合成路线1

A new synthesis of centperazine has been reported: The cyclization of N,N'-dibenzylethylenediamine (I) with 2,3-dibromopropionitrile (II) by means of triethylamine in refluxing toluene gives 2-(1,4-dibenzylpiperazin-2-yl)acetonitrile (III), which is reduced with H2 over RaNi in methanol to yield the corresponding ethylamine (IV). Acylation of (IV) with ethyl chloroformate (V) and triethylamine in dichloromethane affords the corresponding carbamate (VI), which is debenzylated by hydrogenation with H2 over Pd/C in acetic acid, giving N-[2-(2-piperazinyl)ethyl]carbamic acid ethyl ester (VII). The cyclization of (VII) by means of sodium ethoxide in hot ethanol yields perhydropyrazino[1,2-c]pyrimidin-6-one (VIII), which is methylated with formaldehyde-formic acid to the 2-methyl derivative (IX). Finally, this compound is ethylated with ethyl iodide, tetrabutylammonium bromide and KOH in THF.