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The development of an effective synthetic route of rilpivirine
BMC Chemistry ( IF 4.6 ) Pub Date : 2021-04-01 , DOI: 10.1186/s13065-021-00749-y
Tao Zhang , Jiapei Yang , Zhongxia Zhou , Zhipeng Fu , Srinivasulu Cherukupalli , Dongwei Kang , Peng Zhan , Xinyong Liu

Rilpivirine (RPV) was approved by the U.S. FDA (Food and Drug Administration) in 2011 to treat individuals infected with human immunodeficiency virus 1 (HIV-1). Significantly, rilpivirine is three fold more potent than etravirine. Once-daily, it is used with a low oral dose (25 mg/tablet), decreasing the drug administration and bringing a better choice to the patients. However, there are many shortcomings in the existing synthesis route of RPV, such as the high cost, prolonged reaction time and low yield (18.5%). This article describes our efforts to develop an efficient and practical microwave-promoted method to synthesize rilpivirine using less toxic organic reagents and low boiling solvents. The last step's reaction time decreased from 69 h to 90 min through this optimized synthetic procedure, and the overall yield improved from 18.5 to 21%. In addition, the yield of intermediate 3 increased from 52 to 62% compared to the original patent. Overall, through a series of process optimization, we have developed a practical synthesis method of rilpivirine, which is easy to scale with higher yield and shorter reaction time.

中文翻译:

开发一种有效的利哌韦林合成途径

Rilpivirine(RPV)于2011年获得美国FDA(食品和药物管理局)的批准,用于治疗感染了人类免疫缺陷病毒1(HIV-1)的个体。值得注意的是,利匹韦林的效力比伊曲韦林高三倍。每天一次,口服剂量低(25毫克/片),减少了药物的使用,为患者带来了更好的选择。然而,现有RPV的合成路线存在许多缺点,例如成本高,反应时间长和产率低(18.5%)。本文介绍了我们的工作,以开发一种有效且实用的微波促进方法,以使用毒性较小的有机试剂和低沸点溶剂来合成利匹韦林。通过这种优化的合成程序,最后一步的反应时间从69 h减少到90 min,总收率从18.5%提高到21%。此外,与原始专利相比,中间体3的产率从52%增加到62%。总体而言,通过一系列工艺优化,我们开发了一种实用的利比韦林合成方法,该方法易于规模化,收率更高,反应时间更短。
更新日期:2021-04-02
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