Gemcitabine → 2'-Deoxy-2',2'-difluorocytidine 5'-ethylenediphosphonate
반응식
[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][C:18]1([F:34])[C@H:22]([OH:23])[C@@H:21]([CH2:24]O)[O:20][C@H:19]1[N:26]1[CH:33]=[CH:32][C:30]([NH2:31])=[N:29][C:27]1=[O:28]>CN(C=O)C>[CH2:1]([P:7]([O:9][CH2:24][C@H:21]1[O:20][C@@H:19]([N:26]2[CH:33]=[CH:32][C:30]([NH2:31])=[N:29][C:27]2=[O:28])[C:18]([F:17])([F:34])[C@@H:22]1[OH:23])(=[O:8])[OH:10])[CH2:2][P:3](=[O:5])([OH:4])[OH:6]참가 물질
5
실험 절차
Ethylenediphosphonic acid (173 mg, 0.91 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 argon, a solution was obtained and after a further 3 h the reaction mixture was cooled to room temperature and evacuated in vacuo. The residue was co-evaporated with anhydrous acetonitrile (3×10 ml). The residue was dissolved in anhydrous trimethyl phosphate (2 mL), cooled to −15° C. and 2′deoxy-2′,2′-difluorocytidine (93 mg, 0.46 mmol) was added under argon. After stirring for 2 h the reaction mixture was quenched with ice-cold TEAB solution (1.0 M, mL) and stirred for 30 minutes. Purification by HPLC gave 7.8 mg of the titled compound 81.
후처리
- temperatureAfter heating
- temperatureat reflux for 10 minutes under argon
- customa solution was obtained and after a further 3 h the reaction mixture
- customevacuated in vacuo
- dissolutionThe residue was dissolved in anhydrous trimethyl phosphate (2 mL)
- temperaturecooled to −15° C.
- customwas quenched with ice-cold TEAB solution (1.0 M, mL)
- stirringstirred for 30 minutes
- customPurification by HPLC
출처 및 근거
- ORD 기록
- ord-530120d932fc483daabf42c48e4f606d
- 출처 데이터셋
- uspto-grants-2009_10
- 특허 번호
- US07598230B2
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