阿西替尼中间体(E)-6-碘-3-(2-(吡啶-2-基)乙烯基)-1-(四氢-2H-吡喃-2-基)-1H-吲唑的合成研究  

Study on Synthesis of(E)-6-Iodo-3-(2-(pyridine-2-yl)vinyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

作　　者：孟凡星[1] 张诗缇 蔡东[1] 贾云宏[1] 

机构地区：[1]辽宁医学院药学院,辽宁锦州121001

出　　处：《化学世界》2015年第6期366-369,共4页Chemical World

摘　　要：(E)-6-碘-3-(2-(吡啶-2-基)乙烯基)-1-(四氢-2 H-吡喃-2-基)-1 H-吲唑是阿西替尼的关键中间体,以6-硝基-1 H-吲唑为起始原料,经过碘代、加成、偶联、还原、碘代得到目标化合物。探讨了用微波辐射加热偶联反应的问题,并对各步反应合成条件进行了优化。改进后工艺总收率达42.32%(6-硝基-1 H-吲唑为原料计),收率比文献报道值提高近5%,目标化合物和各中间体经1 H NMR和MS等确证结构。改进后的工艺降低了成本,简单可行,适合工业化生产。（E）-6-Iodo-3-[2-（pyridin-g-yl）ethenyl]-l-（tetrahydro-2H-pyran-2-yl）-lH-indazole is the key in- termediate of axitinib, which is synthesized from 6-nitroindazole via iodination, addition, cross coupling, reduction and iodination reactions. Microwave-promoted Heck cross coupling reaction was investigated, and the reaction conditions of all steps were optimized. The total yield was about 42.32% which increased by 5% based on 3-methyl-6-nitroindazole. The product and its intermediates were confirmed by 1I-[ NMR and MS. Compared with the methods in patents, this method was more simple to operate with low cost and high yield and was also more suitable for large scale production.

关 键 词：阿西替尼 中间体 (E)-6-碘-3-[2-(吡啶-2-基)乙烯基]-1-(四氢-2 H-吡喃-2-基)-1 H-吲唑 工艺改进 

分 类 号：O626.4[理学—有机化学]