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Synthesis 2004(16): 2625-2628  
DOI: 10.1055/s-2004-831227
PAPER
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of 4-(3-Fluoro-5-{[4-(2-methyl-1H-imidazol-1-yl)benzyl]oxy}phenyl)tetrahydro-2H-pyran-4-carboxamide, a Novel 5-Lipoxygenase Inhibitor

Takashi Mano*, Rodney W. Stevens, Kazunari Nakao, Yoshiyuki Okumura, Kiyoshi Kawamura, Akemi Ando, Yoko Matsuoka
Pfizer Global Research & Development, Nagoya Laboratories, 5-2 Taketoyo, Aichi 470-2393, Japan
Fax: +81(569)74 4748; e-Mail: Takashi.Mano@pfizer.com;
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Publication History

Received 19 April 2004
Publication Date:
22 September 2004 (online)

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Abstract

An efficient synthesis of 1, a novel orally active 5-lipoxygenase inhibitor, was developed. Key features of the modified synthetic route include facile construction of the benzyl phenyl ether moiety by nucleophilic aromatic substitution and THP ring by cyclization, and base-promoted hydrolysis of the nitrile group to carboxamide. The improved three-step synthesis provides 25 g of 1 for pre-clinical toxicology studies in a total yield of 59%.

Key words

amides - cyclizations - drugs - nitriles - nucleophilic aromatic substitutions

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