Deoxyuridine → Edoxudin

HRID 973796Notes

Reaction equation

HRID 973796 reaction equation
[C@@H:1]1([N:9]2[CH:16]=[CH:15][C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.Cl[C@@H:18]1[C@@H](CO)O[C@@H](N2C=CC(=O)NC2=O)[CH2:19]1.[N-]=[N+]=[N-].[Li+]>CN(P(N(C)C)(N(C)C)=O)C>[CH2:18]([C:15]1[C:13](=[O:14])[NH:12][C:10](=[O:11])[N:9]([CH:16]=1)[C@@H:1]1[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1)[CH3:19]

Participants

5

Reactant 3

HCID 13712DeoxyuridineHCID 88163Lithium azideHCID 566191273'-Chloro-2',3'-dideoxyuridine

Product 1

HCID 66377Edoxudin

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent

Procedure

5-Chloromercuri-2'-deoxyuridine was prepared from 2'-deoxyuridine (10 g, 0.044 moles) by the procedure of Bergstron and Ruth (J. Carb. Nucl, and Nucl., 4,257, (1977)). 2'-Deoxy-5-ethyluridine was prepared by the method of Berstrom et al., (J. Am. Chem. Soc., 100, 8106, (1978)). The 5'-hydroxyl group was protected by the method of Example 62. The 3'-hydroxyl group was chlorinated and the 5'-hydroxyl was deprotected by the method of Example 64. The 3'-chloro of threo 3'-chloro-2',3'-dideoxyuridine was displaced with inversion of configuration by heating in HMPA with lithium azide (5 eq.) at 55° C. for one hour. The title compound was purified by chromatography on silica gel eluted with ethyl acetate. Removal of solvent from the appropriate fractions gave the desired compound; mp=112.5°-115° C.

Workup

  1. customThe title compound was purified by chromatography on silica gel
  2. washeluted with ethyl acetate
  3. customRemoval of solvent from the appropriate fractions

Sources & evidence

ORD record
ord-b9ebce20dad547bcbf06f3f4ae325a6b
Source dataset
uspto-grants-1991_11
Patent number
US05064946

Reaction notes

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