| 摘要 |
The present invention relates to an improved as well as an industrially viable process for the preparation of 2'-deoxy-2',2'-difluorocytidine and its pharmaceutical acceptable acid salts thereof in high purity and acceptable yield by using a simple and inexpensive process. The process involves reacting an alpha anomer enriched 2'-deoxy-2',2'-difluorocarbohydrate with silylated nucleobase derivatives via the SN2 displacement of an anomeric sulfonyloxy group in an inert solvent to produce 2',2'-difluoro-2'-deoxycytidine-3',5'-dibenzoate in about a 5:1 β/α anomeric ratio, and a process for selectively isolating β-2',2'-difluoro-2'-deoxycytidine-3',5'- dibenzoate from the 5:1 β/α anomeric mixture. The pure β-2',2'-difluoro-2'- deoxycytidine-3',5'-dibenzoate is then converted to the corresponding nucleoside utilizing ammonium hydroxide in a polar and preferably protic solvent to obtain β- 2'-deoxy-2',2'-difluorocytidine, which is thereafter converted to gemcitabine hydrochloride that is effective against non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. The present invention relates to an improved and convenient method for preparing antineoplastic nucleosides, more particularly, a process for preparing gemcitabine hydrochloride, represented by the formula I below, which exhibits good antitumor activity. (I) |
