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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">pharmjournal</journal-id><journal-title-group><journal-title xml:lang="ru">Разработка и регистрация лекарственных средств</journal-title><trans-title-group xml:lang="en"><trans-title>Drug development &amp; registration</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2305-2066</issn><issn pub-type="epub">2658-5049</issn><publisher><publisher-name>LLC «CPHA»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.33380/2305-2066-2020-9-1-13-17</article-id><article-id custom-type="elpub" pub-id-type="custom">pharmjournal-758</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ПОИСК И РАЗРАБОТКА НОВЫХ ЛЕКАРСТВЕННЫХ СРЕДСТВ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>RESEARCH AND DEVELOPMENT OF NEW DRUG PRODUCTS</subject></subj-group></article-categories><title-group><article-title>Новые подходы к совершенствованию микрореакторного синтеза бендамустина</article-title><trans-title-group xml:lang="en"><trans-title>New Approaches to Improving Bendamustine Microractor Synthesis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Молдавский</surname><given-names>А. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Moldavsky</surname><given-names>A. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Молдавский Александр Л.</p><p>197376, Санкт-Петербург, ул. Проф. Попова, д. 14, лит. А</p></bio><bio xml:lang="en"><p>Alexander L. Moldavsky</p><p>14A, Prof. Popov str., Saint-Petersburg, 197376</p></bio><email xlink:type="simple">amoldavski@pharmstd.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Юраков</surname><given-names>А. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Yurakov</surname><given-names>A. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197376, Санкт-Петербург, ул. Проф. Попова, д. 14, лит. А</p></bio><bio xml:lang="en"><p>Andrei M. Yurakov</p><p>14A, Prof. Popov str., Saint-Petersburg, 197376</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лалаев</surname><given-names>Б. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Lalaev</surname><given-names>B. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197376, Санкт-Петербург, ул. Проф. Попова, д. 14, лит. А</p></bio><bio xml:lang="en"><p>Boris Yu. Lalaev</p><p>14A, Prof. Popov str., Saint-Petersburg, 197376</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Фридман</surname><given-names>И. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Fridman</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197376, Санкт-Петербург, ул. Проф. Попова, д. 14, лит. А</p></bio><bio xml:lang="en"><p>Ilya A. Fridman</p><p>14A, Prof. Popov str., Saint-Petersburg, 197376</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Министерства здравоохранения Российской Федерации</institution></aff><aff xml:lang="en"><institution>Saint-Petersburg State Chemical-Pharmaceutical University</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>26</day><month>02</month><year>2020</year></pub-date><volume>9</volume><issue>1</issue><fpage>13</fpage><lpage>17</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Молдавский А.Л., Юраков А.М., Лалаев Б.Ю., Фридман И.А., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Молдавский А.Л., Юраков А.М., Лалаев Б.Ю., Фридман И.А.</copyright-holder><copyright-holder xml:lang="en">Moldavsky A.L., Yurakov A.M., Lalaev B.Y., Fridman I.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.pharmjournal.ru/jour/article/view/758">https://www.pharmjournal.ru/jour/article/view/758</self-uri><abstract><sec><title>Введение</title><p>Введение. Реакция хлорирования в синтезе фармацевтической субстанции бендамустина гидрохлорида является сложным технологическим процессом. Наличие побочных реакций и образующиеся при этом примеси затрудняют процессы масштабирования [1–4].</p></sec><sec><title>Цель</title><p>Цель. Совершенствование процесса хлорирования в микрореактором синтезе бендамустина для повышения производительности технологии.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Проведена серия экспериментов по совершенствованию технологии хлорирования в синтезе бендамустина гидрохлорида в проточном микрореакторе с различными концентрациями реагентов.</p></sec><sec><title>Результаты и обсуждение</title><p>Результаты и обсуждение. Повышение концентрации исходных реагентов в реакционной массе позволило увеличить производительность технологии получения этилового эфира бендамустина (этиловый эфир 4-{5-[бис(2-гидроксоэтил)амино]-1-метилбензимидазол-2-ил}бутановой кислоты). Оптимизированы условия реакции хлорирования в синтезе бендамустина гидрохлорида, проанализированы возможные пути дальнейшего увеличения производительности. Изучено влияние изменения концентрации реагентов в исходных растворах и скоростей потоков растворов реагентов на конечный продукт реакции.</p></sec><sec><title>Заключение</title><p>Заключение. Определены оптимальные концентрации реагентов в исходных растворах, позволяющие достичь производительности проточного микрореактора объемом 137 мл, которая эквивалентна производительности емкостного реактора объемом 100 л.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. The chlorination reaction in the synthesis of the substance of bendamustine hydrochloride is a complex process. The presence of active adverse reactions makes scaling difficult.</p></sec><sec><title>Aim</title><p>Aim. Improving the performance of the technology for producing bendamustine ethyl ester in a flow microreactor.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. A series of experiments was carried out to carry out the chlorination stage in the synthesis of bendamustine hydrochloride in a flow microreactor with various concentrations in the initial reagent solutions.</p></sec><sec><title>Results and discussion</title><p>Results and discussion. Experimental work was carried out to increase the productivity of the technology for the preparation of bendamustine ethyl ester (4-{[5-[bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl}butanoic acid ethyl ester) by increasing the concentration of the starting reagents in the reaction mass. The conditions for conducting the chlorination reaction in the synthesis of bendamustine hydrochloride have been optimized, and possible ways to further increase productivity have been analyzed. The effect of changes in the concentration of reagents in the initial solutions and flow rates of reagent solutions on the final reaction product was studied.</p></sec><sec><title>Conclusion</title><p>Conclusion. The optimal concentrations of reagents in the initial solutions were selected, allowing to increase the productivity of the flow microreactor with a volume of 137 mL to an equivalent level of a 100 liter capacitive reactor.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>бендамустин</kwd><kwd>бендамустина гидрохлорид</kwd><kwd>хлорирование</kwd><kwd>проточный микрореактор</kwd></kwd-group><kwd-group xml:lang="en"><kwd>bendamustine</kwd><kwd>bendamustine hydrochloride</kwd><kwd>chlorination</kwd><kwd>flow microreactor</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Krebs Dietrich, Ozegowski Werner, Gutsche Walter, Heinecke Horst, Jungstand Walter, Knoell Hans, Wiankge Heinrich. Verfahren Zur Herstellung Von 1-stellung Substituierten [5-bis-(chloräthyl)amino-benzimidazolyl-(2)]-alkancarbonsäuren. 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