BBE
Chemical Name: trans-1,2-Bis(5-amidino-2-benzimidazolyl)ethene tetrahydrochloride; (E)-2,2'-Vinylenebis(benzimidazole-5-carboxamidine) tetrahydrochloride
项目整合开发状态: Preclinical
项目研究机构: University of North Carolina (Originator)
合成路线:The synthesis of BBE was accomplished using a modified version of a published procedure,as outlined in Scheme 17960101a:Following acetylation (II) of the amine group,4-aminobenzonitrile (I) was nitrated with potassium nitrate and the acetyl group removed with boiling sulfuric acid to give the mono-nitro product (III).The nitrile was converted to the corresponding amidine in two steps via the Pinner amidine synthesis (1,2) to give 4-amino-3-nitrobenzamidine (IV).Reduction of the nitro group with 10% Pd-C in a Parr hydrogenator afforded a 60% yield (from compound I) of 3,4-diaminobenzamidine (V).The di-imidate (VII) of fumaronitrile (VI) was prepared by reacting the dinitrile in freshly distilled ethanol with dry HCl gas at 10 C.The di-imidate (VII) was reacted immediately with a 1/2 molar equivalent of 3,4-diaminobenzamidine in refluxing glacial acetic acid.The final product was isolated by trituration with ethyl acetate and filtration.BBE was purified by two recrystallizations from 4% HCl.The yield of the purified product was 15%.
📌 参考资料/链接：
参考文献标题:Diarylamidine derivatives with one or both of the aryl moieties consisting of an indole or indole-like ring.Inhibitors of arginine-specific esteroproteases
文献作者:Tidwell,R.R.; Geratz,J.D.; Dann,O.; Volz,G.; Zeh,D.; Loewe,H.
参考来源:J Med Chem 1978,21(7),613-23
📄 详细内容
合成路线:The synthesis of BBE was accomplished using a modified version of a published procedure,as outlined in Scheme 17960101a:Following acetylation (II) of the amine group,4-aminobenzonitrile (I) was nitrated with potassium nitrate and the acetyl group removed with boiling sulfuric acid to give the mono-nitro product (III).The nitrile was converted to the corresponding amidine in two steps via the Pinner amidine synthesis (1,2) to give 4-amino-3-nitrobenzamidine (IV).Reduction of the nitro group with 10% Pd-C in a Parr hydrogenator afforded a 60% yield (from compound I) of 3,4-diaminobenzamidine (V).The di-imidate (VII) of fumaronitrile (VI) was prepared by reacting the dinitrile in freshly distilled ethanol with dry HCl gas at 10 C.The di-imidate (VII) was reacted immediately with a 1/2 molar equivalent of 3,4-diaminobenzamidine in refluxing glacial acetic acid.The final product was isolated by trituration with ethyl acetate and filtration.BBE was purified by two recrystallizations from 4% HCl.The yield of the purified product was 15%.
参考文献标题:BBE
文献作者:Tidwell,R.R.; Geratz,J.D.
参考来源:Drugs Fut 1992,17(5),371