合成路线1

NPS-2143 can be obtained by coupling 2-chloro-6-[2(R)-oxiranylmethoxy]benzonitrile (I) with 1,1-dimethyl-2-(2-naphthyl)ethylamine (II) in ethanol at 50-60 C. Intermediates (I) and (II) can be obtained as follows: a) Treatment of 2-chloro-6-fluorobenzonitrile (III) with 18-crown-6 and potassium acetate in refluxing acetonitrile, followed by hydrolysis with NaOH in H2O provides 3-chloro-2-cyanophenol (IV), which is then condensed with 3-nitrobenzenesulfonic acid (2R)-2-oxiranylmethyl ester (V) in DMF by means of NaH to furnish 2-chloro-6-[2(R)-oxiranylmethoxy]benzonitrile (I). b) Treatment of 2-(aminomethyl)naphthalene (VI) with 2,4,6-triphenylpyrylium tetrafluoroborate in EtOH, followed by the reaction of the resulting compound dissolved in DMSO with the sodium salt obtained by treatment of 2-nitropropane (VII) with NaH in MeOH, gives the nitro derivative (VIII). Finally, reduction of the nitro group of (VIII) by hydrogenation over Ni Raney in EtOH yields 1,1,-dimethyl-2-(2-naphthyl)ethylamine (II).