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Method for preparing cabazitaxel by taking 10-deacetylate-baccatin III as raw material

A technology for deacetylation and cabazitaxel, which is applied in the field of drug synthesis, can solve problems such as long synthesis paths, and achieve the effects of saving labor, simplifying operation steps, and increasing preparation and metering.

Active Publication Date: 2012-04-18
无锡紫杉药业股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The synthetic route is relatively long, and six-step reactions are required to obtain cabazitaxel in the final synthesis
And the synthesis process described in the patent is small amount (50mg level)

Method used

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  • Method for preparing cabazitaxel by taking 10-deacetylate-baccatin III as raw material
  • Method for preparing cabazitaxel by taking 10-deacetylate-baccatin III as raw material
  • Method for preparing cabazitaxel by taking 10-deacetylate-baccatin III as raw material

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] (1) Suspend 10.0g (0.018mol) of 10-DAB in 250mL of chloroform in a 500mL reaction flask, add 5mL of pyridine under mechanical stirring, and control the temperature to 0°C with an ice-salt bath. Then, a solution of 5.46 mL (0.040 mol) of trichloroethyl chloroformate in 20 mL of chloroform was added dropwise into the reaction flask. The dropwise addition is completed in about 1 hour, and the rate of addition is controlled so that the temperature of the reaction solution in the reaction bottle is below 5 degrees Celsius. After stirring for another hour, the ice-salt bath was removed; according to the detection of TLC, after the reaction of 10-DAB was completed, 100 mL of 0.5 mol / L hydrochloric acid was added dropwise with the ice-salt bath turned on, and the lower aqueous phase was separated by standing, and then added 100mL of 0.5mol / L hydrochloric acid solution was stirred and the lower aqueous phase was separated. Then, after washing with 50 mL of saturated brine, the ...

Embodiment 2

[0032] (1) Suspend 100.0 g (0.18 mol) of 10-DAB in 2.5 L of dichloromethane in a 500 mL reaction flask, and add 50 mL of pyridine in ice-salt water bath to 0 degrees Celsius under the condition of mechanical stirring. Then, a solution of 54.6 mL (0.40 mol) of trichloroethyl chloroformate in 200 mL of dichloromethane was added dropwise into the reaction flask. The dropwise addition is completed in about 1 hour, and the rate of addition is controlled so that the temperature of the reaction solution in the reaction bottle is below 5 degrees Celsius. After stirring for another 1 hour, the ice-salt bath was removed; after the 10-DAB reaction was completed according to the detection of TLC, 1000 mL of 0.5 mol / L hydrochloric acid was added dropwise under the condition of opening the ice bath, and the lower aqueous phase was separated, and then 1000 mL was added. .5mol / L hydrochloric acid solution was stirred and the lower aqueous phase was separated. Then, after washing with 500 mL ...

Embodiment 3

[0039] (1) Suspend 200.0 g (0.36 mol) of 10-DAB in 6 L of chloroform in a 10 L reaction flask, and add 100 mL of pyridine to ice-salt water bath to 0 degrees Celsius under the condition of mechanical stirring. Then, a solution of 109.2 mL (0.80 mol) of trichloroethyl chloroformate in 400 mL of dichloromethane was added dropwise into the reaction flask. The dropwise addition is completed in about 1 hour, and the rate of addition is controlled so that the temperature of the reaction solution in the reaction bottle is below 5 degrees Celsius. After stirring for another 1 hour, the ice-salt bath was removed; after the 10-DAB reaction was completed according to the detection of TLC, 2000 mL of 0.5 mol / L hydrochloric acid was added dropwise with the ice bath turned on, and the lower aqueous phase was separated, and then 2000 mL was added. .5mol / L hydrochloric acid solution was stirred and the lower aqueous phase was separated. Then, after washing with 1000 mL of saturated brine, th...

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Abstract

The invention relates to a method for preparing cabazitaxel, particularly relates to a method for preparing the cabazitaxel by taking 10-deacetylate-baccatin III as a raw material and belongs to the technical field of drug synthesis. The method comprises the following steps: firstly, reacting 10-DAB with chlorocarbonate-2,2,2-trichloro ethyl ester, thereby obtaining a product; reacting the product with DMAP (dimethylamino pyridine), DCC (dicyclohexylcarbodiimide) and (4S, 5R)-2,2-dimethyl-4-phenyl-3-tert-butoxycarbonyl-3.5-oxazolidine formic acid, thereby obtaining a product; reacting the product with acetic acid and zinc powder, and then methylating the product; and lastly, adding a p-methyl benzenesulfonic acid, thereby reacting and obtaining a cabazitaxel product. The cabazitaxel prepared according to the method can be widely applied to the treatment of prostate cancer. Compared with a traditional technique for preparing the cabazitaxel, the method has the advantages that the preparation quantity is greatly increased, the operation steps are simplified, the manpower is saved and the method has industrial application value and prospect.

Description

technical field [0001] The invention relates to a method for preparing cabazitaxel, in particular to a method for preparing cabazitaxel by using 10-deacetyl-baccatin III as a raw material, and belongs to the technical field of drug synthesis. Background technique [0002] In June 2010, the anti-prostate cancer drug cabazitaxel (JEVTANA), namely 7,10-dimethylated docetaxel (CAS#: 183133-96-2; Chemical Formula: C 45 h 57 NO 14 ) has a simplified structure as follows: [0003] [0004] Prostate cancer has a high incidence rate in Europe and the United States, but relatively low incidence rate in Asia. Studies have shown that the disease is closely related to living habits and diet structure. For example, the incidence rate of prostate cancer in Japan is very low, but once they immigrate to the United States, their The offspring who grew up in the United States, the incidence of the disease is basically the same as that of Americans. Due to the huge changes in the meat in...

Claims

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Application Information

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IPC IPC(8): C07D305/14A61P35/00A61P13/08
Inventor 蔡强冉秀琼王旭阳徐信保王琼
Owner 无锡紫杉药业股份有限公司
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