Gemcitabine → HCID 49768039、化合物

HRID 1157352

反応式

HRID 1157352 の反応式
[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][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]

参加物

5

反応物 3

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

生成物 1

HCID 49768039HCID 49768039、化合物収率 3.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-878d714863ef449a92d58a60a3ff4825
出典データセット
uspto-grants-2010_10
特許番号
US07807653B2

関連ノート

読み込み中…