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Synthesis 2010(1): 63-66  
DOI: 10.1055/s-0029-1217084
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Pyridines Substituted with Five Different Elements

Fredrik von Kieseritzky*, Johan Lindström
Discovery Research CNS & Pain Control, Medicinal Chemistry, AstraZeneca R & D Södertälje, 151 85 Södertälje, Sweden
Fax: +46(8)55328892; e-Mail: fredrik.vonkieseritzky@astrazeneca.com;
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Publikationsverlauf

Received 22 June 2009
Publikationsdatum:
22. Oktober 2009 (online)

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Abstract

By stepwise and regioselective installation of functional groups, we have synthesized and characterized two pyridines, 3-fluoro-5-iodo-2-(methylthio)-6-(trimethylsilyl)isonicotinonitrile and 3-fluoro-5-iodo-2-methoxy-6-(trimethylsilyl)isonicotinonitrile, substituted with five different elements, not including hydrogen, using known and newly developed methods. Novel methodology for dehalocyanation of iodopyridines and rapid, high-yielding microwave-assisted acidic hydrolysis of 2-fluoropyridines to their corresponding 2-pyridones are disclosed.

Key words

pyridines - regioselectivity - lithiation - hydrolyses - nucleophilic aromatic substitutions

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1

For example: the proton pump-inhibitor omeprazole, the hypnotic agent zopiclone, the antidepressant mirtazepine, the anti-inflammatory agent sulfasalazine, and the antiarrhythmic agent disopyramid.

2

For example: nicotine from tobacco, ricinine from castor bean, pyridoxine (vitamin B6) from milk or meat products, and epibatidine from the skin of a neotropical poisonous frog, Epipedobates tricolor.