反应详情

A solution of 8-Bromoadenosine (0.5 g, 1.5 mmol) and hexamethyldisilazane (5 mL) in 1,4-dioxane (10 mL) was heated overnight at 80° C. The reaction was cooled to room temperature, concentrated in vacuo, and azeotroped with toluene. The residue was taken up in NMP (3 mL) and tri-n-butylpropenyltin (1.0 g, 3.0 mmol) and Pd(PPh3)4 (0.175 g, 0.15 mmol) were added. The reaction was heated at 190° C. under microwave conditions for 0.5 h before cooling to room temperature. The catalyst was filtered through celite washing with EtOAc. The filtrate was partitioned between H2O and EtOAc. The aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was taken up in MeOH:H2O (4:1) (25 mL) and ammonium chloride was added (400 mg). The reaction was heated at 65° C. for 3 h. When judged complete by TLC, the reaction was concentrated in vacuo and was subjected to silica gel column chromatography running 0-25% MeOH:DCM with 0.1% NH4OH to afford 8-propenyl adenosine. The compound from the previous step was taken up in EtOH:H2O (3:1) (4 mL) and TFA (5 drops) and hydrogenated under H2 atmosphere in the presence of Pd/C 10% (20% w/w) at room temperature overnight. The catalyst was filtered off and the filtrate evaporated in vacuo. The 8-propyl adenosine was used without further purification.

1. concentrationconcentrated in vacuo
2. customazeotroped with toluene
3. temperatureThe reaction was heated at 190° C. under microwave conditions for 0.5 h
4. temperaturebefore cooling to room temperature
5. filtrationThe catalyst was filtered
6. washthrough celite washing with EtOAc
7. customThe filtrate was partitioned between H2O and EtOAc
8. extractionThe aqueous layer was extracted with EtOAc (2×20 mL)
9. washThe combined organic layers were washed with brine
10. dry with materialdried over MgSO4
11. concentrationconcentrated in vacuo
12. additionammonium chloride was added (400 mg)
13. temperatureThe reaction was heated at 65° C. for 3 h
14. concentrationthe reaction was concentrated in vacuo