反応 #89005

ord-1a5264f6007c4e27a466706e68b89a45

溶媒

反応条件

温度
70°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    workup.ADDITIONwas added BSA (630 mg, 3 mmol)
  2. 2
    その他The resulting reaction mixture
  3. 3
    その他to form a clear solution
  4. 4
    温度After the solution was cooled to room temperature
  5. 5
    温度After being heated at 70° C. for 14 hours
  6. 6
    その他the solvent was removed in vacuo
  7. 7
    その他The residue was partitioned between EtOAc and saturated NaHCO3 solution (30 mL)
  8. 8
    その他The organic layer was separated
  9. 9
    抽出the aqueous phase was extracted with EtOAc (30 mL) twice
  10. 10
    洗浄The combined organic layers were washed with brine
  11. 11
    乾燥dried over Na2SO4
  12. 12
    濃縮concentrated in vacuo

実験手順

To a suspension of 5-amino-3,6-dihydrothiazolo[4,5-d]pyrimidine-2,7-dione (186 mg, 1 mmol) in ACN (10 mL) was added BSA (630 mg, 3 mmol). The resulting reaction mixture was then stirred at 70° C. under argon for 0.5 hour to form a clear solution. After the solution was cooled to room temperature, 1-[(2S,4R)-4-azido-5-methoxy-tetrahydrofuran-2-yl]ethyl benzoate (compound 25k, 300 mg, 1.0 mmol) and TMSOTf (1.15 g, 5 mmol) were added in sequence. After being heated at 70° C. for 14 hours, 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 to afford 600 mg crude product of 1-[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-azido-tetrahydrofuran-2-yl]ethyl benzoate (compound 25l), which was used in next step without further purification. MS obsd. (ESI+) [(M+H)+]: 442.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US09441008B2uspto-grants-2016_09