盐酸阿比朵尔合成工艺优化研究

The research on arbidol synthesis process optimization

目的改进盐酸阿比朵尔的合成方法。方法以1,2-二甲基-5-羟基-3-吲哚甲酸乙酯为起始原料,经酰化、溴化、缩合、Mannich反应、成盐5步反应,得到目标产物盐酸阿比朵尔,目标产物及各步中间体结构经LC-MS、~1H-NM R确证。结果与结论该合成工艺总收率为39.70%(以1,2-二甲基-5-羟基-3-吲哚甲酸乙酯计),较文献收率提高了5.1%,纯度大于99.9%,新工艺中不再使用一类溶剂四氯化碳和剧毒品苯硫酚,反应条件温和,适合工业化生产。

Influenza is an acute respiratory tract infection caused by influenza viruses and it remains a serious health concern. The antiviral activity of arbidol, a new antiviral agent, is most pronounced against influenza of the A and B antigenic type. In this paper, we optimized the synthetic process of arbidol hydrochloride （AH）. There is a problem of using highly toxic solvents and raw materials in the reference^3] method. On the basis of reference method, the reaction conditions such as reaction temperature and solvent were optimized. Arbidol hydrochloride was produced from 1,2-dimethyl-5-hydroxy-3-indolecarboxylate through acylation,bromination, condensation, Mannich reaction and salt formation. The structures of the produced and associated intermediates were validated by LCMS and 1H-N1VIR during the synthesis. With our optimized synthetic process,the purity of our product is more than 99.9% and the overall yield of AH is 39.70% （ calculated by the amount of ethyl 1,2-dimethyl-5-hydroxy-3-indolecarboxylate）, which was 5.1% higher than the reported yield in previous literatures. Additionally, toxic reagents such as carbon tetrachloride and thiophenol were not included in the optimized synthetic route. Therefore, we provided a milder synthetic strategy which is suitable for industrial production.