Solution-Phase and Solid-Phase Synthesis of 1-Pyrazol-3-ylbenzimidazoles

Jaime Portilla; Jairo Quiroga; Rodrigo Abonía; Braulio Insuasty; Manuel Nogueras; Justo Cobo; Ernesto G. Mata

doi:10.1055/s-2008-1032030

PAPER

Solution-Phase and Solid-Phase Synthesis of 1-Pyrazol-3-ylbenzimidazoles

Jaime Portilla^a, Jairo Quiroga*^a, Rodrigo Abonía^a, Braulio Insuasty^a, Manuel Nogueras^b, Justo Cobo^b, Ernesto G. Mata*^c
^a Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, A. A. 25360, Cali, Colombia
e-Mail: jaiquir@gmail.com;
^b Departamento de Química Inorgánica y Orgánica, Universidad de Jaén, 23071 Jaén, Spain
^c Instituto de Química Orgánica de Síntesis (CONICET - UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina
Fax: +54(341)4370477; e-Mail: mata@iquios.gov.ar;

Abstract

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Abstract

The facile solution and solid-phase synthesis of 1-pyrazol-3-ylbenzimidazoles from 4-fluoro-3-nitrobenzoate derivatives and 5(3)-amino-3(5)-subtituted-1H-pyrazoles is reported. The key step is the unexpected nucleophilic aromatic displacement of the activated fluorine by the exocyclic amino group of the pyrazole ring leading to 4-pyrazolylamino-3-nitrobenzoate derivatives, which are easily converted into the corresponding 1-pyrazol-3-ylbenzimidazoles in very high isolated yield. These novel methodologies would be very useful for the generation of libraries of diverse 1-heteroaryl derivatives of benzimidazoles.

Key words

solid-phase synthesis - combinatorial chemistry - heterocycles - benzimidazoles - pyrazoles

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References

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