Trimethylsilyl triflate → 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

HRID 60727Notes

Reaction equation

HRID 60727 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][CH:22]([C@@H:24]1[CH2:28][C@@H:27]([N:29]=[N+:30]=[N-:31])[CH:26](OC)[O:25]1)[CH3:23])(=[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][CH:22]([C@@H:24]1[CH2:28][C@@H:27]([N:29]=[N+:30]=[N-:31])[C@H:26]([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:25]1)[CH3:23])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 65367Trimethylsilyl triflateHCID 1213963101-[(2S,4R)-4-azido-5-methoxy-tetrahydrofuran-2-yl]ethyl benzoate2×HCID 1357436395-Aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione

Product 1

HCID 1371087471-[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-azido-tetrahydrofuran-2-yl]ethyl benzoateYield 135.3%

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 (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.

Workup

  1. additionwas added BSA (630 mg, 3 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 at 70° C. for 14 hours
  6. customthe solvent was removed in vacuo
  7. customThe residue was partitioned between EtOAc and saturated NaHCO3 solution (30 mL)
  8. customThe organic layer was separated
  9. extractionthe aqueous phase was extracted with EtOAc (30 mL) twice
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1a5264f6007c4e27a466706e68b89a45
Source dataset
uspto-grants-2016_09
Patent number
US09441008B2

Reaction notes

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