Cabazitaxel crystal and preparation method thereof

A technology of crystal and docetaxel, applied in the field of cabazitaxel crystal and its preparation, can solve the problems of harsh reaction conditions, complicated process, influence of the purity of cabazitaxel, etc.

Active Publication Date: 2012-09-19
SHANGHAI JINHE BIO TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] 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), the process has been patented, the process is complicated, the reaction conditions are harsh, and the yield is low
[0006] Cabazitaxel exists in a variety of crystal forms. In the US patent US2005065138A1, a crystal form of acetonate was applied for, and the Chinese patent CN101918385A involved five anhydrous forms and some corresponding ethanolate forms. However, in the patent The crystal form of the anhydrous form is obtained at high temperature, which will affect the purity of cabazitaxel

Method used

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  • Cabazitaxel crystal and preparation method thereof
  • Cabazitaxel crystal and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 1. Dissolve 5 g of Cabazitaxel powder in 30 ml of acetone (frozen to 0°C), then slowly add the resulting solution dropwise (about 20 min) into 390 ml of distilled water (frozen to 0-3°C) while stirring, Continue to stir for 30 min after the dropwise addition, and filter with suction to obtain a white powder.

[0032] 2. The obtained white powder was dried under reduced pressure (vacuum 10-20 Pa) at room temperature for 48 h to obtain 4.4 g of white powder.

[0033] 3. Dissolve 4.5 g of the white powder obtained in operation 2 in 30 ml of acetone (frozen to 0°C), and slowly add the resulting solution dropwise (about 20 min) to 390 ml of distilled water (frozen to 0-3°C) while stirring After the dropwise addition, continue to stir for 30 min, and filter with suction to obtain a white powder.

[0034] 4. The obtained white powder was dried under reduced pressure (vacuum 10-20 Pa) at room temperature for 48 h to obtain 4.1 g of white powder with a yield of 82% wt and a pur...

Embodiment 2

[0036] 1. Dissolve 10 g of Cabazitaxel powder in 60 ml of acetone (frozen to 0°C), then slowly add the resulting solution dropwise (about 30 min) into 780 ml of distilled water (frozen to 0-3°C) while stirring, Continue to stir for 30 min after the dropwise addition, and filter with suction to obtain a white powder.

[0037] 2. The obtained white powder was dried under reduced pressure (vacuum 10-20 Pa) at room temperature for 48 h to obtain 9 g of white powder.

[0038] 3. Dissolve 9 g of the white powder obtained in operation 2 in 60 ml of acetone (frozen to 0°C), and slowly add the solution dropwise (about 30 min) to 780 ml of distilled water (frozen to 0-3°C) while stirring. After the dropwise addition, continue to stir for 30 min, and filter with suction to obtain a white powder.

[0039] 4. The obtained powder was dried under reduced pressure (vacuum 10-20 Pa) at room temperature for 48 h to obtain 8.5 g of white powder with a yield of 85% wt and a purity of 99.80 % wt....

Embodiment 3

[0042] 1. Dissolve 100 g of Cabazitaxel powder in 600 ml of acetone (frozen to 0°C), and slowly add the resulting solution dropwise (about 90 min) to 7800 ml of distilled water (frozen to 0-3°C) while stirring, After the dropwise addition, continue to stir for 50 min, and filter with suction to obtain a white powder.

[0043] 2. The obtained white powder was dried under reduced pressure (vacuum 10-20 Pa) at room temperature for 48 h to obtain 91 g of white powder.

[0044] 3. Dissolve 91 g of the white powder obtained in operation 2 in 600 ml of acetone (frozen to 0°C), and slowly add the resulting solution dropwise (about 90 min) to 7800 ml of distilled water (frozen to 0-3°C) while stirring After the dropwise addition, continue to stir for 50 min, and filter with suction to obtain a white powder.

[0045] 4. The obtained white powder was dried under reduced pressure (vacuum 10-20 Pa) at room temperature for 48 h to obtain 88 g of white powder with a yield of 88% wt and a puri...

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Abstract

The invention relates to a cabazitaxel crystal which is solvent-free and non-crystallization water crystal form of 7, 10-dimethoxy docetaxel or (2R, 3S)-3-tert-butoxycarbonyl amino-2-hydroxyl-3- phenylpropionic acid 4-acetoxyl-2 alpha-benzoyloxy-5 beta, 20-epoxy-1-hydroxyl-7 beta, 10 beta- dimethoxy-9-oxo-11-taxadiene-13 alpha-ester; and the cabazitaxel crystal is shown to be positioned at 4.3, 7.1, 8.7, 10.2, 10.9, 12.2, 13.8, 15.2, 16.4, 17.0, 17.6, 18.3, 19.2, 19.6, 20.3, 21.2, 23.1, 24.7, 26.1, 27.3, 29.3, 31.9, 32.5 and 35.8 degrees 2 theta characteristic peak by powder X ray diffraction (PXRD). The invention also discloses a preparation method of the cabazitaxel crystal. The cabazitaxel crystal is prepared under the condition of reduced pressure at the room temperature, and is high in yield and good in purity.

Description

technical field [0001] The present invention relates to the technical field of pharmacy, and relates to a cabazitaxel crystal and a preparation method thereof, in particular to a cabazitaxel or 7,10-dimethoxydocetaxel or (2R,3S)-3-tert Butoxycarbonylamino-2-hydroxy-3-phenylpropanoic acid 4-acetoxy-2α-benzoyloxy-5β, 20-epoxy-1-hydroxy-7β, 10β-dimethoxy- Crystalline form of 9-oxo-11-taxene-13α-yl ester and process for its preparation. Background technique [0002] Cabazitaxel [English name Cabazitaxel (JEVTANA)] is a taxane compound, which is similar in structure to the anticancer drugs paclitaxel and docetaxel. [0003] Cabazitaxel is a microtubule inhibitor suitable for use in combination with prednisone in the treatment of patients with metastatic prostate cancer previously treated with hormone-refractory docetaxel-containing regimens. The docetaxel-containing regimen, from the results of this trial, demonstrated that the combination of cabazitaxel and prednisone in patie...

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 JINHE BIO TECH
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