- HETEROAROMATIC DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF
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Provided herein are novel heteroaromatic derivatives, or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a prodrug, a pharmaceutically acceptable salt or a prodrug thereof, and pharmaceutical compositions containing such compounds. Also provided herein are uses of such compounds or pharmaceutical compositions thereof in the manufacture of a medicament for treating respiratory diseases, especially chronic obstructive pulmonary disease (COPD).
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Paragraph 00433
(2015/11/10)
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- Synthesis of an impurity in crude roflumilast
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A simple synthetic method has been developed for the synthesis of 3,4-bis(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl) benzamide (an impurity in crude roflumilast) from 3,4-dihydroxybenzaldehyde via alkylation, oxidation, chlorination and acylation reactions. Acetonitrile was used as the solvent in all the three steps for convenient recovery. The oxidation of 3,4-bis(cyclopropylmethoxy)benzaldehyde (purity, 86.2%) by sodium chlorite afforded the corresponding acid with purity of 99.2%. Finally, N-acylation of 3,5-dichloropyridin-4-amine yielded 3,4-bis(cyclopropylmethoxy)-N-(3,5- dichloropyridin-4-yl) benzamide. Without column chromatography, the overall yield of the target compound was about 70%.
- Zhang, Hankang,Lin, Yan,Li, Yan,Dong, Kai,Chen, Ligong,Wang, Donghua
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p. 507 - 509
(2014/11/08)
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