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Synthesis 2011(15): 2431-2436  
DOI: 10.1055/s-0030-1260080
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Highly Regioselective Palladium-Catalyzed C2-Amination of 2,4-Dichloropyridines: Scope and Limitations

Christian Delvare, Patrice Koza, Rémy Morgentin*
AstraZeneca, Centre de Recherches, Parc industriel Pompelle B.P.1050, 51689 Reims cedex 2, France
Fax: +33(3)26616842; e-Mail: remy.morgentin@astrazeneca.com;
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Publication History

Received 17 March 2011
Publication Date:
21 June 2011 (online)

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Abstract

The use of palladium(0) enables a highly regioselective C-2 amination of 4,6-dichloronicotinonitrile. Coupling with aminoarenes that are N-acetyl-masked to limit cross-coupling overreaction, leads to 4-chloro-6-anilino nicotinonitrile compounds after deprotection in situ. The scope of these original conditions was evaluated.

Key words

regioselectivity - palladium - amination - pyridines - cross-coupling

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5

Regioselectivity was confirmed by NMR studies on intermediates and final compounds made by two different methods.4

7

Patrice Koza developed a robust method (0.2% attrition) for the rapid purification of a wide range of compounds by preparative HPLC/MS. Koza, P.; unpublished results.