Method for preparing second-generation taxol anticancer drug Cabazitaxel

An anticancer drug, a technology for paclitaxel, which is applied in the field of preparing the second-generation paclitaxel anticancer drug Cabazitaxel, can solve the problems of long route, difficult purification, long synthesis route and the like, and achieves the advantages of simple preparation process, simple purification process and easy operation. Effect

Inactive Publication Date: 2013-04-03
FUDAN UNIV +1
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Problems solved by technology

[0011] The disadvantage of this method is that the route is too long, and the C-7 hydroxy methyl etherification conversion rate of the mother nucleus is low, and the total yield is less than 10%, which is not suitable for large-scale industrial preparation of XRP6258
[0012] The above two methods for preparing XRP6258 have defects such as low yield, difficult purification (multi-step column chromatography), and too long synthetic route, which limit industrial large-scale preparation and application to a certain extent.

Method used

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  • Method for preparing second-generation taxol anticancer drug Cabazitaxel
  • Method for preparing second-generation taxol anticancer drug Cabazitaxel
  • Method for preparing second-generation taxol anticancer drug Cabazitaxel

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Embodiment 1

[0046] Preparation of compound II

[0047]

[0048] 10-DAB(I) (27.3g, 50.0mmol) was dissolved in dry DMSO (200mL), acetic anhydride (200mL) was added, protected by argon, stirred at room temperature overnight, and after the reaction was detected by thin layer chromatography, the reaction solution was Concentrate under reduced pressure and evaporate to dryness, dilute the resulting residue with ethyl acetate (1.5L), and wash with saturated sodium bicarbonate solution (300mL×6), distilled water (200mL×3), and saturated aqueous sodium chloride solution (200mL×3) successively , dried over anhydrous sodium sulfate, and concentrated to obtain light yellow foamy solid product II (30.2 g, yield about 91.8%), which was directly carried out to the next step without purification; 1 H-NMR (400MHz, CDCl 3 ): δ8.06(d, 2H, J=7.0Hz, Ph-H), 7.62(t, 1H, J=7.6Hz, Ph-H), 7.49(t, 2H, J=7.6Hz, Ph-H ), 5.80(s, 1H, H-10), 5.67(d, 1H, J=6.7Hz, H-2), 4.94(d, 1H, J=9.2Hz, H-5), 4.84(d, 1H , J=11.6...

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Abstract

The invention belongs to the field of medicament synthesis, and relates to a method for synthesizing a second-generation taxol anticancer drug Cabazitaxel. The method comprises obtaining a key intermediate (II): a 10-deacetyl baccatin III (I) with C-7 and C-10 hydroxy-methylthio-methylene and C-13 hydroxy-oxidization, completing a de-methylthio operation for C-13 carbonyl and C-7 and C-10 methylthio methylene (MTM) of the compound II by a one-pot method to obtain a nucleus (IV) of an XRP6258, connecting the nucleus with various side chains, and then removing side chain protecting groups to obtain the product Cabazitaxel (V). The method has advantages of high efficiency in the preparation process, simple process, high yield, relatively low cost and easy operation, and is suitable for large-scale production and preparation of anti-cancer drugs XRP6258.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and relates to a method for synthesizing the second-generation paclitaxel anticancer drug Cabazitaxel (XRP6258), in particular to a method for synthesizing XRP6258 (V) with 10-deacetylbaccatin III (I) as a starting material A new method, the method has the advantages of high preparation process efficiency, simple process, high yield, low cost, easy operation, etc., and is suitable for large-scale production and preparation of anticancer drug XRP6258. Background technique [0002] Paclitaxel, the star molecule of anti-tumor drugs in the world today, is mainly used clinically for the treatment of ovarian cancer, esophageal cancer, metastatic urothelial cancer, squamous cell carcinoma of the head and neck, breast cancer, non-small cell lung cancer, malignant black solid tumor and some other solid tumors, especially for the treatment of metastatic ovarian cancer and breast cancer, it has been recognized...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/14
CPCY02P20/55
Inventor 李英霞刘珂王军飞丁宁张伟
Owner FUDAN UNIV
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