摘要
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.
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（HPLC99.0%）.
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2014年第6期1196-1200,共5页
Chinese Journal of Organic Chemistry
基金
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~~
