The condensation of 2-nitrophenol (I) with 2,2,2-trrifluoroethyl p-toluenesulfonate (II) by means of K2CO3 in DMF gives 2-(2,2,2-trifluoroethoxy) nitrobenzene (III), which isreduced with H2 over PtO2 in ethanol yiedling the aniline (IV). The cyclization of (IV) with bis (2-chloroethyl)amine (V) and K2CO3 affords the piperazine (VI), which is condensed with 1-benzyl-3-(3-chloro-propyl)-5-methylpyrimidine-2,4(1H,3H)-dione (VII) by means of K2CO3 in refluxing acetonitrile to give the benzylated target compound (VIII). Finally, this compound is deprotected by hydrogenation with ammonium formate and Pd/C. The intermediate pyrimidine (VII) has been obtained by benzylation of thymine (IX) with benzyl bromide and K2CO3 to give the 1-benzylthymine (X), which is alkylated with 1-bromo-3-chloropropane and K2CO3 to the target intemediate (VII).

The intermediate arylpiperazine (VI) was prepared as follows: Reaction of 2,4-difluoronitrobenzene (I) with trifluoroethanol (II) in the presence of potassium tert-butoxide yielded the trifluoroethyl ether (III). After catalytic hydrogenation of the nitro group of (III), the resultant aniline (IV) was cyclized with bis(2-chloroethyl) amine hydrochloride (V) in a refluxing mixture of o-dichlorobenzene and n-hexanol to afford the target piperazine (VI).

5-Methyluracil (VII) was protected with SEM-Cl (VIII) to yield the 1-SEM derivative (IX), which was subsequently alkylated with 1-bromo-3-chloropropane (X) under phase-transfer conditions to provide chloride (XI). Alkylation of piperazine (VI) with chloride (XI) in the presence of NaI and K2CO3 furnished adduct (XII). The title compound was then obtained by deprotection of (XII) upon treatment with tetrabutylammonium fluoride in THF.

In a different protection strategy, sulfonylation of 5-methyluracil (VII) by means of p-toluenesulfonyl chloride under Schotten-Baumann conditions furnished the 1-tosyl derivative (XIII). This was condensed with 1-bromo-3-chloropropane (X), yielding chloride (XIV). Removal of the tosyl protecting group of (XIV) by hydrolysis with H2SO4 afforded 3-(3-chloropropyl)-5-methyluracil (XV). Finally, alkylation of piperazine (VI) with chloride (XV) led to the title compound.