【药物名称】AVE-0991
化学结构式(Chemical Structure):
参考文献No.45796
标题:1-(p-Thienylbenzyl)-imidazoles as angiotensin-(1-7) receptor agonists, method for the production and the utilization thereof and pharmaceutical preparations containing said cpds.
作者:Wiemer, G.; Heitsch, H. (Aventis Pharma Deutschland GmbH)
来源:EP 1185527; JP 2002544130; US 6235766; US 6429222; WO 0068226
合成路线图解说明:

4-Chloro-5-formyl-2-phenylimidazole (I) is alkylated with 4-bromobenzyl bromide (II) in the presence of K2CO3 in DMF to produce the N-bromobenzyl imidazole (III). Subsequent Suzuki coupling between aryl bromide (III) and 5-isobutyl-2-[(N-tert-butyl)sulfonamido]thiophene-3-boronic acid (IV) affords the thienylphenyl derivative (V). The N-tert-butyl group is then removed by treatment with trifluoroacetic acid in the presence of anisole, yielding sulfonamide (VI). Displacement of the chloro substituent of (VI) with MeOH/NaOH furnishes the 4-methoxy imidazole (VII). Finally, condensation of sulfonamide (VII) with ethyl isocyanate gives rise to the target N-sulfonyl urea compound.

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