文献类型：期刊文献

中文题名：合成宾达利的新方法

英文题名：A New Mothod of Synthesizing Bindarit

作者：杜彩彦[1];黄伟彬[1];刘宏伟[1];廖道华[1];冀亚飞[1]

机构：[1]华东理工大学药学院,上海200237

年份：2013

卷号：21

期号：2

起止页码：129

中文期刊名：合成化学

外文期刊名：Chinese Journal of Synthetic Chemistry

收录：CSTPCD;;北大核心:【北大核心2011】；CSCD:【CSCD_E2013_2014】；

基金：国家自然科学基金资助项目(21176074)

语种：中文

中文关键词：宾达利;MCP-1抑制剂;吲唑;药物合成

外文关键词：Bindarit; MCP-1 inhibitor; indazole; drug synthesis

摘要：以邻氨基苯乙酮(2)为原料,经过连续的重氮化-还原-缩合反应序列制得3-甲基-1H-吲唑(3);3经(Boc)2O保护亚氨基后以NBS进行甲基溴代反应制得1-叔丁氧羰基-3-溴甲基-1H-吲唑(5);5与2-羟基异丁酸乙酯缩合得醚2-(1-叔丁氧羰基-1H-吲唑-3-基)甲氧基-2-甲基丙酸乙酯(6);6经HCl/乙酸乙酯溶液脱Boc保护制得关键中间体7;在叔丁醇钾存在下,7与溴苄缩合并水解合成了MCP-1抑制剂宾达利,总收率37.3%,其结构经1H NMR,13C NMR和MS确证。
3-methyl-lH-indazole（3） was prepared from o-aminoacetophenone（2） by a sequential di- / azotization-reduction-condensation sequence../3 was protected by （Boe）20 for its imino group, fol- lowed by methyl bromination with NBS to provide 1-Boc-3-bromomethyl-lH-indazole （5）. Then, the condensation of 5 with ethyl 2-hydroxyisobutyrate produced the corresponding ether ethyl 2-（ 1-Boc- 1H-indazole-3-yl） methoxy-2-methylpropionate （ 6）, which was further performed a concluding Boc re- moval in HC1/EtOAe solution to obtain the key intermediate 7. In the presence of potassium tert-bu- toxide, 7 was condensed with benzyl bromide and simultaneously hydrolyzed to achieve MCP-1 inhibi- tor, Bindarit in an overall yield of 37.3%. The structures were confirmed by 1H NMR, 13C NMR and MS.