Dejun Zhou, Keyang Wang, Yuying Zhang, Xiaoyue Liu, Xiaoxia Mao
{"title":"Synthesis and Characterization of 3-S-impurities in Timolol Maleate.","authors":"Dejun Zhou, Keyang Wang, Yuying Zhang, Xiaoyue Liu, Xiaoxia Mao","doi":"10.2174/0115701794344307241027093947","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Timolol maleate is clinically used for the treatment of hypertension, angina pectoris, tachycardia, and glaucoma.</p><p><strong>Objective: </strong>The aim of this study was to enhance the safe use of timolol maleate and investigate a synthesis method for 3-S-timolol, a newly identified impurity in timolol API (Active Pharmaceutical Ingredients).</p><p><strong>Methods: </strong>(S)-3-(tert-butylamino)propane-1,2-diol (1) was used as a raw material. 3-S-timolol maleate (7) was synthesized through a five-step reaction. Overall yield was 57.7%, with a purity of 98%.</p><p><strong>Results: </strong>The structure of the target compound was confirmed <i>via</i> analysis of its <sup>1</sup>H nuclear magnetic resonance, <sup>13</sup>C nuclear magnetic resonance, and high-resolution mass spectrometry spectra.</p><p><strong>Conclusion: </strong>The synthesis method was straightforward and yielded a high-purity product suitable for use as a reference in the analysis and identification of timolol maleate-related substances.</p>","PeriodicalId":11101,"journal":{"name":"Current organic synthesis","volume":" ","pages":"614-619"},"PeriodicalIF":2.5000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current organic synthesis","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.2174/0115701794344307241027093947","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Timolol maleate is clinically used for the treatment of hypertension, angina pectoris, tachycardia, and glaucoma.
Objective: The aim of this study was to enhance the safe use of timolol maleate and investigate a synthesis method for 3-S-timolol, a newly identified impurity in timolol API (Active Pharmaceutical Ingredients).
Methods: (S)-3-(tert-butylamino)propane-1,2-diol (1) was used as a raw material. 3-S-timolol maleate (7) was synthesized through a five-step reaction. Overall yield was 57.7%, with a purity of 98%.
Results: The structure of the target compound was confirmed via analysis of its 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and high-resolution mass spectrometry spectra.
Conclusion: The synthesis method was straightforward and yielded a high-purity product suitable for use as a reference in the analysis and identification of timolol maleate-related substances.
背景：马来酸替马洛尔在临床上用于治疗高血压、心绞痛、心动过速和青光眼。目的：为提高马来酸噻洛尔的安全性，研究噻洛尔原料药中新发现的杂质3- s -噻洛尔的合成方法。方法：以(S)-3-（叔丁基氨基）丙烷-1,2-二醇(1)为原料。通过五步反应合成了3- s -马来酸噻咪洛尔(7)。总收率为57.7%，纯度为98%。结果：通过1H核磁共振、13C核磁共振和高分辨率质谱分析，确定了目标化合物的结构。结论：该合成方法简单，纯度高，可作为马来酸替马洛尔相关物质分析鉴定的参考。
期刊介绍：
Current Organic Synthesis publishes in-depth reviews, original research articles and letter/short communications on all areas of synthetic organic chemistry i.e. asymmetric synthesis, organometallic chemistry, novel synthetic approaches to complex organic molecules, carbohydrates, polymers, protein chemistry, DNA chemistry, supramolecular chemistry, molecular recognition and new synthetic methods in organic chemistry. The frontier reviews provide the current state of knowledge in these fields and are written by experts who are internationally known for their eminent research contributions. The journal is essential reading to all synthetic organic chemists. Current Organic Synthesis should prove to be of great interest to synthetic chemists in academia and industry who wish to keep abreast with recent developments in key fields of organic synthesis.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
