Pawan Kumar, Premnath Dhande, Muhammad Taufiq F. Mazlee, S. M. Yaman, Nurul Syazwani Nadirah Binti Muhammad Syafiq Chandran, M. Makhtar, Dhramveer Singh Shekhawat, S. V. Lanke, R. Kumar, Sandeep Mhetre
A simple, controlled, robust and scalable three-stage manufacturing process of Afatinib Dimaleate was assessed and optimized leading to improved yield and quality. The synthetic process involves sequence of reactions as nitro-reduction, amidation and salification. The developed and optimized route was demonstrated on 300g scale with over all isolated yield of 84% for Afatinib free base. The developed process has the capability to control not only the process related impurities but also the degradation impurities. One new impurity was identified during the process development studies and characterized as acetamide impunity, chemically known as (S)-N-(4-((3-chloro-4-fluorophenyl) amino)-7-((tetrahydrofuran-3-yl) oxy) quinazolin-6-yl) acetamide. Other impurities were identified as degradation impurities, Process impurity impurities and were labeled as 1-(4-((3-chloro-4-fluorophenyl) amino)-7-(((S)-tetrahydrofuran-3-yl) oxy) quinazoline-6-yl)-5-Hydroxypyrrolidin-2-one (hydroxy impurity), Afatinib N-Oxide impurity and N4-(3-chloro-4-fluorophenyl)-7-[[(3S)-tetrahydro-3-furanyl] oxy]-4,6-quinazolinediamine (Intermediate-1).
{"title":"A controlled, efficient and robust process for the synthesis of an epidermal growth factor receptor inhibitor: Afatinib Dimaleate","authors":"Pawan Kumar, Premnath Dhande, Muhammad Taufiq F. Mazlee, S. M. Yaman, Nurul Syazwani Nadirah Binti Muhammad Syafiq Chandran, M. Makhtar, Dhramveer Singh Shekhawat, S. V. Lanke, R. Kumar, Sandeep Mhetre","doi":"10.25082/CR.2019.01.001","DOIUrl":"https://doi.org/10.25082/CR.2019.01.001","url":null,"abstract":"A simple, controlled, robust and scalable three-stage manufacturing process of Afatinib Dimaleate was assessed and optimized leading to improved yield and quality. The synthetic process involves sequence of reactions as nitro-reduction, amidation and salification. The developed and optimized route was demonstrated on 300g scale with over all isolated yield of 84% for Afatinib free base. The developed process has the capability to control not only the process related impurities but also the degradation impurities. One new impurity was identified during the process development studies and characterized as acetamide impunity, chemically known as (S)-N-(4-((3-chloro-4-fluorophenyl) amino)-7-((tetrahydrofuran-3-yl) oxy) quinazolin-6-yl) acetamide. Other impurities were identified as degradation impurities, Process impurity impurities and were labeled as 1-(4-((3-chloro-4-fluorophenyl) amino)-7-(((S)-tetrahydrofuran-3-yl) oxy) quinazoline-6-yl)-5-Hydroxypyrrolidin-2-one (hydroxy impurity), Afatinib N-Oxide impurity and N4-(3-chloro-4-fluorophenyl)-7-[[(3S)-tetrahydro-3-furanyl] oxy]-4,6-quinazolinediamine (Intermediate-1).","PeriodicalId":66475,"journal":{"name":"化学报告(英文)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48174743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diffusion transport of Ca(NO3)2 aqueous solution in porous glass membranes","authors":"Vyacheslav N. Pak, Yulia Yu. Gavronskaya","doi":"10.25082/cr.2019.02.004","DOIUrl":"https://doi.org/10.25082/cr.2019.02.004","url":null,"abstract":"","PeriodicalId":66475,"journal":{"name":"化学报告(英文)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69216452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
With rapid developments of nano-engineering in the recent years, high-performance and multi-functional nano-materials, exhibiting new and enhanced physical and chemical properties, are introduced with innumerable conceivable applications. The recent advances in design, synthesis and characterization techniques of nano-materials have enabled the fabrication of modern nano-electro-mechanical systems (NEMS). Research breakthroughs in NEMS technology over the past decade have caused an increased interest in the analysis of structures at nano-scale, stimulated by the fact that control over these exclusive properties leads to development of concepts potentially resulting in new engineering applications......
{"title":"New trends in nano-engineering","authors":"Barretta Raffaele","doi":"10.25082/CR.2018.01.001","DOIUrl":"https://doi.org/10.25082/CR.2018.01.001","url":null,"abstract":"With rapid developments of nano-engineering in the recent years, high-performance and multi-functional nano-materials, exhibiting new and enhanced physical and chemical properties, are introduced with innumerable conceivable applications. The recent advances in design, synthesis and characterization techniques of nano-materials have enabled the fabrication of modern nano-electro-mechanical systems (NEMS). Research breakthroughs in NEMS technology over the past decade have caused an increased interest in the analysis of structures at nano-scale, stimulated by the fact that control over these exclusive properties leads to development of concepts potentially resulting in new engineering applications......","PeriodicalId":66475,"journal":{"name":"化学报告(英文)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46554393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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