Trifluoromethanesulfonic anhydride → 3'-Azido-ddA

HRID 2258066Notes

Reaction equation

HRID 2258066 reaction equation
C([NH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[C@@H:19]1[O:24][C@H:23]([CH2:25][O:26]C(=O)C2C=CC=CC=2)[C@H:21](O)[CH2:20]1)(=O)C1C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[N-:50]=[N+:51]=[N-:52].[Li+]>CN(C=O)C.C(Cl)(Cl)Cl.O.ClCCl.N1C=CC=CC=1>[N:50]([C@@H:21]1[C@@H:23]([CH2:25][OH:26])[O:24][C@@H:19]([N:14]2[C:15]3[N:16]=[CH:17][N:18]=[C:10]([NH2:9])[C:11]=3[N:12]=[CH:13]2)[CH2:20]1)=[N+:51]=[N-:52]

Participants

9

Reactant 3

HCID 67749Trifluoromethanesulfonic anhydrideHCID 88163Lithium azideHCID 13964206HCID 13964206, compound

Product 1

HCID 4513623'-Azido-ddAYield 80%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 920 mg (2 mmol) of N6 -benzoyl-9-(5-O-benzoyl-2-deoxy-β-D-threopentofuranosyl)-adenine in 20 ml of abs. dichloromethane (and 2 ml of pyridine) is cooled to -30° C. Then 5 ml (3 mmol) of a solution of trifluoromethanesulfonic anhydride in abs. dichloromethane are added dropwise. The cooling bath is removed, the mixture is stirred for a further 20 min, and 980 mg (20 mmol) of lithium azide in 20 ml of DMF are added to the solution. After stirring at RT for a further 2 h, 50 ml of water and 150 ml of chloroform are added, and the organic phase is taken up and washed with distilled water. The solvent is removed in a ®Rotavapor and the product is treated with ammoniacal methanol solution overnight to remove the base protective group. Renewed removal of solvent is followed by purification by flash chromatography (chloroform:methanol 95:5) on silica gel. Yields 430 mg (1.6 mmol, 79%) of white crystalline powder. IR: 2,100 cm-1 azido group.

Workup

  1. customThe cooling bath is removed
  2. stirringAfter stirring at RT for a further 2 h
  3. washwashed with distilled water
  4. customThe solvent is removed in a ®Rotavapor
  5. additionthe product is treated with ammoniacal methanol solution overnight
  6. customto remove the base protective group
  7. customremoval of solvent
  8. customis followed by purification by flash chromatography (chloroform:methanol 95:5) on silica gel

Sources & evidence

ORD record
ord-1253b2db1c724465840f07ef2fcf136b
Source dataset
uspto-grants-1997_08
Patent number
US05659025

Reaction notes

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