The condensation of ethyl 2-aminobenzo[b]thiophene-3-carboxylate (I) with 2,4-difluoronitrobenzene (II) afforded the diaryl amine (III). The nitro group of (III) was then reduced to amine (IV) by catalytic hydrogenation over Pd/C. Then, cyclization of amino ester (IV) with N-methylpiperazine (V) using TiCl4 in hot anisole produced the target benzothienobenzodiazepine, which was finally isolated as the corresponding maleate salt.
In a related procedure, the condensation of 2-aminobenzo[b]thiophene-3-carbonitrile (VI) with 2,4-difluoronitrobenzene (II) produced the diaryl amine (VII). Reduction of the nitro group of (VII) using sodium hydrosulfite yielded diamine (VIII). Subsequent cyclization of amino nitrile (VIII) upon acidic treatment gave rise to the tetracyclic system (IX). This was then treated with refluxing N-methylpiperazine (V) to provide the title compound.