Microwave Reaction Improved Heterocyclization of Quinazolinone Ring in Synthesis of Erlotinib Analogues

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dc.contributor.authorMan, Jianghongen_US
dc.contributor.authorQi, Jianbinen_US
dc.contributor.authorJiang, Jieen_US
dc.contributor.authorLi, Shaen_US
dc.date.accessioned2020-11-18T10:29:11Z
dc.date.available2020-11-18T10:29:11Z
dc.date.issued2020-05
dc.description.abstractBackground Tinibs were a kind of important epidermal growth factor receptor (EGFR) inhibitors used aspotential therapeutic agents in treating non-small cell lung cancer (NSCLC) in clinic. The drug resistance ofclinical used tinibs made the development of more active tinib analogues an attractive field in research.Quinazoline ring was regarded as the key fragment in tinibs and quinazolinone was indispensible intermediatein the synthesis of quinazoline. Thus, synthesis of quinazolinone intermediates was a key step which wouldfurther limit the overall yield of final product of tinib analogues. However, the commonly used synthetic scheme was somewhat complicated and time consuming with relatively low yield in heterocylization ofquinazolinone and its derivatives.Aim In this work, we intended to explore an effective way to improve synthesis of heterocyclization of 6,7-bis(2-methoxyethoxy)quinazolin-4(3H)-one (compound 5), the key fragment of erlotinib analogues, in bothreaction procedure and yield, thus to provide reference to synthesis of other quinazolinone derivatives.Methods A simple microwave-assisted one-pot reaction was employed to improve the synthesis ofheterocyclization of quinazolinone ring. The reaction conditions, including microwave power, temperature andtime of reaction, were screened to achieve high yield under simple operation.Results 6,7-bis(2-methoxyethoxy)quinazolin-4(3H)-one (compound 5) was successfully synthesized fromstarting material of 4,5-bis(2-methoxyethoxy)-2-nitrobenzonitrile by microwave reaction, which was finished in1 hour just by one step. The yield of heterocyclization was increased from 29.8% of commonly used three-stepscheme to 50% herein.Conclusion Microwave reaction efficiently improved synthesis of heterocyclization of 6,7-bis(2-methoxyethoxy)quinazolin-4(3H)-one into "quinazolinone in both synthetic procedure and yield. The resultsmay provide valuable reference to synthesis of other quinazolinone derivatives.en_US
dc.identifier.affiliationsCollege of Pharmacy, Jinan University, Guangzhou, Chinaen_US
dc.identifier.affiliationsGuangdong Zhongsheng Pharmaceutical Co., Ltd., Chinaen_US
dc.identifier.affiliationsInternational Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drugen_US
dc.identifier.affiliationsDevelopment of Chinese Ministry of Education, College of pharmacy, Jinan University, Guangzhou, Chinaen_US
dc.identifier.affiliationsGuangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Guangzhou, Chinaen_US
dc.identifier.affiliationsDongguan Institute of Jinan University, Dongguan 523808, Chinaen_US
dc.identifier.citationMan Jianghong, Qi Jianbin, Jiang Jie, Li Sha. Microwave Reaction Improved Heterocyclization of Quinazolinone Ring in Synthesis of Erlotinib Analogues. Journal of Pharmaceutical and Biomedical Sciences. 2020 May; 10(5): 99-105en_US
dc.identifier.issn2230-7885
dc.identifier.placeIndiaen_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/215717
dc.languageenen_US
dc.publisherLawarence Press Pvt. Ltd.en_US
dc.relation.issuenumber5en_US
dc.relation.volume10en_US
dc.source.urihttps://lawarencepress.com/ojs/index.php/JPBMS/article/view/612/pdf_296en_US
dc.subjectQuinazolinoneen_US
dc.subjectheterocyclizationen_US
dc.subjectmicrowave reaction.en_US
dc.titleMicrowave Reaction Improved Heterocyclization of Quinazolinone Ring in Synthesis of Erlotinib Analoguesen_US
dc.typeJournal Articleen_US
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