Preparation process and structure confirmation of impurity C of rupatifen fumarate

LI Lin; WANG Xiaoming; MENG Shufang; CHEN Lin; WANG Haiyan; LIN Pengfei; CHEN Ling

doi:10.11665/j.issn.1000-5048.20200504

Journal of China Pharmaceutical University > 2020 > 51(5): 530-537. > DOI: 10.11665/j.issn.1000-5048.20200504

LI Lin, WANG Xiaoming, MENG Shufang, CHEN Lin, WANG Haiyan, LIN Pengfei, CHEN Ling. Preparation process and structure confirmation of impurity C of rupatifen fumarate[J]. Journal of China Pharmaceutical University, 2020, 51(5): 530-537. DOI: 10.11665/j.issn.1000-5048.20200504

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Preparation process and structure confirmation of impurity C of rupatifen fumarate

Funds: This study was supported by China National Key Hi-Tech Innovation Project for the R&D of Novel Drugs(No.2018ZX09J18108-005) and Fujian Provincal Science and Technology Major Special Project(No.2015YZ0002-2)

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Received Date: November 24, 2019
Revised Date: August 09, 2020

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Abstract

The high-purity impurity C was isolated and purified from a new anti-allergic drug, rupatifen, by nucleophilic substitution reaction with bromobutaric acid, and its structure was confirmed by IR, UV, MS, ¹H NMR, ¹³C NMR, DEPT135°,HSQC, HMBC, and ¹H-¹HCOSY. The preparation process of impurity C in this study was simple and easy to obtain under mild conditions, with the purity of 99.0% and the yield of 25%-30%;and the sample met the target compound by structural confirmation. The preparation process and structure confirmation provided sufficient impurity C reference substance for impurity research of raw materials and preparations of rupatifen fumarate, which laid a solid foundation for quality research of new drugs.
- rupatifen fumarate,
- impurity C,
- preparation process,
- structure confirmation,
- nuclear magnetic resonance,
- high resolution mass spectrometry

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[1]	.2016-06-01.
[2]	Fujian Mindong Rejuvenation Pharmaceutical Co.，Ltd.Rupatifen fumarate impurity C， preparation method and detection method thereof：CN， 201811043105.X［P］.2019-01-11.
[3]	Wang C， Zhou MQ， Huang WC. Separation and structural confirmation of 5-methoxybenzo［d］oxazole-2（3H）-thione from key intermediate of omeprazole［J］. Chin J Synth Chem（合成化学）， 2018， 26（4）：284?287.
[4]	CFDA.The technical guidelines for the preparation and structural confirmation of chemical drug apis［EB/OL］.（2007-08-23）［2019-10-20］.http：//www.cde.org.cn/zdyz.do？method=largePage &id=2067.
[5]	ICH.Impurities in new drug substances（Q3A）［EB/OL］.（2006-10-25）［2019-10-21］.https：//www.ich.org/page/quality-guidelines.
[6]	Compania Uriach Y.Rupatadine salt as an antihistaminic agent：CN， 201180030958. X［P］.2013-03-06［2019-10-20］.
[7]	Li LL.Study on the synthesis and impurity of rupatadine fumarate （富马酸卢帕他定的合成及杂质研究）［D］.Hangzhou：Zhejiang University，2015.
[8]	Zhao X.synthesis The，structure confirmation and qualitative analysis of rupatadine fumarate （富马酸卢帕他定的化学合成、结构确证和质量分析）［D］.Jinan： Shandong University，2008.
[9]	Hu CQ，Zhang X.Current situation and the trend in impurity profiling of chemical drugs［J］.Acta Pharm Sin（药学学报），2019，54（12）：2214?2231.

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Preparation process and structure confirmation of impurity C of rupatifen fumarate

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