A highly efficient synthesis route for the rapid generation of 1,2,5,6-tetrasubstituted benzimidazoles

Synlett

Volumn , Issue 10, 2008, Pages 1467-1470

  Duschmalé, Jörg J ^a   Woltering, Thomas J ^a   Bleicher, Konrad H ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Benzimidazoles; Medicinal chemistry; Nucleophilic aromatic substitution; Palladium coupling; Parallel synthesis

Indexed keywords

5 CHLORO 4 IODO 2 NITROANILINE; ANILINE DERIVATIVE; BENZIMIDAZOLE DERIVATIVE; CHLORINE DERIVATIVE; IODINE DERIVATIVE; NITRO DERIVATIVE;

ALKYLATION; ARTICLE; CATALYST; CRYSTALLIZATION; QUANTUM YIELD; REACTION ANALYSIS; SUZUKI REACTION; SYNTHESIS;

EID: 46449101723     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2008-1077791     Document Type: Article

References (12)

1. Bleicher, K. H.; Nettekoven, M.; Peters, J.-U.; Wyler, R. Chimia 2004, 58, 588.
2. Bleicher, K. H.; Boehm, H.-J.; Mueller, K.; Alanine, A. Nature Rev. Drug Discov. 2003, 2, 396.
3. Imidazole and Benzimidazole Synthesis; Ross Grimmett, M., Ed.; Academic Press: London, 1997.
4. Wilson, J. G.; Hunt, F. C. Austr. J. Chem. 1983, 36, 2317.
5. (a) Adam, G.; Alanine, A.; Goetschi, E.; Mutel, V.; Woltering, T. J. WO 2001029011,2001; Chem. Abstr. 2001, 134, 311234.
6. (b) Adam, G.; Goetschi, E.; Mutel, V.; Wichmann, J.; Woltering, T. J. WO 2002083652, 2002; Chem. Abstr. 2002, 137, 325447.
7. 2 or used directly in the following step.
8. 2O and dried under vacuum. The residue could be purified by crystallization from MeOH or used directly in the following step.
9. 2O. The residue could be purified by crystallization from MeOH or MeCN or used directly in the following step.
10. 2 or used directly in the following step.
11. 3. The crude product was not further purified.
12. General Procedure for Cyclization Reactions The crude products from the previous step were treated with neat TFA and stirred at r.t. for 2 h. Depending on the residues introduced, partial cyclization to the corresponding benzimidazole was observed. Full conversion was obtained after evaporation of the TFA, dissolution of the mixture in AcOH and heating to 80 °C overnight. All final library products were isolated by preparative HPLC and characterized via LC-MS.