The cyclization of dimethyl 2-methoxymalonate (I) with formamidine (II) by means of sodium methoxide in methanol gives the dihydroxypyrimidine (III), which by reaction with POCl3 is converted into the dichloropyrimidine (IV). The condensation of (IV) with 5-fluoro-3-[3-(1-piperazinyl)propyl]-1H-indole (V) by means of DIPEA in refluxing acetonitrile affords intermediate (VI), which is finally dechlorinated by hydrogenation with H2 over Pd/C in aqueous ethanol.

The target compound can also be obtained by condensation of 5-fluoro-3-[3-(1-piperazinyl)propyl]-1H-indole (V) with 4-chloro-5-methoxypyrimidine (VII) by means of K2CO3 in toluene/ethyl acetate.

The intermediate 5-fluoro-3-[3-(1-piperazinyl)propyl]-1H-indole (V) has been obtained as follows: a) The condensation of 5-fluoro-1H-indole (VIII) with acrylic acid (IX) by means of acetic anhydride gives 3-(1H-indol-5-yl)propionic acid (X), which is reduced with LiAlH4 to 3-(1H-indol-5-yl)-1-propanol (XI). The tosylation of (XI) with tosyl chloride yields the tosylate (XII), which is condensed with 1-benzylpiperazine (XIII) in refluxing butyl acetate affording 3-[3-(4-benzylpiperazin-1-yl)propyl]-5-fluoro-1H-indole (XIV). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C yielding the target intermediate (V). b) The tosylate intermediate (XII) can also be condensed with ethyl piperazine-1-carboxylate (XVII) in refluxing butyl acetate giving 4-[3-(5-fluoro-1H-indol-3-yl)propyl]piperazine-1-carboxylic acid ethyl ester (XVIII), which is then decarboxylated with NaOH to the target intermediate (V). The intermediate 3-(1H-indol-5-yl)-1-propanol (XI) can also be obtained by direct cyclization of 4-fluorophenylhydrazine (XV) with dihydropyran (XVI) in hot propyleneglycol.