【药物名称】FR-143187
化学结构式(Chemical Structure):
参考文献No.567275
标题:Pilot scale synthesis of a novel nonpeptide angiotensin II receptor antagonist
作者:Zanka, A.; et al.
来源:Org Process Res Dev 1998,2(4),230
合成路线图解说明:

The condensation of ethyl 4-aminobenzoate (I) with 2,5-dimethoxytetrahydrofuran (II) in refluxing acetic acid/toluene gives ethyl 4-(1-pyrrolyl)benzoate (III), which by a Mannich reaction with formaldehyde and dimethylamine, followed by quaternization with methyl iodide in N,N'-dimethylimidazolidininone (DMI) yields the trimethylammonium salt (IV). The reduction of (IV) with borane/pyridine complex in DMI affords ethyl 4-(2-methyl-1-pyrrolyl)benzoate (V), which is treated with chlorosulfonyl isocyanate in heptane/toluene affording ethyl 4-(2-cyano-5-methyl-1-pyrrolyl)benzoate (VI). The reduction of (VI) with NaBH4 in methanol gives the benzyl alcohol (VII), which is treated with Ms-Cl and triethylamine to yield the mesylate (VIII). The condensation of (VIII) with N-(4-methyl-3-nitropyridin-2-yl)butyramide (IX) by means of NaOH and K2CO3 affords the disubstituted amide (X), which is cyclized by reduction of its nitro group with Fe and AcOH giving the imidazo[4,5-b]pyridine (XI). Finally, this compound is condensed with sodium azide and triethylamine in hot DMI in order to form the tetrazole ring of the target compound, which is salified with HCl in isopropanol/water.

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