An Efficient Synthesis of the Anti-asthmatic Agent T-440: A Selective N-Alkylation of 2-Pyridone
| Autor: | Tooru Kuroda, Kazuhiko Kondo, Tatsuzo Ukita, Masakatsu Sugahara, Hideshi Shimadzu, Yasunori Moritani |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular chemistry.chemical_classification Alkylation Pyridones Iodide Ab initio General Chemistry General Medicine Naphthalenes Medicinal chemistry law.invention 2-Pyridone chemistry.chemical_compound chemistry law Yield (chemistry) Drug Discovery Moiety Anti-Asthmatic Agents Crystallization Derivative (chemistry) |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 48:589-591 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.48.589 |
| Popis: | 6,7-Diethoxy-1-[1-(2-methoxyethyl)-2-oxo-1,2-dihydropyridin- 4-yl]naphthalene-2,3-dimethanol [T-440, (1)] is a potential anti-asthmatic agent based on selective phosphodiesterase 4 inhibition. It was necessary for the further evaluation of 1 to develop an efficient synthetic route for 1, especially the construction of the 1-(2-methoxyethyl)-2-pyridone moiety. We examined an N-selective alkylation of pyridone derivative (2) in basic media. 2-Methoxyethylation of 2 with 2-methoxyethyl iodide utilizing LiH as the base gave predominantly an N-alkyl pyridone derivative (3a) in 82% yield (N/O-alkylation=92/8), which is compatible with an ab initio calculation of transition-state structures for the methylation of 2-pyridone. Single crystallization of a crude mixture of 3a and 4a furnished pure 3a, which is a key synthetic intermediate of 1. |
| Databáze: | OpenAIRE |
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