Trimethylsilyl triflate → 5-Aza-2'-deoxycytidine

HRID 1777284Notes

Reaction equation

HRID 1777284 reaction equation
FC(F)(F)C(=N[Si](C)(C)C)O[Si](C)(C)C.[NH:16]1[CH:23]=[N:22][C:20]([NH2:21])=[N:19][C:17]1=[O:18].C[Si](OS(C(F)(F)F)(=O)=O)(C)C.Cl[C:37]1([O:43][C@H:42]([CH:44](C(C2C=CC(C)=CC=2)=O)[OH:45])[C@@:40](C(C2C=CC(C)=CC=2)=O)([OH:41])[CH2:39]1)O.C[O-].[Na+]>C(#N)C.CO>[CH2:39]1[C@H:37]([N:16]2[C:17](=[O:18])[N:19]=[C:20]([NH2:21])[N:22]=[CH:23]2)[O:43][C@H:42]([CH2:44][OH:45])[C@H:40]1[OH:41]

Participants

8

Reactant 5

HCID 65367Trimethylsilyl triflateHCID 94358Bis(trimethylsilyl)trifluoroacetamideHCID 10942334Sodium MethoxideHCID 674207861-chloro-3,5-di-p-toluoyl-2-deoxy-D-ribofuranoseHCID 178508820HCID 178508820, compound

Product 1

HCID 4516685-Aza-2'-deoxycytidineYield 36.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 6342AcetonitrileSolvent

Procedure

34 mL of BSTFA are added to a suspension of 6.4 g of azacytosine in 300 mL of acetonitrile. The mixture is brought to 50° C. and it is stirred for 90 minutes. It is cooled to ambient temperature, 6.3 mL of trimethylsilyltriflate and 11.1 g of 1-chloro-3,5-di-p-toluoyl-2-deoxy-D-ribofuranose are added to the solution, in about ten minutes. It is stirred for 140 minutes, 400 mL of methanol are added controlling the temperature in an ice bath. Concentration is carried out at low pressure until a viscous residue is obtained, 400 mL of methanol are added, it is heated to 50° C. and 36 mL of 30% solution of sodium methylate in methanol are added. It is stirred for 1 hour, it is cooled to 0° C., it is stirred to complete precipitation and the solid is filtered by washing it on the filter with methanol. 2.3 g of decitabine with HPLC purity (UV 254 nm) of 99.2% are obtained after drying at low pressure.

Workup

  1. customis brought to 50° C.
  2. stirringIt is stirred for 140 minutes
  3. concentrationConcentration
  4. customis obtained
  5. temperatureit is heated to 50° C.
  6. stirringIt is stirred for 1 hour
  7. temperatureit is cooled to 0° C.
  8. stirringit is stirred to complete precipitation
  9. filtrationthe solid is filtered
  10. washby washing it on the
  11. filtrationfilter with methanol

Sources & evidence

ORD record
ord-208bd4b0488f4fc3b89b3c2da543ecc0
Source dataset
uspto-grants-2016_02
Patent number
US09266863B2

Reaction notes

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