The reductive alkylation of 3-chloroaniline (I) with L-S-trityl-N-Boc-cysteinal (II) in the presence of sodium triacetoxyborohydride produced amine (III). Chloroacetylation of (III) followed by cesium carbonate-induced cyclization of the resulting chloroacetamide (IV) furnished the protected piperazinone (V). The S-trityl group of (V) was deprotected by treatment with silver nitrate and pyridine, yielding thiol (VI), which was subsequently alkylated with ethyl iodide to give thioether (VII). Sulfur oxidation by means of magnesium monoperoxyphthalate in methanol afforded sulfone (VIII). Then, acid deprotection of the Boc protecting group of (VIII) provided the intermediate piperazinone (IX).

The regioselective protection of 4-hydroxymethylimidazole (X) with trityl chloride gave the 1-trityl imidazole (XI), which was further acetylated to afford acetate (XII). Alkylation of imidazole (XII) with 4-cyanobenzyl bromide (XIII), followed by solvolysis of the resulting imidazolium salt in refluxing methanol, produced the cyanobenzyl imidazole (XIV). Acetate hydrolysis and subsequent oxidation of alcohol (XV) furnished aldehyde (XVI). The title compound was obtained by reductive alkylation of piperazinone (IX) with aldehyde (XVI) in the presence of sodium triacetoxyborohydride.

The synthesis of the intermediate (chlorophenyl)piperazinone (VIII) has been reported by two procedures. The hydrochloride salt prepared from 3-chloroaniline (I) was treated with 2-oxazolidinone (II) at 160 C to produce the aryl ethylenediamine (III), which was subsequently protected as the N-Boc derivative (IV). Acylation of aniline (IV) with chloroacetyl chloride (V) gave the chloroacetamide (VI). This was then cyclized to the piperazinone (VII) by treatment with K2CO3 in hot DMF. Further acid deprotection of the Boc group of (VII) afforded the intermediate (VIII).

Protection of 4-(hydroxymethyl)imidazole (XII) with chlorotriphenylmethane provided the 1-tritylimidazole (XIII). Acetylation of (XIII) with acetic anhydride in pyridine gave acetate ester (XIV). The imidazole ring of (XIV) was then alkylated with alpha-bromo-p-tolunitrile (XV) to yield the imidazolium salt (XVI), from which the N-trityl group was removed upon heating with MeOH. The resulting acetoxymethyl imidazole (XVII) was then hydrolyzed to alcohol (XVIII) using LiOH, and further Swern oxidation of (XVIII) furnished aldehyde (XIX). Finally, reductive condensation of aldehyde (XIX) with piperazinone (VIII) in the presence of sodium triacetoxyborohydride produced the title compound.