Using a Johnson‐Claisen Rearrangement Strategy to Construct Azaindoles – A Streamlined and Concise Route for the Commercial Process of Fevipiprant
| العنوان: | Using a Johnson‐Claisen Rearrangement Strategy to Construct Azaindoles – A Streamlined and Concise Route for the Commercial Process of Fevipiprant |
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| المؤلفون: | Fei Zhongbo, Darija Dedic, Philipp Lustenberger, Ueli Rüegger, Christian Mathes, Matthias Napp, Kurt Königsberger, Bernard Riss, Thierry Schlama, Glen Dempsey, Carolien den Reijer, Lukas Hueber |
| المصدر: | European Journal of Organic Chemistry. 2021:4490-4494 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | chemistry.chemical_classification, Allene, Organic Chemistry, Sonogashira coupling, Fevipiprant, Reductive amination, Aldehyde, Combinatorial chemistry, Claisen rearrangement, chemistry.chemical_compound, chemistry, Side chain, Hydroamination, Physical and Theoretical Chemistry |
| الوصف: | A novel and concise synthesis towards DP2 receptor antagonist Fevipiprant (NVS-QAW039) was developed. The initial research route was suffering from lengthy access to the functionalized 7-aza-indole core followed by a low selective N(1)-alkylation with the benzyl side chain. These limitations were overcome by introducing the side chain early via reductive amination between the functionalized aldehyde and 2-amino-3-bromopyridine. Sonogashira coupling with prop-2-yn-1-ol introduces the 3 missing carbon atoms to build the 7-aza-indole core and sets the stage for the innovative Johnson-Claisen key step. Reaction of the advanced propargylic alcohol derivative with trimethyl orthoacetate leads to a reactive allene intermediate that spontaneously and selectively cyclizes to the 7-aza-indole QAW039-methly ester. QAW039 is isolated after ester saponification. Selectivity, yield, and ecological footprint of the new synthesis were significantly improved, and scalability was demonstrated. |
| تدمد: | 1099-0690 1434-193X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::39251ab8b96d07356ed454b446027b76 https://doi.org/10.1002/ejoc.202100686 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........39251ab8b96d07356ed454b446027b76 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10990690 1434193X |
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