实验研究盐酸维拉佐酮的合成工艺改进研究.PDFVIP

现代药物与临床 Drugs Clinic 第 32 卷 第 3 期 2017 年 3 月 ·361 · • 实验研究 • 盐酸维拉佐酮的合成工艺改进研究 康江鹏，潘 毅，陈 蔚，陶 勇 天津药物研究院 化学原料药研究中心，天津 300193 摘 要：目的 对盐酸维拉佐酮的合成工艺进行改进。方法 以 4-(4- 乙酰基哌嗪-1-基)苯酚为起始原料，经 Duff 反应、取 代、环化、脱保护、酰胺化得到关键中间体 5-(1-哌嗪基)-苯并呋喃-2- 甲酰胺，再与3-(4-氯丁酰基)-1H-吲哚-5- 甲氰缩合、成 盐得到盐酸维拉佐酮。结果 合成了目标化合物盐酸维拉佐酮，并利用 1H-NMR 、MS 确证了结构，质量分数为 99.8%，该 路线的总收率为 22.5% 。结论 该合成工艺原料廉价易得、操作简单，适于工业化生产。 关键词：盐酸维拉佐酮；合成工艺；Duff 反应；工业化生产 中图分类号：R914 文献标志码：A 文章编号：1674 - 5515(2017)03 - 0361 - 04 DOI: 10.7501/j.issn.1674-5515.2017.03.001 Improvement of synthetic process of vilazodone hydrochloride KANG Jiang-peng, PAN Yi, CHEN Wei, TAO Yong Research Center of Chemical Raw Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China Abstract: Objective To improve the process for synthesis of vilazodone hydrochloride. Methods The key intermediate 5-(1- piperazinyl)benzofuran-2-carboxamide was prepared from 4-(4-acetylpiperazine-1-yl)phenol by Duff reaction, substitution, cyclization, deprotection, and amidation. Vilazodone hydrochloride was synthesized from 5-(1-piperazinyl)benzofuran-2-carboxamide and 3-(4-chlorobutyryl)-1H-indole-5-carbonitrile by substitution and salification. Results The target compound vilazodone hydrochloride was synthesized and characterized by 1H-NMR and MS. The purity was 99.8%, and the total yield of this synthetic route was 22.5%. Conclusion The synthetic process with facile material and simple operation simplified method is applicable to industrial production. Key words: vilazodone hydrochloride; synthetic process; Duff reaction; industrial production 盐酸维拉佐酮是美国 Trovis Pharmaceuticals 苯并呋喃-2- 甲酸乙酯经过还原得到 5-氨基苯并呋 LLC 公司研制的具有双重作用的选择性 5-羟色胺 喃-2- 甲酸乙酯，然后与双(2-氯乙基)胺缩合得到 （5-HT ）再摄取抑制剂和5-HT1