【药物名称】CRX-395
化学结构式(Chemical Structure):
参考文献No.61021
标题:Cytotoxic agents
作者:McGee, D.P.C.; Saunders, O.L.; Martichonok, V.; Wu, G.; Ng, H.P.; Li, Z.; Yarranton, G.T. (Medarex, Inc.)
来源:US 2003050331; WO 0296910
合成路线图解说明:

5-Nitrobenzofuran-2-carboxylic acid (I) is coupled to 4-nitrophenol (II) in the presence of EDC to produce the p-nitrophenyl ester (III). Subsequent acylation of the duocarmycin derivative (IV) with active ester (III) leads to amide (V). Cyclopropane ring opening in (V) with HCl in DMF furnishes the chloromethyl derivative (VI). The nitro group of (VI) is then reduced by catalytic hydrogenation, yielding amine (VII). Acylation of (VII) with 7-nitroindole-2-carboxylic acid (VIII) affords the corresponding amide (IX)

合成路线图解说明:

The phenolic hydroxyl group of (IX) is acylated by 4-nitrophenyl chloroformate (X), producing carbonate (XI). Then, displacement of the 4-nitrophenoxy group of (XI) with N-methylpiperazine (XII) yields carbamate (XIII). Finally, nitro group reduction in (XIII) gives rise to the title compound

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