Trimethylsilyl triflate → 1-[(2S,4R,5R)-4-acetoxy-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)tetrahydrofuran-2-yl]propyl benzoate

温度

70 °C

To a suspension of 5-amino-3,6-dihydrothiazolo[4,5-d]pyrimidine-2,7-dione (2.82 g, 16.8 mmol) in ACN (100 mL) was added BSA (10.4 mL, 42 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)-4,5-diacetoxytetrahydrofuran-2-yl]propyl benzoate (compound 26b, 4.9 g, 14.0 mmol) and TMSOTf (4.7 mL, 2.3 21 mmol) were added in sequence. After being heated with stirring 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. The residue was purified by column chromatography on silica gel (eluting with 1:200 methanol in DCM) to afford 5.27 g crude product of 1-[(2S,4R,5R)-4-acetoxy-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)tetrahydrofuran-2-yl]propyl benzoate (compound 26c) as a light yellow solid. MS obsd. (ESI+) [(M+H)+]: 475.

1. additionwas added BSA (10.4 mL, 42 mmol)
2. customThe resulting reaction mixture
3. customto form a clear solution
4. temperatureAfter the solution was cooled to room temperature
5. temperatureAfter being heated
6. stirringwith stirring at 70° C. for 14 hours
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 by column chromatography on silica gel (eluting with 1:200 methanol in DCM)

ORDレコード

ord-fa467a27fa8f49c1b9e0b6a922514cad

出典データセット

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09441008B2