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

HRID 60753Notes

Reaction equation

HRID 60753 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]([N:28]=[N+:29]=[N-:30])[C@H:25](OC)[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]([N:28]=[N+:29]=[N-: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 121396352[(2S,4R,5R)-4-azido-5-methoxy-tetrahydrofuran-2-yl]methyl benzoate2×HCID 1357436395-Aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione

Product 1

HCID 137108723[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-azido-tetrahydrofuran-2-yl]methyl benzoateYield 29.3%

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 (730 mg, 3.97 mmol) in ACN (15 mL) was added BSA (2.8 mg, 13.8 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, [(2S,4R,5R)-4-azido-5-methoxy-tetrahydrofuran-2-yl]methyl benzoate (compound 33a, crude, 1.1 g, 3.97 mmol) and TMSOTf (4.4 g, 19.5 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 to afford 500 mg crude product of [(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-azido-tetrahydrofuran-2-yl]methyl benzoate (compound 33b) as a yellow solid. MS obsd. (ESI+) [(M+H)+]: 430.

Workup

  1. additionwas added BSA (2.8 mg, 13.8 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

Sources & evidence

ORD record
ord-aa541459ad8a44a69800d47e6a1ec76c
Source dataset
uspto-grants-2016_09
Patent number
US09441008B2

Reaction notes

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