Carpenter Richard D, Deberdt Patrick B, Lam Kit S, Kurth Mark J
Department of Chemistry, University of California, Davis, Davis, California 95616, USA.
J Comb Chem. 2006 Nov-Dec;8(6):907-14. doi: 10.1021/cc060106b.
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.
我们使用碳二亚胺试剂[1,3 - 二异丙基碳二亚胺或N-(3 - 二甲氨基丙基)-N'-乙基碳二亚胺盐酸盐（EDC）]，开发了一种温和、通用的一锅法，可从市售的芳基异硫氰酸酯和邻苯二胺制备N - 2 - 芳基氨基苯并咪唑酯。经过皂化和酸化后，从起始芳基异硫氰酸酯中分离得到苯并咪唑酸，总收率为75%至88%。九种苯并咪唑酸在与市售胺进行EDC偶联后转化为由180种苯并咪唑酰胺组成的文库。美国国立综合医学科学研究所将把这些苯并咪唑酰胺分发给学术团体用于中试规模的生物医学研究。利用这些温和的条件和环境安全的试剂，我们证明了这些药学上修饰的杂环也可以在固相载体上构建。
