摘要
为了解决目前宾达利(BIN)合成工艺难放大生产的问题,报道了一种高效制备BIN的方法。以吲唑-3-羧酸为起始原料,经酯化反应得到吲唑-3-羧酸甲酯(Ⅰ),该中间体与苄溴反应得到1-苄基吲唑-3-羧酸甲酯(Ⅱ),随后酯基进一步被硼氢化钠还原得到1-苄基吲唑-3-甲醇(Ⅲ)。最后中间体Ⅲ与氯仿、丙酮在碱性条件下反应得到目标产物BIN,通过^(1)HNMR、^(13)CNMR、HRMS和元素分析对BIN结构进行了表征。在n(Ⅲ)∶n(Na OH)∶n(CHCl;)=1∶10∶4,反应温度为55℃,反应时间为3 h的最佳反应条件下,BIN产率为65.0%。该法步骤简单,原料廉价易得,易于工业化生产。
In order to solve the problem that bindarit (BIN) synthesis process is difficult to industrially produce,an efficient method for the synthesis of BIN was reported.Firstly,methyl 1H-indazole-3-carboxylate(Ⅰ) was prepared by esterification reaction of 1H-indazole-3-carboxylic acid.Then,the intermediateⅠreacted with benzyl bromide to obtain methyl 1-benzyl-1H-indazole-3-carboxylate (Ⅱ).Subsequently,the ester group of compoundⅡwas further reduced by sodium borohydride and converted to (1-benzyl-1H-indazol-3-yl)methanol (Ⅲ).Finally,the reaction of the intermediateⅢwith chloroform and acetone in the presence of sodium hydroxide led to the target product BIN.The structure of BIN was confirmed by~1HNMR,^(13)CNMR,HRMS and elemental analysis.Under the optimum conditions of n(Ⅲ)∶n(NaOH)∶n(CHCl;)=1∶10∶4,reaction temperature of 55℃and reaction time of 3 h,the yield of BIN was 65.0%This method was characterized by simple and convenient operation,cheap and easily available raw materials and easy industrialized production.
作者
杨旭锋
闫玉兵
陈栋栋
YANG Xufeng;YAN Yubing;CHEN Dongdong(Department of Chemistry&Chemical Engineering,Lyuliang University,Lyuliang 033001,Shanxi,China)
出处
《精细化工》
EI
CAS
CSCD
北大核心
2022年第6期1223-1227,1276,共6页
Fine Chemicals
基金
山西省高等学校科技创新项目(2021L568,2019L0941)
吕梁市引进高层次科技人才重点研发项目(2019105)。
关键词
宾达利
吲唑-3-羧酸
单核细胞趋化蛋白-1抑制剂
酯基还原
硼氢化钠
医药原料
bindarit
1H-indazole-3-carboxylic acid
monocyte chemoattractant protein-1 inhibitor
ester group reduction
sodium borohydride
drug materials
作者简介
杨旭锋(1988-),男,博士,副教授,E-mail:yangxufeng2018@163.com。
