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Synthesis 2010(12): 2017-2022  
DOI: 10.1055/s-0029-1218758
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioconservative Synthesis of Polysubstituted Pyrimido[4,5-b]azepines

Britta Gerig, Ulrich Girreser, Martin Schütt, Dieter Heber*
Christian Albrechts University of Kiel, 24118 Kiel, Germany
e-Mail: dheber@pharmazie.uni-kiel.de;
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Publication History

Received 3 January 2010
Publication Date:
28 April 2010 (online)

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Abstract

A three-step enantioconservative protocol was developed for the synthesis of polysubstituted pyrimido[4,5-b]azepines. First, 1,3-dimethyl-6-[N-(2-alkoxycarbonylalkyl)amino]uracils were synthesized by nucleophilic substitution of 6-chloro-1,3-di­methyluracil with amino acids. Subsequent acylation of the uracils by a mixture of acetic anhydride and cyanoacetic acid gave the corresponding 5-cyanoacetylated pyrimidines. In the final step, the pyrimidines were subjected to Dieckmann cyclization with a sodium alcoholate in the corresponding alcohol to afford the corresponding pyrimido[4,5-b]azepines. By using uracils of N-monosubstituted amino acids, cyclization was combined with ring opening of the pyrimidine ring system to afford polysubstituted azepines.

Key words

ring closure - heterocycles - stereoselective synthesis - pyrimidoazepines - nucleophilic substitutions

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