 8 h) with 40% aqueous dimethylamine. The mixture is evaporated and extracted with ethylacetate. The ethylacetate solution is then washed with water and brine, dried over sodium sulphate, filtered and concentrated. Further purification by flash silica column chromatography (eluant: ethylacetate/methanol) yields 8-(1-dimethylamino-6,7-dimethoxy-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione, MH+ 467.

1. customThe methanol is evaporated
2. filtrationthe resultant solid collected by filtration
3. customrecrystalised from ethylacetate/methanol
4. temperatureThe resulting solid is heated in a sealed tube (100° C., 8 h) with 40% aqueous dimethylamine
5. customThe mixture is evaporated
6. extractionextracted with ethylacetate
7. washThe ethylacetate solution is then 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)