| 抗肿瘤药物索拉非尼合成工艺的改进 |
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| 引用本文： | 陈静,王程鹏,何作鹏,姚建文.抗肿瘤药物索拉非尼合成工艺的改进[J].烟台大学学报(自然科学与工程版),2012,25(2):146-149. |
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| 作者姓名： | 陈静 王程鹏 何作鹏 姚建文 |
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| 作者单位： | 烟台大学药学院,山东烟台,264005 |
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| 摘 要： | 以2-吡啶甲酸（2）为起始原料，经氯化、酯化一锅法合成高纯度的中间体（4），中间体（4）经酰胺化得到中间体（5），（5）在TBAB和氢氧化钠存在下，与对氨基苯酚亲核取代成醚得到中间体（6）；3-三氟甲基-4-氯苯胺（7）和三光气反应，经减压蒸馏纯化得到相应的异氰酸酯（8）；（6）与4--氯-3-三氟甲基苯异氰酸酯（8）缩合制得索拉非尼（1）．改进后的合成工艺总收率达69．7％，生产成本低，环境友好，操作简单且易于工业化生产．
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| 关 键 词： | 索拉非尼 多激酶抑制剂 异氰酸酯 抗肿瘤药物 合成 |
Improved Synthesis of Antitumor Drug Sorafenib |
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| CHEN Jing
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WANG Cheng-peng
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HE Zuo-peng
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YAO Jian-wen.Improved Synthesis of Antitumor Drug Sorafenib[J].Journal of Yantai University(Natural Science and Engineering edirion),2012,25(2):146-149. |
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| Authors: | CHEN Jing WANG Cheng-peng HE Zuo-peng YAO Jian-wen |
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| Institution: | (School of Pharmacy,Yantai University,Yantai 264005,China) |
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| Abstract: | The intermediate methyl 4-chloropicolinate(4) is prepared from picolinic acid(2) as a starting material by chloration and esterification.Its amidation afford 4-chloro-N-methylpicolinamide(5) which is converted into key intermediate 4-(4-aminophenoxy)-N-methylpicolinamide(6) by aromatic nucleophilic substitution with 4-aminophenol.4-chloro-3-(trifluoromethyl)phenylisocyanate(8) is obtained from 4-chloro-3-trifluoromethylaniline(7) by isocyanation with triphosgene.The synthesis of title compound is completed by the condensation of intermediate(6) with(8).This process has the features of cheap material,simple operation,high yield and green chemistry. |
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| Keywords: | sorafenib muti-kinase inhibitor isocyanate antitumor drug synthesis |
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