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Synthesis 2012(6): 953-965  
DOI: 10.1055/s-0031-1289694
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A General Regioselective Approach to 2,4-Disubstituted Pyrimidin-5-yl C-2-Deoxyribonucleosides

Tomáš Kubelkaa, Lenka Slavětínskáa, Michal Hocek*a,b
a Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
b Department of Organic and Nuclear Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843 Prague 2, Czech Republic
Fax: +420(2)20183559; e-Mail: hocek@uochb.cas.cz;
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Publikationsverlauf

Received 9 December 2011
Publikationsdatum:
06. Februar 2012 (online)

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Abstract

A new modular synthesis of diverse 2,4-disubstituted pyrimidin-5-yl C-2′-deoxyribonucleosides by sequential regioselective reactions of 2,6-dichloropyrimidin-5-yl C-nucleoside was developed. The intermediate was prepared by the Heck coupling of 2,6-dichloro-5-iodopyrimidine with glycal followed by desilylation and reduction. Its mild nucleophilic substitutions or cross-coupling reactions proceeded regioselectively at position 4, while at elevated temperatures or with excess reagent, a double substitution occurred. The 2-chloro-4-substituted intermediates underwent another substitution or coupling to afford a two-dimensional library of diverse 2,4-disubstituted pyrimidin-5-yl C-2-deoxyribonucleotides.

Key words

nucleosides - cross-coupling - Heck reaction - nucleophilic aromatic substitution - regioselectivity

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