反应详情

温度

55 °C

To 3-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (6.0 g, 21.24 mmol) in dry DMF (100 ml) was added Cs2CO3 (7.62 g, 23.36 mmol) followed by ethyl 4-bromobutyrate (4.556 g, 23.36 mmol). The mixture was heated at 55° C. for 18 h and allowed to cool then degassed by repeatedly evacuating and readmitting nitrogen. Morpholine (14.9 g, 171 mmol) was added followed by tetrakis(triphenylphosphine)palladium(0) (4.0 g, 3.46 mmol) and the mixture was stirred for 4 h. EtOAc (300 ml) and 2M HCl (150 ml) and water (100 ml) were added and the organic phase separated, washed with brine (3×100 ml) and filtered. The filtrate was dried (Na2SO4) and evaporated. The crude product (10 g) was purified by aminopropyl SPE (3×20 g), loading in THF/MeOH (1:1), washing with THF/MeOH (1:1) and neat MeOH and eluting the product with DCM/MeOH (1:1) containing 5% added AcOH to afford the title compound (5.08 g).

1. temperatureto cool
2. customthen degassed
3. customby repeatedly evacuating
4. customthe organic phase separated
5. washwashed with brine (3×100 ml)
6. filtrationfiltered
7. dry with materialThe filtrate was dried (Na2SO4)
8. customevaporated
9. customThe crude product (10 g) was purified by aminopropyl SPE (3×20 g)
10. washwashing with THF/MeOH (1:1) and neat MeOH
11. washeluting the product with DCM/MeOH (1:1)
12. additioncontaining 5%
13. additionadded AcOH