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Synthesis 2009(10): 1715-1719  
DOI: 10.1055/s-0028-1088057
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Tandem CH-Activation-Imine-Formation Reaction: A New Route to Imidazo[2,1-a]phthalazines

Alexander Heim-Riether*, Kevin R. Gipson
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
Fax: +1(203)7916072; e-Mail: alexander.heim-riether@boehringer-ingelheim.com;
Further Information

Publication History

Received 14 December 2008
Publication Date:
20 April 2009 (online)

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Abstract

A general and efficient synthesis of imidazo[2,1-a]phthalazines by palladium- and copper-mediated coupling of N-aminoimidazoles with 2-haloaryl aldehydes with concurrent imine formation is described. This new synthesis of the imidazo[2,1-a]phthalazine ring system allows for facile introduction of different substituents around the entire core.

Key words

imidazo[2,1-a]phthalazine - imine formation - CH activation - N-aminoimidazoles - 2-bromoaryl aldehydes

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6

No imine formation was observed under standard coupling conditions without one of the two metals (Pd, Cu) present.

10

Starting 1-aminoimidazoles, except commercially available benzimidazol-1-ylamine, were prepared according to reference 3.