Methanol → 1-(4-amino-5-iodo-2-oxo-1H-pyrimidin-1-yl)-2-desoxy-2,2-difluororibose

HRID 128567Notes

Reaction equation

HRID 128567 reaction equation
O([C@:9]([C@@H:21]([CH:23]([O:25][Si](C(C)(C)C)(C)C)O)[OH:22])([OH:20])[C:10]([F:19])([F:18])[C:11]([O:13]S(C)(=O)=O)=O)[Si](C(C)(C)C)(C)C.C[Si]([N:37]([Si](C)(C)C)[C:38]1[C:43]([I:44])=[CH:42][N:41]([Si](C)(C)C)[C:40](=[O:49])[N:39]=1)(C)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.CO>ClCCCl>[NH2:37][C:38]1[C:43]([I:44])=[CH:42][N:41]([C:11]([C:10]([F:18])([F:19])[C@@H:9]([C@@H:21]([CH2:23][OH:25])[OH:22])[OH:20])=[O:13])[C:40](=[O:49])[N:39]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 65367Trimethylsilyl triflateHCID 18598562HCID 18598562, compoundHCID 67917102Tris-trimethylsilyl-5-iodocytosine

Product 1

HCID 185985421-(4-amino-5-iodo-2-oxo-1H-pyrimidin-1-yl)-2-desoxy-2,2-difluororiboseYield 1.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To 1.99 g (0.0042 mol) of 3,5-bis(t-butyldimethylsiloxy)-1-methanesulfonyloxy-2-desoxy-2,2-difluororibose in 35 ml of dry 1,2-dichloroethane was added 2.08 g (0.0046 mol) of tris-trimethylsilyl-5-iodocytosine followed by 1.11 g (0.005 mol) of trifluoromethanesulfonyloxytrimethylsilane. The reaction mixture was refluxed for about 16 hours under a nitrogen atmosphere and cooled to room temperature. Five milliliters of methanol were added to the reaction mixture and the mixture was stirred for an additional 30 minutes. The mixture was filtered and the precipitated solid was collected by filtration. The filtrate was evaporated to dryness under reduced pressure, and the resulting residue was dissolved in 20 ml of dichloromethane saturated with anhydrous hydrogen bromide. This mixture was stirred for about 3 hours. The volatiles were removed in vacuo at 45° C. The residue was dissolved in 15 ml of water, neutralized to pH 7-8 with 10% sodium bicarbonate, and the resulting solution was washed once with 10 ml of ethyl acetate. The aqueous layer was chromatographed on a Whatman Prep ODS-3 reverse phase column in 2.0 ml portions using water/methanol (9:1, v:v) to afford 30 mg of 1-(4-amino-5-iodo-2-oxo-1H-pyrimidin-1-yl)-2-desoxy-2,2-difluororibose.

Workup

  1. temperatureThe reaction mixture was refluxed for about 16 hours under a nitrogen atmosphere
  2. filtrationThe mixture was filtered
  3. filtrationthe precipitated solid was collected by filtration
  4. customThe filtrate was evaporated to dryness under reduced pressure
  5. dissolutionthe resulting residue was dissolved in 20 ml of dichloromethane saturated with anhydrous hydrogen bromide
  6. stirringThis mixture was stirred for about 3 hours
  7. customThe volatiles were removed in vacuo at 45° C
  8. dissolutionThe residue was dissolved in 15 ml of water
  9. washthe resulting solution was washed once with 10 ml of ethyl acetate
  10. customThe aqueous layer was chromatographed on a Whatman Prep ODS-3 reverse phase column in 2.0 ml portions

Sources & evidence

ORD record
ord-89d819365bae475599e9f275cc45820f
Source dataset
uspto-grants-1995_11
Patent number
US05464826

Reaction notes

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