5442-91-1Relevant articles and documents
Preparation method of sunitinib intermediate
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Page/Page column 4-6, (2019/05/04)
The invention discloses a preparation method of a sunitinib intermediate. The method includes the following steps of 1, synthesis of 2, 4-dimethylpyrrole-3, 5-diethyl dicarboxylate, 2, synthesis of 4-ethoxycarbonyl-3, 5-dimethylpyrrole-2-carboxylic acid, 3, synthesis of 2, 4-dimethyl-3-ethyl pyrrole-2-carboxylate, 4, synthesis of 2, 4-dimethyl-5-aldehyde-1H-pyrrole-3-ethyl formate, and 5, synthesis of 2,4-dimethyl-5-aldehyde-1H-pyrrole-3-carboxylic acid. The method has the advantages that the raw materials are cheap, the environmental pollution is small, the industrial production is easy to achieve, the processing steps are fewer, the operation is simple, the reaction yield is very high, the mass production of enterprise is facilitated, and application and popularization are facilitated.
A Benzisoelenazolone modified pyrrole methyl ester substituted indole ketone compound and use thereof
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Paragraph 0295-0297, (2016/10/08)
The invention discloses a benzisoselenazolone-modified pyrrolyl formate-substituted indolone compound and a use thereof. The invention depends on and claims the priority of a Chinese patent application 201110105248.0 submitted on April 26, 2011. Through reference, all contents of the Chinese patent application 201110105248.0 are incorporated into the invention. The benzisoselenazolone-modified pyrrolyl formate-substituted indolone compound is shown in the general formula I. The 2-indolone compound provided by the invention has excellent antitumor activity and can be widely used for preparation of antitumor drugs.
An improved synthesis of sunitinib malate via a solvent-free decarboxylation process
Meng, Ge,Liu, Chunyan,Qin, Shidong,Dong, Mengshu,Wei, Xiaomi,Zheng, Meilin,Qin, Liwen,Wang, Huihui,He, Xiaoshuang,Zhang, Zhiguo
, p. 8941 - 8954 (2015/10/28)
To search for an economical and convenient synthesis of sunitinib and its malate salt, optimization of a scalable synthetic route was explored by designing a standard experimental protocol on laboratory scale using commercially available materials including acetyl ethyl acetate, 4-fluoroaniline, and N 1,N 1-diethylethane-1,2-diamine. The optimal conditions were established based on investigating the main reaction steps, including cyclization, hydrolysis, decarboxylation, formylation, and condensation, giving optimized yields for each step of 94.4, 97.6, 98.5, 97.1, 91.0, 86.3, 85.5, 88.2, 99.1, 97.3, and 58.7 %, respectively. The synthesis process of 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid as the important intermediate was significantly improved by using solvent-free decarboxylation instead of the traditional process in a high-boiling-point solvent. The subsequent formylation was conducted directly using the dichloromethane solution of the crude product from decarboxylation, leading to an almost quantitative combined yield of these two steps. The overall yields of sunitinib and its salt using the optimal synthesis process were 67.3 and 40.0 % based on acetyl ethyl acetate. The obtained data could be used as reference for future industrialization, especially for avoiding expensive solvents and reducing reaction time.
