合成路线1

The condensation of 2-(4-nitrophenyl)ethyl bromide (I) with 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (II) by means of K2CO3 and KI in DMF at 100 C gives 6,7-dimethoxy-2-[2-(4-nitrophenyl)ethyl]-1,2,3,4-tetrahydroisoquinoline (III), which is reduced with H2 over Pd/C in ethanol to yield the corresponding amine (IV). Finally, this compound is condensed with 5-methoxy-9-oxo-9,10-dihydroacridine-4-carboxylic acid (V) by means of DCC and HOBt in DMF to afford the target carboxamide. The intermediate 5-methoxy-9-oxo-9,10-dihydroacridine-4-carboxylic acid (V) has been obtained as follows: The condensation of 2-amino-3-methoxybenzoic acid (VI) with 2-bromobenzoic acid (VII) by means of K2CO3 and copper dust give the diphenylamine (VIII), which is cyclized to the target acridine (V) by means of POCl3 in refluxing acetonitrile.

合成路线2

Condensation of 1,4-diacetyl-2,5-piperazinedione (I) with the equimolecular amount of benzaldehyde in the presence of triethylamine affords the benzylidene compound (II), which is N-methylated on treatment with iodomethane and sodium hydride to give III. Alkylation of the tetrahydroisoquinoline (V) with 4-(2-bromoethyl)nitrobenzene (IV) provides the tertiary amine (VI). The nitro group of (VI) is reduced by treatment with iron powder and concentrated HCl in refluxing MeOH to give aniline VII, which is condensed with 3-formylbenzoic acid (VIII) in the presence of 2-chloro-1-methylpyridinium iodide to afford the corresponding amide (IX). Finally, condensation between the previously obtained piperazinedione (III) and aldehyde (IX) in the presence of Cs2CO3 leads to the title compound.

合成路线3

Amine (I) was alkylated with 4-nitrophenethyl bromide (II) in refluxing isopropanol to yield the tertiary amine (III). Hydrogenation of the nitro group of (III) employing Pd/C afforded aniline (IV). Subsequent condensation of (IV) with methanesulfonyl chloride in the presence of Et3N produced the corresponding sulfonamide. The title compound was finally isolated as the hydrochloride salt.

合成路线4

The acylation of piperazine (II) with 4-nitrobenzoyl chloride (I) afforded a mixture of monoacylated (III) and diacylated (IV) products, which were separated by chromatography. Subsequent alkylation of monosubstituted piperazine (III) with 4-nitrophenethyl bromide (V) in the presence of K2CO3 and NaI yielded the title compound.

合成路线5