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 involvessequence of reactions ...
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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 300 g 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 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).
一、引言学界一向有关于国家能力跨学科研究的传统,在政治科学和政治社会学领域尤甚(Cingolani,2013,2018)。近年来,这一概念更多转向国家能力的行政维度,即行政能力,并被广泛运用于公共行政和政策研究中(El-Taliawi and van der Wal,20...
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一、引言学界一向有关于国家能力跨学科研究的传统,在政治科学和政治社会学领域尤甚(Cingolani,2013,2018)。近年来,这一概念更多转向国家能力的行政维度,即行政能力,并被广泛运用于公共行政和政策研究中(El-Taliawi and van der Wal,2019)。就其对经济增长、工业发展、政策实施和国家整体发展的必要性而言,行政能力的实践重要性尤为显著(Cingolani,2013;El-Taliawi and van der Wal,2019)。
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