反应详情

To a suspension of 395 g (1.12 moles) of 9-benzyl-1,3-dimethyl-6-hydroxy-pyrimido[2,1-f]purine-2,4,8(1H,3H,9H)-trione in 10.5 liters of dry 1,4-dioxan, add 68.1 g (3.14 moles) of lithium borohydride in portions. Maintain the reaction temperature at 20°-25° C. by controlling the rate of addition and by use of a cooling bath as needed. Stir the mixture at room temperature for 0.5 hour, then reflux for 18 hours. Remove a portion of the solvent under reduced pressure, and purge the system with nitrogen as the vacuum is released. Allow the residue to cool; then add 4.5 liters of chloroform. To the resultant mixture, cautiously add dropwise 1.1-liters of water. Stir the mixture at room temperature until two clear phases result. Add 3N hydrochloric acid portionwise to bring the pH to 4-5. Separate the layers, and extract the aqueous phase with two 1.1-liter portions of chloroform. Wash the combined extracts with three 1.1 liter volumes of water, and dry over anhydrous sodium sulfate. Filter off the drying agent, and remove volatiles from the filtrate under reduced pressure. Crystallize the residue from methanolethyl acetate to obtain title compound (I) as a solid with mp 176°-182° C.

1. temperatureMaintain the reaction temperature at 20°-25° C.
2. additionthe rate of addition
3. customby use of a cooling bath as needed
4. temperaturereflux for 18 hours
5. customRemove a portion of the solvent under reduced pressure
6. custompurge the system with nitrogen as the vacuum
7. temperatureto cool
8. additionthen add 4.5 liters of chloroform
9. additionTo the resultant mixture, cautiously add dropwise 1.1-liters of water
10. stirringStir the mixture at room temperature until two clear phases
11. customresult
12. customSeparate the layers
13. extractionextract the aqueous phase with two 1.1-liter portions of chloroform
14. washWash the combined extracts with three 1.1 liter volumes of water
15. dry with materialdry over anhydrous sodium sulfate
16. filtrationFilter off the drying agent
17. customremove volatiles from the filtrate under reduced pressure
18. customCrystallize the residue from methanolethyl acetate