Method for semisynthesis of Docetaxel and intermediate of Docetaxel

A technology for docetaxel and intermediates, applied in the field of pharmaceutical chemical synthesis, can solve the problems of 10-DABⅢ raw material waste, easy reaction to generate other impurities, and loss of docetaxel products, so as to achieve less impurity generation and simple and easy operation Effect of control and less by-products

Inactive Publication Date: 2017-09-08
CHONGQING BEISHENG PHARMA TECH CO LTD
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The common problem in the semi-synthetic method of docetaxel in the prior art is: using 10-DABⅢ as a raw material, the final yield of docetaxel is low
The main reasons for this problem are as follows: (1) in the process of carrying out hydroxyl protection to 10-DABⅢ 7-position hydroxyl and 10-position hydroxyl, it is easy to form simultaneous protection of 7-position hydroxyl, 10-position hydroxyl...

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for semisynthesis of Docetaxel and intermediate of Docetaxel
  • Method for semisynthesis of Docetaxel and intermediate of Docetaxel
  • Method for semisynthesis of Docetaxel and intermediate of Docetaxel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] (1) Weigh the raw material of 10-DABⅢ, add dry pyridine and stir to dissolve, then add 2,2,2-trichloroethyl chloroformate dropwise under the protection of nitrogen, the dropping time is kept at 20min, and the dropping temperature is controlled at 0 ℃, after the dropwise addition is completed, control the reaction temperature to 10°C, stop the reaction when the 7-hydroxyl protected by-product of 10-DABⅢ in the reaction solution is 5%, quench the reaction by adding water dropwise, and then neutralize pyridine with concentrated hydrochloric acid , extracted with dichloromethane, concentrated and dried to obtain the crude intermediate Ⅰ.

[0044] Among them, the mass ratio of 10-DABⅢ raw material, dry pyridine, and 2,2,2-trichloroethyl chloroformate is 1:3:0.6.

[0045] (2) Weigh the crude product of intermediate I, dissolve it with an organic solvent, filter, and then separate and collect the eluate containing intermediate I and the 7-position hydroxyl protection by-produc...

Embodiment 2

[0057] (1) Weigh the 10-DABⅢ raw material, add dry pyridine and stir to dissolve, then add 2,2,2-trichloroethyl chloroformate dropwise under the protection of nitrogen, the dropping time is kept at 40min, and the dropping temperature is controlled at 10 ℃, after the dropwise addition is completed, control the reaction temperature to 35°C, stop the reaction when the 7-hydroxyl protected by-product of 10-DABⅢ in the reaction liquid is 10%, add water dropwise to quench the reaction, and then neutralize pyridine with concentrated hydrochloric acid , extracted with dichloromethane, concentrated and dried to obtain the crude intermediate Ⅰ.

[0058] Among them, the mass ratio of 10-DABⅢ raw material, dry pyridine, and 2,2,2-trichloroethyl chloroformate is 1:8:2.

[0059] (2) Weigh the crude product of intermediate I, dissolve it in an organic solvent, filter it, and then separate and collect the eluent containing intermediate I and the 7-position hydroxyl protection by-product throu...

Embodiment 3

[0071] (1) Weigh the 10-DABⅢ raw material, add dry pyridine and stir to dissolve, then add 2,2,2-trichloroethyl chloroformate dropwise under the protection of nitrogen, the dropping time is kept at 30min, and the dropping temperature is controlled at 5 ℃, after the dropwise addition is completed, control the reaction temperature to 20°C, stop the reaction when the 7-position hydroxyl protection by-product of 10-DABⅢ in the reaction solution is 8%, quench the reaction by adding water dropwise, and then neutralize the pyridine with concentrated hydrochloric acid , extracted with dichloromethane, concentrated and dried to obtain the crude intermediate Ⅰ.

[0072] Among them, the mass ratio of 10-DABⅢ raw material, dry pyridine, and 2,2,2-trichloroethyl chloroformate is 1:5:1.3.

[0073] (2) Weigh the crude product of intermediate I, dissolve it with an organic solvent, filter, and then separate and collect the eluate containing intermediate I and the 7-position hydroxyl protectio...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a method for semisynthesis of Docetaxel and an intermediate of the Docetaxel. The method provided by the invention comprises the steps of firstly, carrying out hydroxyl protection on C7 and C10 of 10-DAB III (10-deacetylbaccatin III) by using 2,2,2-trichloroethylchloroformate so as to obtain an intermediate I, subjecting the intermediate I to a reaction with a side chain radical compound so as to prepare an intermediate II, subjecting the intermediate II to a hydrogenation reaction under the catalysis of palladium-charcoal so as to prepare an intermediate III, subjecting the intermediate III to a reaction under acidic conditions so as to obtain a Docetaxel crude product, and subjecting the Docetaxel crude product to purification, thereby obtaining a purified product. According to the method provided by the invention, the 10-DAB III raw material can be sufficiently utilized, finally-produced byproducts are few, the final product Docetaxel has the purity of 99.6% to 99.9%, the mole yield reaches up to 73% to 82%, and the utilization ratio of the 10-DAB III can be greatly increased.

Description

technical field [0001] The invention belongs to the field of pharmaceutical chemical synthesis, and in particular relates to a method for semi-synthesizing docetaxel and an intermediate thereof. Background technique [0002] Docetaxel (trade name Taxotere) is a taxane diterpenoid compound that is chemically synthesized or semi-synthesized. [0003] The mechanism of action of docetaxel is to enhance tubulin polymerization and inhibit microtubule depolymerization, leading to the formation of stable non-functional microtubule bundles, thereby disrupting the mitosis of tumor cells. The intracellular concentration of docetaxel is 3 times higher than that of paclitaxel, and the intracellular residence time is longer, which is an important reason why docetaxel has greater antitumor activity than paclitaxel in vitro. In the in vivo test, it is effective against colon cancer, breast cancer, lung cancer, and ovarian tumor transplantation in mice. [0004] However, in the prior art, ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D305/14C07D413/12
CPCC07D305/14C07D413/12
Inventor 潘敬坤张龙
Owner CHONGQING BEISHENG PHARMA TECH CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap