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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
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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-benzoyloxy-5β, 20-epoxy-1β-hydroxy-9-oxo-7β, 10β-dimethoxy-11 -Taxene-13α ester (1) removes protecting group, but this preparation method can cause the generation of by-product, thereby reduces reaction yield and product purity

Method used

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  • 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...

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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

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Application Information

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IPC IPC(8): C07D305/14
CPCY02P20/55
Inventor 陈磊郑伟李隆王琼徐信保
Owner JIANGSU HONGDOUSHAN BIOLOGICAL TECH
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