Trimethylsilyl triflate → HCID 16735277, compound

HRID 1474750Notes

Reaction equation

HRID 1474750 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([Cl:11])[N:3]=1.S([O-])([O-])(=O)=O.[NH4+].[NH4+].C(O[C@H:23]1[C@H:30]2[C@H:26]([O:27][C:28]([CH3:32])([CH3:31])[O:29]2)[CH2:25][S:24]1)(=O)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O>C[Si](C)(C)N[Si](C)(C)C.ClC=CCl.ClCCCl.ClCCl>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@H:23]2[C@H:30]3[C@H:26]([O:27][C:28]([CH3:32])([CH3:31])[O:29]3)[CH2:25][S:24]2)=[C:4]([Cl:11])[N:3]=1

Participants

9

Reactant 4

HCID 65367Trimethylsilyl triflateHCID 53244122,6-DichloropurineHCID 6097028Ammonium SulfateHCID 68597674HCID 68597674, compound

Product 1

HCID 16735277HCID 16735277, compoundYield 79%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 109001,2-DichloroethyleneSolventHCID 13838HexamethyldisilazaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2,6-dichloropurine (2.29 g, 22.12 mmol) and ammonium sulfate (438 mg, 3.32 mmol) in hexamethyldisilazane (HMDS, 50 ml) was fluxed overnight under inert, dry conditions. The resulting reaction mixture was concentrated in a vacuum and the solid mixture thus formed was re-dissolved in cold 1,2-dichloroethene (20 ml). To this solution were dropwise added a solution of (3aR,4R,6aS)-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-yl acetate (1.41 g, 11.06 mmol), obtained in Preparation Example 1, in 1,2-dichloroethane (20 ml), and then trimethylsilyl trifluoromethanesulfonate (TMSOTf, 4.0 ml, 22.12 mmol). The resulting solution was stirred at 0° C. for 30 min and then at room temperature for 1 hr, and heated at 80° C. for 2 hrs with stirring. The reaction mixture was cooled, diluted in dichloromethane and washed with a saturated aqueous sodium hydrogen carbonate (NaHCO3) solution. The organic solvent was dried over anhydrous magnesium sulfate (MgSO4) and concentrated in a vacuum to give a residue in the form of a yellow syrup. The residue was purified through silica gel column chromatography using a mixture of dichloromethane:methanol (50:1, v/v) as an elution solvent to afford the object compound in the form of a foam (3.03 g, 79%).

Workup

  1. customunder inert, dry conditions
  2. customThe resulting reaction mixture
  3. concentrationwas concentrated in a vacuum
  4. customthe solid mixture thus formed
  5. waitat room temperature for 1 hr
  6. temperatureheated at 80° C. for 2 hrs
  7. stirringwith stirring
  8. temperatureThe reaction mixture was cooled
  9. washwashed with a saturated aqueous sodium hydrogen carbonate (NaHCO3) solution
  10. dry with materialThe organic solvent was dried over anhydrous magnesium sulfate (MgSO4)
  11. concentrationconcentrated in a vacuum
  12. customto give a residue in the form of a yellow syrup
  13. customThe residue was purified through silica gel column chromatography
  14. additiona mixture of dichloromethane:methanol (50:1

Sources & evidence

ORD record
ord-42423405cc8d464f84dc1b8db64aa02e
Source dataset
uspto-grants-2015_04
Patent number
US09018371B2

Reaction notes

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