Cabazitaxel crystal and preparation method thereof

A technology of docetaxel and dimethoxy, which is applied in the field of cabazitaxel crystals and its preparation, can solve problems such as complex process, harsh reaction conditions, and influence on the purity of cabazitaxel, and achieve improved reaction efficiency and good purity Effect

Active Publication Date: 2013-01-30
SHANGHAI JINHE BIO TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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 anhydrous crystal forms are all obtained at high temperature, which will affect the purity of cabazitaxel, and each crystal form has solvent residues, which poses a hidden danger to the safety of the drug

Method used

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 1. Dissolve 4g of Cabazitaxel powder in 100ml of acetonitrile (heated to 30°C), then slowly add the resulting solution dropwise (about 20 minutes) into 1300ml of distilled water (frozen to 0-3°C, with a certain stirring speed), drop Stirring was continued for 30 minutes after addition, and white powder was obtained by suction filtration.

[0032] 2. The obtained white powder was dried under reduced pressure (vacuum 10-20 Pa) at room temperature for 48 hours to obtain 3.7 g of white powder.

[0033] 3. Dissolve 3.7g of the white powder obtained in operation 2 in 100ml of acetonitrile (heated to 30°C), then slowly add the resulting solution dropwise (about 20min) to 1300ml of distilled water (frozen to 0-3°C, with a certain stirring speed) After the dropwise addition, continue to stir for 30 minutes, and filter with suction to obtain a white powder.

[0034] 4. The resulting white powder was dried under reduced pressure (vacuum 10-20 Pa) at room temperature for 48 hours ...

Embodiment 2

[0036] 1. Dissolve 40g of Cabazitaxel powder in 1L of acetonitrile (heated to 30°C), then slowly add the resulting solution dropwise (about 2h) to 13L of distilled water (frozen to 0-3°C, with a certain stirring speed) while stirring , continued to stir for 30 min after the dropwise addition, and filtered 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 hours to obtain 37.4 g of white powder.

[0038] 3. Dissolve 37.4g of the white powder obtained in operation 2 in 1L of acetonitrile (heated to 30°C), then slowly add the resulting solution dropwise (about 2h) to 13L of distilled water (frozen to 0-3°C, stirring regularly) speed), continue to stir for 30 minutes after the dropwise addition, 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 hours to obtain 35.8 g of ...

Embodiment 3

[0041] 1. Dissolve 80g of Cabazitaxel powder in 2L of acetonitrile (heated to 30°C), then slowly add the resulting solution dropwise (about 3h) to 26L of distilled water (frozen to 0-3°C, with a certain stirring speed) while stirring , continued to stir for 30 min after the dropwise addition, and filtered with suction to obtain a white powder.

[0042] 2. The obtained white powder was dried under reduced pressure (vacuum 10-20 Pa) at room temperature for 48 hours to obtain 75.1 g of white powder.

[0043] 3. Dissolve 75.1g of the white powder obtained in operation 2 in 2L of acetonitrile (heated to 30°C), then slowly add the resulting solution dropwise (for about 3 hours) to 26L of distilled water (frozen to 0-3°C, stirring regularly) speed), continue to stir for 30 minutes after the dropwise addition, and filter with suction to obtain a white powder.

[0044] 4. The resulting white powder was dried under reduced pressure (vacuum 10-20 Pa) at room temperature for 48 hours to ...

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Abstract

The invention relates to a solvate-free and crystal water-free crystal form of 4-accetoxy-2alpha-benzoyloxy-5beta,20-epoxy-1-hydroxy-7beta,10beta-dimethoxy-9-oxotax-11-en-13alpha-yl(2R,3S)-3tert-butoxycarbonylamino-2-hydroxy-3-phenylpropanoate 1-hydroxy-7beta,10beta-dimethoxy-9-oxo-5beta,20-epoxytax-11-ene-2alpha,4,13alpha-triyl4-acetate 2-benzoate13-[(2R,3S)-3-{[(tertbutoxycarbonyl]amino}-2-hydroxy-3-phenylpropanoate. A powder X-ray diffraction (PXRD) diagram shows that the crystal is positioned on the characteristic peaks of 4.3, 7.4, 8.6, 10.0, 11.0, 12.2, 12.6, 13.3, 13.6, 14.2, 15.0, 15.5, 16.4, 17.0, 18.1, 18.6, 20.2, 21.0, 21.6, 22.1, 22.8, 24.0, 24.6, 25.3, 25.8, 26.9, 28.0, 29.4, 31.5, 32.0, 34.4, 35.5, 36.8 and 41.7 DEG 2theta. The invention also discloses a preparation method for the crystal. The crystal prepared under reduced pressure at room temperature is high in yield and purity, and does not have any solvent residue.

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] 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 patients with m...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/14
CPCC07D305/14
Inventor 张伟中张爱平王权勇仝泽彬高卅蔡志香尹中船黄武
Owner SHANGHAI JINHE BIO TECH
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