Reaction equation
[CH2:1]([P:7](=[O:10])([OH:9])[OH:8])[CH2:2][P:3](=[O:6])([OH:5])[OH:4].C(Cl)(=O)C(Cl)=O.[F:17]/[CH:18]=[C:19]1/[C@H:20]([N:27]2[CH:34]=[CH:33][C:31]([NH2:32])=[N:30][C:28]2=[O:29])[O:21][C@H:22]([CH2:25]O)[C@H:23]/1[OH:24]>CN(C=O)C>[CH2:1]([P:7]([O:9][CH2:25][C@H:22]1[O:21][C@@H:20]([N:27]2[CH:34]=[CH:33][C:31]([NH2:32])=[N:30][C:28]2=[O:29])/[C:19](=[CH:18]/[F:17])/[C@@H:23]1[OH:24])(=[O:8])[OH:10])[CH2:2][P:3](=[O:5])([OH:4])[OH:6]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
Ethylenediphosphonic acid (100 mg, 0.53 mmol) was treated with oxalyl chloride (2 mL, as solvent) and anhydrous DMF (0.1 mL, cat.). After heating at reflux for 10 minutes under an argon atmosphere a solution was obtained and after a further 3 h the reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was coevaporated with anhydrous acetonitrile (3×10 mL). The residue was dissolved in anhydrous trimethyl phosphate (2 mL), cooled to −15° C. under an argon and (E)-2′-deoxy-2′-(fluoromethylene)cytidine (64 mg, 0.25 mmol) was added. After stirring for 2 h the reaction mixture was quenched with ice-cold TEAB solution (1.0 M, 5 mL) and stirred for 30 minutes. Purification by HPLC gave 2.9 mg of the titled compound 80.
Workup
- temperatureAfter heating
- temperatureat reflux for 10 minutes under an argon atmosphere a solution
- customwas obtained and after a further 3 h the reaction mixture
- concentrationconcentrated in vacuo
- dissolutionThe residue was dissolved in anhydrous trimethyl phosphate (2 mL)
- temperaturecooled to −15° C. under an argon
- customwas quenched with ice-cold TEAB solution (1.0 M, 5 mL)
- stirringstirred for 30 minutes
- customPurification by HPLC
Sources & evidence
- ORD record
- ord-a9df77ca5abb41ae9d32b10c737f062d
- Source dataset
- uspto-grants-2007_10
- Patent number
- US07285658B2
Linked notes
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