Trimethylsilyl triflate → HCID 11675322, compound

HRID 392902Notes

Reaction equation

HRID 392902 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[NH:4][CH:5]=[N:6]2.[CH3:11][NH:12][C:13](=[O:30])[C@H:14]1[O:22][CH:17](OC(=O)C)[C@H:16]([O:23][C:24](=[O:26])[CH3:25])[C@@H:15]1[N:27]=[N+:28]=[N-:29].[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>C[Si](C)(C)N[Si](C)(C)C.ClC(Cl)C>[CH3:11][NH:12][C:13]([C@@H:14]1[C@@H:15]([N:27]=[N+:28]=[N-:29])[C@@H:16]([O:23][C:24](=[O:26])[CH3:25])[C@H:17]([N:6]2[CH:5]=[N:4][C:3]3[C:7]2=[N:8][CH:9]=[N:10][C:2]=3[Cl:1])[O:22]1)=[O:30]

Participants

6

Reactant 3

HCID 65367Trimethylsilyl triflateHCID 53592776-ChloropurineHCID 11652147HCID 11652147, compound

Product 1

HCID 11675322HCID 11675322, compoundYield 63.3%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 13838HexamethyldisilazaneSolvent

Conditions

Temperature
110 °C

Procedure

6-Chloropurine (20.4 g, 0.132 mol) was suspended in hexamethyl disilazane (165 mL) and heated at 110° C. After 2 h, the now homogeneous mixture was concentrated and the solid residue reconcentrated from toluene 2× and placed under high vac for 1 hour. The resulting solid was combined with 1,2-bis-O-acetyl-3-azido-3-deoxy-D-ribofuranuronic acid methyl amide (12.7 g, 0.044 mol) and dissolved in anhydrous dichloroethane (350 mL). Powdered 4A molecular sieves (15 g) were added and the mixture stirred for 15 minutes. TMSOTf (16.0 mL, 0.088 mol) was added and the reaction was then heated to 60° C. for two hours, cooled and quenched by the careful addition of saturated sodium bicarbonate solution (200 mL). Ethyl acetate (350 mL) was added and the mixture was filtered through sintered glass. The filtrate was extracted with ethyl acetate (3×) and the combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (15% then 20% acetone/dichloromethane) to afford the title compound (10.6 g) as an off-white foam. MS 381 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.8 (s, 1H); 8.2 (s, 1H); 7.6 (bs, 1H); 6.13 (d, 1H, J=7.0 Hz); 5.87 (dd, 1H, J=7.0, 5.6 Hz); 4.85 (dd, 1H, J=5.6, 3.0 Hz); 4.58 (d, 1H, J=3.0 Hz); 2.9 (d, 1H, J=4.9 Hz); 2.11 (s, 3H).

Workup

  1. concentrationthe now homogeneous mixture was concentrated
  2. waitplaced under high vac for 1 hour
  3. temperaturethe reaction was then heated to 60° C. for two hours
  4. temperaturecooled
  5. customquenched by the careful addition of saturated sodium bicarbonate solution (200 mL)
  6. additionEthyl acetate (350 mL) was added
  7. filtrationthe mixture was filtered through sintered glass
  8. extractionThe filtrate was extracted with ethyl acetate (3×)
  9. washthe combined organic layers were washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by flash chromatography (15%

Sources & evidence

ORD record
ord-ee3dedee18594c43a69f2028a5c9c852
Source dataset
uspto-grants-2004_10
Patent number
US06803457B1

Reaction notes

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