Carbodiimide-based benzimidazole library method.
Using carbodiimide reagents [1,3-diisopropylcarbodiimide or N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)], we have developed a mild, generalized, one-pot method that delivers N-2-arylaminobenzimidazole esters from commercially available aryl isothiocyanates and o-phenylenediamines. Following saponification and acidifying, the benzimidazole acids were isolated in overall yields ranging from 75 to 88% from the starting aryl isothiocyanates. Nine benzimidazole acids were converted into a library consisting of 180 benzimidazole amides following EDC coupling with commercially available amines. The National Institute of General Medical Science will dispense these benzimidazole amides to academia groups for pilot scale biomedical studies. Using these mild conditions and environmentally safe reagents, we demonstrated that these pharmaceutically ornate heterocycles can also be constructed on solid support.
Carpenter
Richard D
RD
Department of Chemistry, University of California, Davis, Davis, California 95616, USA.
Deberdt
Patrick B
PB
Lam
Kit S
KS
Kurth
Mark J
MJ
D000577:Amides / Q000737:chemistry; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D002234:Carbodiimides / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015394:Molecular Structure; D013237:Stereoisomerism
D000577:Amides; D001562:Benzimidazoles; D002234:Carbodiimides