The condensation of N-benzylpiperazine (I) with ethyl isocyanate (II) in refluxing ether gives N-ethyl-4-benzyl-1-piperazinecarboxamide (III), which is debenzylated by hydrogenolysis with H2 over Pd/C in ethanol - HCl yielding N'-ethyl-1-piperazinecarboxarnide (IV). Finally, this compound is condensed with 1,1-bis(4-fluorophenyl)-4-chlorobutane (V) by means of NaHCO3 in refluxing ethanol.
3,4-Difluorobenzaldehyde (I) is condensed with methyl 4-methoxyacetoacetate (II) and urea in the presence of boron trifluoride etherate and copper (I) oxide to produce the dihydropyrimidinone adduct (III). After isolation of the desired enantiomer by means of chiral HPLC, reaction with p-nitrophenyl chloroformate leads to the nitrophenyl carbamate (IV). Then, condensation of (IV) with 3 bromoproylamine (V) furnishes the N-bromopropyl urea derivative (VI).
N-Boc-4-Piperidone (VII) is converted into the enol triflate (VIII) upon treatment with N-phenyl trifluoromethanesulfonimide and LDA. Subsequent Suzuki coupling of (VIII) with 3-acetamidophenylboronic acid (IX) yields the 4-aryl tetrahydropyridine (X). Removal of the N-Boc group of (X) under acidic conditions furnishes the deprotected tetrahydropyridine (XI). Optionally, catalytic hydrogenation of (X) gives rise to piperidine (XII), which is then deprotected by acidic treatment to produce (XIII).
Condensation of piperidine (XIII) with the N-bromopropyl derivative (VI) gives rise to the title compound. Alternatively, the title compound can be prepared by condensation of bromide (VI) with tetrahydropyridine (XI) to produce adduct (XIV), which is then hydrogenated over Pd/C.