多靶点受体酪氨酸激酶抑制剂ABT-869的有效合成方法
收稿日期: 2014-02-20
修回日期: 2014-03-06
网络出版日期: 2014-03-13
基金资助
河南省教育厅科学技术研究重点（Nos. 14A150052，12A150026）、郑州市科技攻关计划（No. 121PPTGG509-2）资助项目.
Synthesis of a Multiple Target Receptor Tyrosine Kinase Inhibitors ABT-869
Received date: 2014-02-20
Revised date: 2014-03-06
Online published: 2014-03-13
Supported by
Project supported by the Education Department of Henan Province Science and Technology Research Projects (Nos. 14A150052, 12A150026), the Scientific Research Plan of Zhenzhou (No. 121PPTGG509-2).
ABT-869是结构新型有效的多靶点受体酪氨酸激酶抑制剂，目前正处在III期临床研究阶段. 从商业廉价易得的间氟苯胺出发，以较低的成本经过7步反应以42.3%的总收率实现了多靶点受体酪氨酸激酶抑制剂ABT-869全合成. 该工艺在关键步骤Suzuki偶联反应中使用了超声波反应器，极大地缩短反应时间，提高了收率，并且该工艺各步反应中间体不用纯化直接投入下步反应，最终产物只需结晶纯化即可达到大于99%的纯度，无需传统的柱层析分离，更适合于工业生产.
关键词： 受体酪氨酸激酶抑制剂; ABT-869; 合成
侯学会 , 张京玉 , 刘宏民 . 多靶点受体酪氨酸激酶抑制剂ABT-869的有效合成方法[J]. 有机化学, 2014 , 34(6) : 1196 -1200 . DOI: 10.6023/cjoc201402025
An efficient and convenient protocol for the synthesis of ABT-869, which is a multiple target receptor tyrosine kinase inhibitors with novel structure and high inhibitory activity, was developed in seven steps from cheap and commercially available of 3-fluoroaniline. The target molecular was obtained in 42.3% overall yield without any traditional purification (column chromatography or crystallization). Ultrasonic reaction technology was introduced in the Suzuki coupling reaction which is the key step of the preparation of ABT-869. The synthetic process was more suitable for industrialized production due to the advantages of available starting material, simplicity and cheapness, well yield and purity (HPLC>99.0%).
Key words： receptor tyrosine kinase inhibitors; ABT-869; synthesis
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