【药物名称】
化学结构式(Chemical Structure):
参考文献No.37192
标题:Benzimidazole derivs.
作者:Chamberlain, S.D.; Koszalka, G.W.; Chan, J.H.; Townsend, L.B.; Tidwell, J.H.; Drach, J.C.; Freeman, G.A. (Glaxo Wellcome plc; University of Michigan)
来源:EP 0970100; WO 9835977
合成路线图解说明:

Fluorination of 4,5-dichloro-2-nitroaniline (I) with 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoborate) (II) gave fluoroaniline (III). The nitro group of (III) was then reduced by hydrogenation over Raney-Ni to afford phenylenediamine (IV). This was cyclized with isopropyl isothiocyanate in the presence of 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate as the desulfurizing agent to yield benzimidazole (V). Coupling with 1,2,3-tri-O-acetyl-5-deoxy-D-ribofuranose (VI) using trimethylsilyl triflate and N,O-bis(trimethylsilyl)acetamide produced a mixture of regioisomeric ribofuranosyl benzimidazoles (VII) and (VIII), which were separated by column chromatography. Finally, deprotection of the acetate esters from the major isomer (VII) with Na2CO3 provided the title compound.

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