Gemcitabine → HCID 49768039, 화합물

HRID 1157352

반응식

HRID 1157352 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

반응물 3

HCID 60750GemcitabineHCID 65578Oxalyl chlorideHCID 802471,2-Ethylenediphosphonic Acid

생성물 1

HCID 49768039HCID 49768039, 화합물수율 3.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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, 5 mL) and stirred for 30 minutes. Purification by HPLC gave 7.8 mg of the titled compound 81.

후처리

  1. temperatureAfter heating
  2. temperatureat reflux for 10 minutes under argon
  3. customa solution was obtained and after a further 3 h the reaction mixture
  4. customevacuated in vacuo
  5. dissolutionThe residue was dissolved in anhydrous trimethyl phosphate (2 mL)
  6. temperaturecooled to −15° C.
  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-878d714863ef449a92d58a60a3ff4825
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807653B2

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