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

HRID 60757Notes

Reaction equation

HRID 60757 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=[O:12])[C:5]2[S:10][C:9](=[O:11])[NH:8][C:6]=2[N:7]=1.[C:13]([O:21][CH2:22][C@@H:23]1[CH2:27][C@@H:26]([O:28][C:29](=[O:31])[CH3:30])[CH:25](OC(=O)C)[O:24]1)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>C(#N)C>[C:13]([O:21][CH2:22][C@@H:23]1[CH2:27][C@@H:26]([O:28][C:29](=[O:31])[CH3:30])[C@H:25]([N:8]2[C:6]3[N:7]=[C:2]([NH2:1])[NH:3][C:4](=[O:12])[C:5]=3[S:10][C:9]2=[O:11])[O:24]1)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 65367Trimethylsilyl triflateHCID 147571015-O-Benzoyl-1,2-di-O-acetyl-3-deoxy-D-ribofuranoseHCID 1357436395-Aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione

Product 1

HCID 137108751[(2S,4R,5R)-4-acetoxy-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)tetrahydrofuran-2-yl]methyl benzoate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of 5-amino-3,6-dihydrothiazolo[4,5-d]pyrimidine-2,7-dione (4.42 g, 24.0 mmol) in ACN (20 mL) was added BSA (14.8 mL, 60.0 mmol). The resulting reaction mixture was then stirred at 70° C. under argon for 0.5 hr to form a clear solution. After the solution was cooled to room temperature, [(2S,4R)-4,5-diacetoxytetrahydrofuran-2-yl]methyl benzoate (CAS #: 4613-71-2, Cat.#: MD04725, commercially available from Carbosynth Limited, 6.45 g, 20.0 mmol) and TMSOTf (5.5 mL, 30.0 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 (100 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 to afford 5.7 g of [(2S,4R,5R)-4-acetoxy-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)tetrahydrofuran-2-yl]methyl benzoate (compound 38a) as a light yellow solid.

Workup

  1. additionwas added BSA (14.8 mL, 60.0 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 (100 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

Sources & evidence

ORD record
ord-46ce9246d3304875966a6068ba677d9c
Source dataset
uspto-grants-2016_09
Patent number
US09441008B2

Reaction notes

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