Oxalyl chloride → (E)-2'-Deoxy-2'-(fluoromethylene)cytidine 5'-ethylenediphosphonate

HRID 1157351

반응식

HRID 1157351 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]/[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]

참가 물질

5

반응물 3

HCID 65578Oxalyl chlorideHCID 802471,2-Ethylenediphosphonic AcidHCID 6435808Tezacitabine

생성물 1

HCID 86591514(E)-2'-Deoxy-2'-(fluoromethylene)cytidine 5'-ethylenediphosphonate수율 2.7%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-1d773c1d2be2451486d5fe319b1e20ef
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807653B2

연결된 노트

불러오는 중…