合成路线1

Two new syntheses of labeled azamianserin have been described: 1) [13C]-Labeled: The reaction of 2-chloropyridine-3-carbonitrile (I) with glycine ethyl ester (II) by means of Na2CO3 in DMSO gives N-(3-cyanopyridin-2-yl)glycine ethyl ester (III), which by reaction with methylamine in toluene is converted into the corresponding amide (IV). The treatment of (IV) with sodium hypophosphite and RaNi in water-acetic acid-pyridine affords N-(3-formylpyridin-2-yl)glycine methylamide (V), which is reduced with NaBH4 in methanol to the corresponding alcohol (VI). Further reduction of (VI) with LiAlH4 in refluxing dioxane gives 2-[2-(methylamino)ethylamino]-3-pyridinemethanol (VII), which is condensed with [13C]-labeled alpha-bromoacetophenone (VIII) [prepared from labeled benzene (IX) submitted to a Friedel-Crafts condensation with AlCl3 and acetic anhydride to acetophenone (X) and bromination with Br2 in ether] by means of triethylamine in dioxane to afford the substituted acetophenone (XI). The cyclization of (XI) by heating at 120 C yields the tricyclic compound (XII), which is reduced with LiAlH4 - AlCl3 in ethyl ether to give 2-(4-methyl-2-phenylpiperazin-1-yl)pyridine-3-methanol (XIII). Finally, this compound is cyclized in hot H2SO4.