Method for preparing gemcitabine hydrochloride and intermediate thereof with high selectivity

A gemcitabine hydrochloride, high selectivity technology, applied in the field of highly selective preparation of gemcitabine hydrochloride and its intermediates

Inactive Publication Date: 2011-08-17
湖南欧亚药业有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0015] Although the method has good stereo configuration selectivity of the product, it uses a highly irritating fuming liquid trifluoroacetic acid in the ring-closing reaction, and the operation is complicated. It is not conducive to industrialization; at the same time, the reduction reaction uses lithium aluminum hydride as a reducing agent, which is very dangerous for industrial production

Method used

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  • Method for preparing gemcitabine hydrochloride and intermediate thereof with high selectivity
  • Method for preparing gemcitabine hydrochloride and intermediate thereof with high selectivity
  • Method for preparing gemcitabine hydrochloride and intermediate thereof with high selectivity

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Experimental program
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Embodiment Construction

[0054] A highly selective method for preparing gemcitabine hydrochloride and its intermediates, the process is:

[0055]

[0056] 2 3 4

[0057]

[0058] 5 6 7

[0059]

[0060]

[0061] 10 1

[0062] Wherein the synthesis of compound (3):

[0063] Add 250 milliliters of tetrahydrofuran, 130 grams of zinc powder (1.98mol), and 5.1 milliliters of dibromoethane into the reaction flask, stir, heat up to 40°C, add 7.6 milliliters of trimethylchlorosilane, continue stirring at this temperature for 30 minutes, and then Raise to 60°C, slowly add dropwise 400 ml of tetrahydrofuran solution dissolved with 308 g of D-glyceraldehyde acetonide (compound 2) (2.36 mol) and 255 ml (1.98 mol) of ethyl bromodifluoroacetate, and heat up to reflux for reaction 2 hours, then cooled to room temperature; the reaction solution was poured into a mixed solution of 3000 grams of ice, 800 milliliters of ether and 2500 milliliters of 1M hydrochloric acid, and stirred for 30 minutes. ...

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Abstract

The invention discloses a method for synthesizing an important intermediate 2-deoxy-2, 2-difluorofuran ribose compound of gemcitabine hydrochloride and a method for synthesizing the gemcitabine hydrochloride by using the compound as a raw material under the catalysis of cytosine. The method has good stereo selectivity, a mild reaction condition, easily obtained raw materials, low pollution and high yield, and is suitable for industrialized production.

Description

technical field [0001] The invention relates to a novel and highly selective synthetic method for preparing gemcitabine hydrochloride and its important intermediate 2-deoxy-2,2-difluororibofuranose compound. Background technique [0002] Gemcitabine Hydrochloride (Gemcitabine Hydrochloride), chemically named 2'-deoxy-2,2-difluorocytidine hydrochloride (β isomer), is a pyrimidine nucleoside analog developed by Eli Lilly and Company of the United States. It was released in Australia in 1995 , Finland and other countries listed, the product name is Gemzar. my country has now approved the import, and the Chinese product name is Jianze. Its structure is similar to Cytarabine, which belongs to nucleoside anti-metabolism and anti-tumor drugs, and is suitable for non-small cell carcinoma, pancreatic cancer, bladder cancer, breast cancer and other solid tumors. [0003] The preparation route of gemcitabine hydrochloride mainly contains following several kinds: [0004] Route 1 [He...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H5/02C07H19/06C07H1/00
Inventor 林开朝
Owner 湖南欧亚药业有限公司
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