Method for removing protective groups and preparing dimethoxy taxane compound

A technology for dimethoxytaxane and deprotection group, which is applied in the field of preparation of dimethoxytaxane compounds by deprotection group, can solve the problems of reducing reaction yield and product purity, and achieve improvement of reaction yield and product purity, simple operation, and easy industrial production

Inactive Publication Date: 2012-04-25
JIANGSU HONGDOUSHAN BIOLOGICAL TECH
View PDF2 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Patent CN 1179776A discloses a preparation method of this compound, that is, through 3-tert-butoxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1 under acidic conditions , 3-oxazolidine-5-carboxylic acid 4α-acetoxy-2α-ben

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 removing protective groups and preparing dimethoxy taxane compound
  • Method for removing protective groups and preparing dimethoxy taxane compound
  • Method for removing protective groups and preparing dimethoxy taxane compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Dissolve p-toluenesulfonic acid (5.0 g, 26.3 mmol) in 500 mL of methanol, add 100.0 g of 200-300 mesh silica gel, stir well at room temperature for 1 hour, and rotary evaporate to dryness to obtain acid-activated silica gel.

[0019] Dissolve 12.00 g of the prepared acid-activated silica gel in 500 mL of methanol, add compound (1) (10.00 g, 10.5 mmol), and react at room temperature for 1 hour. TLC shows that the reaction is complete. The reaction solution was filtered with suction, and the filtrate was concentrated to dryness to obtain a crude product of dimethoxytaxane compound (2), which was obtained through 200-300 mesh silica gel column chromatography (petroleum ether: ethyl acetate = 1: 1) to obtain dimethoxytaxane compound (2). Methoxytaxane compound (2) (8.58g, 10.3mmol), yield 97.8%, purity 95.6%.

Embodiment 2

[0021] Dissolve camphorsulfonic acid (6.1 g, 26.3 mmol) in 500 mL of methanol, add 100.0 g of 200-300 mesh silica gel, stir well at room temperature for 1 hour, and rotary evaporate to dryness to obtain acid-activated silica gel.

[0022] Dissolve 12.00 g of the prepared acid-activated silica gel in 500 mL of methanol, add compound (1) (20.00 g, 21.0 mmol), and react at room temperature for 1 hour. TLC shows that the reaction is complete. The reaction solution was filtered with suction, and the filtrate was concentrated to dryness to obtain a crude product of dimethoxytaxane compound (2), which was obtained through 200-300 mesh silica gel column chromatography (petroleum ether: ethyl acetate = 1: 1) to obtain dimethoxytaxane compound (2). Methoxytaxane compound (2) (17.1 g, 20.5 mmol), yield 97.5%, purity 96.5%.

Embodiment 3

[0024] Dissolve concentrated sulfuric acid (2.6 g, 26.3 mmol) in 500 mL of methanol, add 100.0 g of 200-300 mesh silica gel, stir well at room temperature for 1 hour, and rotary evaporate to dryness to obtain acid-activated silica gel.

[0025] Dissolve 12.00 g of the prepared acid-activated silica gel in 500 mL of methanol, add compound (1) (10.00 g, 10.5 mmol), and react at room temperature for 1 hour. TLC shows that the reaction is complete. The reaction solution was filtered with suction, and the filtrate was concentrated to dryness to obtain a crude product of dimethoxytaxane compound (2), which was obtained through 200-300 mesh silica gel column chromatography (petroleum ether: ethyl acetate = 1: 1) to obtain dimethoxytaxane compound (2). Methoxytaxane compound (2) (8.58g, 10.3mmol), yield 97.7%, purity 95.8%.

[0026] The resulting product is subjected to nuclear magnetic resonance testing.

[0027] NMR spectrum such as figure 1 Shown: 1 H-NMR (400MHz: CDCl 3 ; chem...

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 removing protective groups and preparing a dimethoxy taxane compound. The invention belongs to the technical field of medicines used for treating prostate cancer. According to the invention, an acid is dissolved in methanol; silica gel with a specification of 100-800 meshes is added to the solution, and the solution is sufficiently stirred under room temperature; the solution is dried by rotary evaporation, such that acid-activated silica gel is obtained; the acid-activated silica gel is dissolved in an organic solvent; a compound 3-Boc-2-p-methoxy phenyl-4-phenyl-(2R,4S,5R)-1,3-oxazolidine-5-carboxylate 4alpha-acetoxy-2alpha-benzoyloxy-5beta,20-epoxy-1beta-hydroxyl-9-oxygen-7beta,10beta-dimethoxy-11-taxadiene-13alpha ester is added to the solution; the mixture is continuously stirred, and is subject to a reaction; an obtained reaction liquid is processed through pump filtration; an obtained filtrate is dried by condensation, and is processed through silica gel column chromatography, such that the product dimethoxy taxane compound is obtained. According to the invention, the protective groups are removed in an acidic environment, such that the dimethoxy taxane compound is prepared. The method is advantaged in simple operation, suitability for industrialized productions, no by-product during the reaction process, improved reaction yield, and improved product purity.

Description

technical field [0001] The present invention relates to a method for preparing dimethoxytaxane compounds through deprotection, in particular to a method for preparing dimethoxytaxanes through 3-tert-butoxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S,5R)-1,3-oxazolidine-5-carboxylic acid 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-9-oxo-7β,10β- Deprotection of dimethoxy-11-taxene-13α ester to prepare 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,10β-dimethoxy The method of -9-oxotaxane-11-ene-13α-yl-(2R,3S)-3-tert-butoxycarbonylamino-2-hydroxyl-3-phenylpropionate belongs to the drug for treating prostate cancer technology field. Background technique [0002] 4α-acetoxy-2α-benzoyloxy-5β, 20-epoxy-1β-hydroxy-7β, 10β-dimethoxy-9-oxotaxane-11-en-13α-yl- (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate (2) is an effective drug for the treatment of advanced prostate cancer. Patent CN 1179776A discloses a preparation method of this compound, that is, throu...

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): C07D305/14
CPCY02P20/55
Inventor 陈磊郑伟李隆王琼徐信保
Owner JIANGSU HONGDOUSHAN BIOLOGICAL TECH
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