Synlett 2004(9): 1607-1609  
DOI: 10.1055/s-2004-829077
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Solid-Phase Approach to Fluorobenzimidazoles and Fluoro-2-hydroxyquinoxalines Using ’One-Bead-Two-Compound’ Method

Ya-Fei Ji*a, Xian-Dao Panb, Xian-Yong Weic
a Department of Pharmacy Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China
Fax: +86(21)54938392; e-Mail: ji_yafei@yahoo.com.cn;
b Institute of Meteria Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Beijing 100050, P. R. China
c School of Chemical Engineering, China University of Mining and Technology, Xuzhou 221008, P. R. China
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Publikationsverlauf

Received 19 February 2004
Publikationsdatum:
29. Juni 2004 (online)

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Abstract

A solid-phase approach to fluorobenzimidazoles 6a and fluoro-2-hydroxyquinoxalines 6b has been achieved by a new strategy of ‘one-bead-two-compound’. The precursor, 6-nitro-2,3,4,5-tetrafluorobenzoic acid, was tagged to Rink amide MBHA resin via an α-amino acid linker. The first nucleophilic substitution generated two regioisomers in which the second active fluorine atom underwent a subsequent nucleophilic substitution with a primary amine. The reduction of the aryl nitro groups with SnCl2⟨2H2O/NMM and the formation of a five-membered ring with aldehydes afforded 4b and 5a. Fluorobenzimidazoles 6a were directly furnished by cleavage using TFA, therewith the stable six-membered ring 6b was produced by concomitant intramolecular cyclization and thermal dehydrogenation. In addition to introduction of fluorine into the heterocycles, two scaffolds could be simultaneously synthesized with this method.