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

HRID 60746Notes

Reaction equation

HRID 60746 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][C@H:22]([C@@H:25]1[CH2:29][C@@H:28]([CH3:30])[CH:27](OC(=O)C)[O:26]1)[CH2:23][CH3:24])(=[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][C@H:22]([C@@H:25]1[CH2:29][C@@H:28]([CH3:30])[C@H:27]([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:26]1)[CH2:23][CH3:24])(=[O:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1.[C:13]([O:21][C@@H:22]([C@@H:25]1[CH2:29][C@@H:28]([CH3:30])[C@H:27]([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:26]1)[CH2:23][CH3:24])(=[O:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 65367Trimethylsilyl triflateHCID 121396330[(1S)-1-[(2S,4R)-5-acetoxy-4-methyl-tetrahydrofuran-2-yl]propyl] benzoate2×HCID 1357436395-Aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione

Product 2

HCID 137108705[(1S)-1-[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-methyl-tetrahydrofuran-2-yl]propyl] benzoateHCID 137108750[(1R)-1-[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-methyl-tetrahydrofuran-2-yl]propyl] 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 (872 mg, 4.7 mmol) in ACN (20 mL) was added BSA (913.5 mg, 4.5 mmol). The resulting reaction mixture was then stirred at 70° C. under argon for 2 hours to form a clear solution. After the solution was cooled to room temperature, [(1S)-1-[(2S,4R)-5-acetoxy-4-methyl-tetrahydrofuran-2-yl]propyl] benzoate (compound 28j, 294 mg, 0.95 mmol) and TMSOTf (1.44 g, 6.6 mmol) were added in sequence. After being stirred with stirring at 20° C. for 14 hrs, 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 and separated by preparative HPLC to afford 9.7 mg of [(1S)-1-[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-methyl-tetrahydrofuran-2-yl]propyl] benzoate (compound 28k-A) and 8.4 mg of [(1R)-1-[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-methyl-tetrahydrofuran-2-yl]propyl] benzoate (compound 28k-B) as white solid.

Workup

  1. additionwas added BSA (913.5 mg, 4.5 mmol)
  2. customThe resulting reaction mixture
  3. customto form a clear solution
  4. temperatureAfter the solution was cooled to room temperature
  5. stirringAfter being stirred
  6. stirringwith stirring at 20° C. for 14 hrs
  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
  15. customseparated by preparative HPLC

Sources & evidence

ORD record
ord-cd593a6a6f8c4e0dab7eac3a93be4309
Source dataset
uspto-grants-2016_09
Patent number
US09441008B2

Reaction notes

Loading…