Synthesis method of taxane drug 7, 10-methoxy-docetaxel

A synthetic method and taxane technology, applied in organic chemistry, bulk chemical production, etc.

Active Publication Date: 2012-11-21
无锡紫杉药业股份有限公司
View PDF8 Cites 13 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Although the above-mentioned preparation method has fewer steps, it has the disadvantages of using strong low-temperature refrigeration equipment and highly toxic methylating reagents such as methyl iodide or dimethyl sulfate, In view of this, the present invention is proposed, which relates to a synthetic method that can prepare 7,10-methoxy docetaxel under mild conditions without using highly toxic methyl iodide and strong low-temperature cooling equipment

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
  • Synthesis method of taxane drug 7, 10-methoxy-docetaxel
  • Synthesis method of taxane drug 7, 10-methoxy-docetaxel
  • Synthesis method of taxane drug 7, 10-methoxy-docetaxel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Embodiment 1 (R is a triethylsilyl protecting group, TES-)

[0053] Step 1: 7,10-Hydroxy-13-triethylsilyloxy-10-desacetylbaccatin III (compound 2 ) preparation

[0054] 7,10-trichloroethoxycarbonyl-10-desacetylbaccatin III (compound 1 ) (50 g, 55.9 mmol) was fully dissolved in DMF (500 mL), then 2-methylimidazole (6.9 g, 83.8 mmol) was added, and triethylchlorosilane (11.3 mL, 67.0 mmol) was added dropwise and the reaction was stirred at room temperature After 12 hours, 2000 mL of water was added to the reaction solution, extracted with ethyl acetate (300 mL×3), the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered with suction. Add zinc powder (4.4 g, 67.0 mmol), methanol (18 mL), acetic acid (3.8 mL, 67.0 mmol) to the filtrate, stir at room temperature and react for 12 hours, filter with suction, concentrate, add 500 mL of acetonitrile to the reaction solution, and react A large amount of solids precipitated out in t...

Embodiment 2

[0065] Example 2 (R is a tert-butyldimethylsilyl protecting group, TBS-)

[0066] Step 1: 7,10-hydroxy-13-tert-butyldimethylsilyloxy-10-deacetylbaccatin III (compound 2 ) preparation

[0067] 7,10-trichloroethoxycarbonyl-10-desacetylbaccatin III (compound 1 ) (50 g, 55.9 mmol) was fully dissolved in DMF (500 mL), 2-methylimidazole (6.9 g, 83.8 mmol) was added, and tert-butyldimethylsilyl chloride (11.3 mL, 67.0 mmol) was added dropwise After stirring and reacting at room temperature for 12 hours, 2000 mL of water was added to the reaction liquid, extracted with ethyl acetate (300 mL×3), the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered with suction. Add zinc powder (4.4 g, 67.0 mmol), methanol (18 mL), acetic acid (3.8 mL, 67.0 mmol) to the filtrate, stir at room temperature and react for 12 hours, filter with suction, concentrate, add 500 mL of acetonitrile to the reaction solution, and react A large amount of solids pre...

Embodiment 3

[0078] Embodiment 3 (R is triethylsilyl protecting group, TES-)

[0079] Step 1: 7,10-Hydroxy-13-triethylsilyloxy-10-desacetylbaccatin III (compound 2 ) preparation

[0080] 7,10-trichloroethoxycarbonyl-10-desacetylbaccatin III (compound 1 ) (50 g, 55.9 mmol) was fully dissolved in DMF (500 mL), then 2-methylimidazole (4.6 g, 55.9 mmol) was added, and triethylchlorosilane (9.4 mL, 55.9 mmol) was added dropwise and the reaction was stirred at room temperature After 12 hours, 2000 mL of water was added to the reaction solution, extracted with ethyl acetate (300 mL×3), the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered with suction. Add zinc powder (3.7 g, 55.9 mmol), methanol (18 mL), acetic acid (3.2 mL, 55.9 mmol) to the filtrate, stir and react at 20°C for 12 hours, filter with suction, concentrate, add 500 mL of acetonitrile to the reaction liquid, A large amount of solids were precipitated in the reaction solution, suct...

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 discloses a synthesis method of taxane drug 7, 10-methoxy-docetaxel. The synthesis method includes using 7, 10-trichloro-ethoxycarbonyl-10-deacetylbaccatin III (compound 1, CAS (chemical abstracts service) number 95603-44-4) as starting material, using triethyl silicon substrate for protection, and performing reactions of removal of protecting group of trichloro-ethoxycarbonyl, dimethyl sulfide etherification, hydrogenation reduction, removal of protecting group of the triethyl silicon substrate, side chain condensation and side chain deprotection to obtain the 7, 10-methoxy-docetaxelf with more than 99% purity. Reaction conditions are simple and mild. The synthesis method has the advantages that the required equipment is simple and is easy to operate, and methylate reagents such as highly toxic methyl iodide or dimethyl sulfate is not needed. The synthesis method is applicable to industrial production.

Description

technical field [0001] The invention relates to a method for synthesizing 7,10-methoxy docetaxel, which is a medicine for treating prostate cancer, and belongs to the field of medicine synthesis. Background technique [0002] 7,10-Methoxydocetaxel was developed by Sanofi-Aventis in France and was approved by the US Food and Drug Administration (FDA) on June 17, 2010. The drug is an injection and is mainly used to treat advanced, hormone-refractory prostate cancer that has progressed during or after docetaxel treatment. [0003] [0004] Structural Formula 1 Structure of 7,10-methoxydocetaxel. [0005] Prostate cancer is the most common malignant tumor of the male reproductive system, and its incidence increases with age. There are obvious regional differences in its incidence, and the incidence is higher in Europe and America. It is reported that after lung cancer, it is the second leading cause of cancer death in men. The incidence rate in my country was low before, b...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/14
CPCY02P20/55
Inventor 陈磊赵洪涛黄春王琼喻琼林
Owner 无锡紫杉药业股份有限公司
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