Novel method for synthesizing sorafenib

Abstract

The invention discloses a novel method for synthesizing sorafenib. The method comprises the following steps: using a (4-(4-aminophenoxy)-N-methylpyridine-2-carboxamide) compound II and a (4-chloro-3-trifluoromethylphenyl-carbamoyl-imidazole) compound III as raw materials, and reacting in an organic solvent inert to the compound III to produce a sorafenib crude product; then, dissolving the sorafenib crude product by the organic solvent and an organic or inorganic acid, and adding a solvent into which sorafenib is difficult to dissolve to enable the sorafenib to be separated out, so as to obtain a sorafenib pure product. The novel method is simple in technical process, ensures high product purity, facilitates operation and is suitable for large-scale industrial production.

Description

technical field [0001] The present invention relates to the technical field of preparation of pharmaceutical compounds, in particular to the technical field of Sorafenib preparation, and more specifically, to a synthesis method and a purification method of Sorafenib. Background technique [0002] Compound 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide, also known as Rafenib, the molecular formula is C 21 h 16 CIF 3 N 4 o 3 , the molecular weight is 464.83, and the structural formula is formula Ⅰ. [0003] [0004] Sorafenib is a multikinase inhibitor indicated for the treatment of gastrointestinal stromal tumors and metastatic renal cell carcinoma that do not respond to or are intolerant to standard therapy. Sorafenib has dual anti-tumor effects: on the one hand, it can directly inhibit tumor growth by inhibiting the RAF / MEK / ERK signaling pathway; on the other hand, it can block tumor angiogenesis by inhibiti...

AI Technical Summary

Problems solved by technology

[0007] The reaction needs to be carried out at a high temperature of 90°C, and the reaction time is as long as 5 hours. The reaction of the 4-chloro-3-trifluoromethylphenyl isocyanate used is too violent and difficult to control

[0008] Chinese patent CN101671299A discloses a preparation method of sorafenib, the reaction raw material uses the highly toxic compound phenyl chloroformate, the industrial production is dangerous and not friendly to the environment

[0011] Although the existing technology can synthesize Sorafenib, there are generally disadvantages such as high temperature reaction, use of highly toxic raw materials, and uncontrollable reaction.

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