2-Ethyl-6-methyl-3,4-dihydropyrimidin-4-one (I) is alkylated with 4-(2-bromoethoxy)benzaldehyde (II) in the presence of NaH and LiBr to afford (III). Subsequent Knoevenagel condensation of benzaldehyde (III) with thiazolidine-2,4-dione (IV) employing piperidine/benzoic acid leads to the benzylidene thiazolidinedione (V), which is finally reduced to the title benzyl thiazolidinedione by catalytic hydrogenation over Pd/C.
In an alternative procedure, pyrimidinone (I) is alkylated with 4-(2-bromoethoxy)nitrobenzene (II) to produce (III). Reduction of nitro compound (III) by catalytic hydrogenation affords aniline (IV). After diazotization of amine (IV), the resultant diazonium salt is coupled to ethyl acrylate in the presence of CuI, yielding the 2-bromo-3-arylpropionate (V). Cyclization of bromo ester (V) with thiourea (VI) furnishes the iminothiazolidinone (VII), which is finally hydrolyzed under acidic conditions to the target thiazolidinedione.