Preparation method for cabazitaxel

A cabazitaxel and compound technology, applied in the field of preparation of cabazitaxel, can solve the problems of complex process, harsh reaction conditions, low yield and the like, and achieve the effects of simple process, low cost and high yield

Active Publication Date: 2012-01-11
SHANGHAI HENGHE MEDICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, the main process for synthesizing cabazitaxel is the patented synthesis process of Sanofi-Aventis, which uses 10-DABIII (10-deacetylbaccatin III) as raw material, and selects the hydroxyl groups at the 7-position and 10-position 7,10-dimethoxy-10-DABIII is obtained after methylation, and then the target product cabazitaxel (7,10-dimethoxy poly Sitaxel), this process has applied for a patent, the process is complex, the reaction conditions are harsh, and the yield is low

Method used

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  • Preparation method for cabazitaxel
  • Preparation method for cabazitaxel
  • Preparation method for cabazitaxel

Examples

Experimental program
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Effect test

Embodiment 1

[0042] Example 1 Preparation of Cabazitaxel

[0043] A preparation method of cabazitaxel, the route of synthesizing cabazitaxel is to use compound 1 (as shown in the reaction formula) as a raw material, the protective groups at positions 7 and 10 are removed, and then double methylation, and finally 13 The side chain is hydrolyzed to open the ring to obtain compound 4 Cabazitaxel.

[0044] Specifically include the following steps:

[0045] (1) Compound 1 is deprotected to release the hydroxyl groups at positions 7 and 10 to synthesize compound 2.

[0046] Take a 2.0L three-necked bottle, add 750mL of methanol and 120mL of acetic acid, heat the solution to 45°C, add compound 1 (100g) and zinc powder (60g) to the above solution, and react for about 5min. Filter, pour the filtrate into cooled water, stir, and a large amount of white solid is precipitated, which is filtered to obtain a white solid, which is dissolved in ethyl acetate with NaHCO 3 The solution was adjusted to ne...

Embodiment 2

[0061] Example 2 Test for the purity of cabazitaxel

[0062] The purity of compound 4 was tested by HPLC as Figure 13 shown and shown in Table 1, Figure 13 HPLC for the purity test of compound 4.

[0063] Table 1 Parameters of the HPLC spectrum of the product purity prepared by the present invention

[0064]

[0065] In patent US5847170A, the synthetic method of cabazitaxel is reported, but the steps are cumbersome. It takes 10-DAB (III) as the initial raw material, and uses trimethylsilicon to protect the 7 and 13 hydroxyl groups first and then carry out the methylation of the 10 position. , then remove the 7 and 13 protecting groups, then methylate the 7-position hydroxyl, and finally couple with the side chain and open the ring to obtain the product cabazitaxel, and the total weight yield is less than 20% (with 10-DAB (III) ) is the raw material), because the steps are cumbersome, the used raw materials, solvents and various energy consumptions are extremely large, ...

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Abstract

The invention relates to a preparation method for cabazitaxel. The method comprises that: (1) a compound 1 is subjected to deprotection to release hydroxyl groups positioned on the site 7 and the site 10; (2) a side chain is linked to the site 13 of taxane, then the dual methylation treatment is performed for the site 7 and the site 10 of the taxane; (3) the side chain positioned on the site 13 is subjected to ring opening to obtain a compound 4, wherein the compound 4 is the cabazitaxel. The reaction formula is as follow. The raw materials used in the method provided by the present invention are simple and easy to be obtained; the new process adopts the three-step reaction, and is simple; the yield is high; the cost is low; the prepared product has high purity, wherein the purity can reach more than 99.5%.

Description

technical field [0001] The invention belongs to the field of medical engineering, in particular to a preparation method of cabazitaxel. Background technique [0002] Cabazitaxel [English name Cabazitaxel (JEVTANA)] is a taxane compound, similar in structure to the anticancer drugs paclitaxel and docetaxel. [0003] On June 17, 2010, the US Food and Drug Administration (FDA) approved Sanofi-Aventis' new drug cabazitaxel (Jevtana) in combination with prednisone (Prednisone) for the treatment of advanced prostate cancer. Cabazitaxel is the first drug of choice for the treatment of advanced, hormone-resistant prostate cancer when docetaxel, a commonly used advanced prostate cancer drug, is ineffective or worsened. Cabazitaxel, a novel treatment for castration-resistant prostate cancer patients, has given hope to patients with prostate cancer, albeit with only moderate gains, confirming the efficacy of prostate cancer immunotherapy. Therapeutic strategies entering the Phase III...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/14
Inventor 张伟中张爱平王权勇尹中船黄武蔡志香仝泽彬高卅
Owner SHANGHAI HENGHE MEDICAL TECH
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