合成路线1

4-Bromophenethyl amine (I) was refluxed with ethyl formate to afford formamide (II). Cyclization of (II) employing polyphosphoric acid and phosphorus pentoxide at 200 C furnished 7-bromo-3,4-dihydroisoquinoline, which was isolated as the corresponding hydrochloride salt (III). Reduction of (III) with NaBH4 gave the tetrahydroisoquinoline (IV), that was nitrated with KNO3 and H2SO4 to provide (V). After protection of (V) as the N-Boc derivative (VI), reduction of the nitro group with concomitant hydrogenolysis of the bromine by hydrogenation over Pd/CaCO3 yielded aminoisoquinoline (VII). This was coupled with 4’-(trifluoromethyl)biphenyl-2-carboxylic acid (VIII) by means of EDC to produce amide (IX). Cleavage of the Boc group of (IX) with trifluoroacetic acid gave amine (X). Finally, reductive alkylation of (X) with imidazole-2-carbaldehyde (XI) and sodium cyanoborohydride furnished the title compound.