Розробка багатостадійної технології промислового синтезу АФІ левосимендану та енантіомерного розділення проміжних продуктів
A method for obtaining Levosimendan suitable for industrial application has been developed. Two literature routes for the synthesis have been evaluated. It has been found that the use of enantiopure (R)-2-chloropropionyl chloride in the initial step is ineffective due to racemization at the stage of...
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| Datum: | 2025 |
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| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | English |
| Veröffentlicht: |
National University of Pharmacy
2025
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| Online Zugang: | https://ophcj.nuph.edu.ua/article/view/322447 |
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| Назва журналу: | Journal of Organic and Pharmaceutical Chemistry |
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Journal of Organic and Pharmaceutical Chemistry| Zusammenfassung: | A method for obtaining Levosimendan suitable for industrial application has been developed. Two literature routes for the synthesis have been evaluated. It has been found that the use of enantiopure (R)-2-chloropropionyl chloride in the initial step is ineffective due to racemization at the stage of the synthesis based on the malonic ester. Instead, a reported method based on the synthesis of the Levosimendan precursor, 6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (1), from racemic 2-bromopropionyl bromide has been modified to allow for scale-up and adaptation to industrial processes. A practical resolution method has been developed to isolate the (R)-enantiomer of amine 1 from the racemic mixture with a high enantiomeric purity (the content of (R)-enantiomer is up to 99%). It has been shown that (R)-1 can be converted to Levosimendan in a high yield without the stereochemical purity loss at the chiral center. |
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