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Synthesis 2012(4): 610-618  
DOI: 10.1055/s-0031-1290068
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Highly Efficient and Broad-Scope Protocol for the Preparation of 7-Substituted 6-Halopurines via N 9-Boc-Protected 7,8-Dihydropurines

Vladislav Kotek, Tomáš Tobrman, Dalimil Dvořák*
Department of Organic Chemistry, Institute of Chemical Technology, Prague, Technická 5, 2166 28 Prague 6, Czech Republic
Fax: +42(224)354288; e-Mail: dvorakd@vscht.cz;
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Publication History

Received 26 October 2011
Publication Date:
03 January 2012 (online)

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Abstract

9-Boc-6-chloropurine, which can be obtained in high yield, is nearly quantitatively reduced with the THF˙BH3 complex. The obtained 9-Boc-7,8-dihydropurine derivative is more stable compared to the corresponding 9-tritylpurine and can be smoothly N7-alkylated, acylated, or it can serve as an N-nucleophile in conjugate additions. Deprotection with trifluoroacetic acid followed by MnO2 oxidation affords the N7-substituted purines in high yields. The whole sequence of alkylation, deprotection, and oxidation can be done with crude intermediates using chromatography only for the purification of the final N7-substituted purine.

Key words

alkylation - acylation - Michael addition - nucleobases - reduction

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