反应详情

温度

70 °C

To a suspension of 5-amino-3,6-dihydrothiazolo[4,5-d]pyrimidine-2,7-dione (872 mg, 4.7 mmol) in ACN (20 mL) was added BSA (913.5 mg, 4.5 mmol). The resulting reaction mixture was then stirred at 70° C. under argon for 2 hours to form a clear solution. After the solution was cooled to room temperature, [(1S)-1-[(2S,4R)-5-acetoxy-4-methyl-tetrahydrofuran-2-yl]propyl] benzoate (compound 28j, 294 mg, 0.95 mmol) and TMSOTf (1.44 g, 6.6 mmol) were added in sequence. After being stirred with stirring at 20° C. for 14 hrs, the solvent was removed in vacuo. The residue was partitioned between EtOAc and saturated NaHCO3 solution (30 mL). The organic layer was separated and the aqueous phase was extracted with EtOAc (30 mL) twice. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified and separated by preparative HPLC to afford 9.7 mg of [(1S)-1-[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-methyl-tetrahydrofuran-2-yl]propyl] benzoate (compound 28k-A) and 8.4 mg of [(1R)-1-[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-methyl-tetrahydrofuran-2-yl]propyl] benzoate (compound 28k-B) as white solid.

1. additionwas added BSA (913.5 mg, 4.5 mmol)
2. customThe resulting reaction mixture
3. customto form a clear solution
4. temperatureAfter the solution was cooled to room temperature
5. stirringAfter being stirred
6. stirringwith stirring at 20° C. for 14 hrs
7. customthe solvent was removed in vacuo
8. customThe residue was partitioned between EtOAc and saturated NaHCO3 solution (30 mL)
9. customThe organic layer was separated
10. extractionthe aqueous phase was extracted with EtOAc (30 mL) twice
11. washThe combined organic layers were washed with brine
12. dry with materialdried over Na2SO4
13. concentrationconcentrated in vacuo
14. customThe residue was purified
15. customseparated by preparative HPLC