草酰氯 → HCID 86591514，化合物

HRID 1817519

反应方程式

HRID 1817519 反应方程式
[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]

参与物

5

反应物 3

HCID 65578草酰氯HCID 802471,2-乙烯基二膦酸HCID 6435808(E)-2'-DEOXY-2'-(FLUOROMETHYLENE) CYTIDINE

产物 1

HCID 86591514HCID 86591514，化合物收率 2.7%

试剂、催化剂与溶剂 1

HCID 6228N,N-二甲基甲酰胺溶剂

实验过程

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.

后处理

  1. temperatureAfter heating
  2. temperatureat reflux for 10 minutes under an argon atmosphere a solution
  3. customwas obtained and after a further 3 h the reaction mixture
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in anhydrous trimethyl phosphate (2 mL)
  6. temperaturecooled to −15° C. under an argon
  7. customwas quenched with ice-cold TEAB solution (1.0 M, 5 mL)
  8. stirringstirred for 30 minutes
  9. customPurification by HPLC

来源与证据

ORD记录
ord-e63d22421dba419bae66ae2218880be5
来源数据集
uspto-grants-2009_10
专利号
US07598230B2

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