FR-143187

Chemical Name: 7-Methyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)pyrrol-1-yl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine hydrochloride
项目整合开发状态: Preclinical
项目研究机构: Fujisawa (Originator)
合成路线: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.