The Knoevenagel condensation of 1-methylpyrazole-4-carboxaldehyde (I) with malonic acid afforded the pyrazolylacrylic acid (II), which was further esterified with methanol and sulfuric acid, yielding ester (III). Catalytic hydrogenation of the unsaturated ester (III) in the presence of Pd/C gave the pyrazolylpropionate (IV). Claisen condensation of ester (IV) with methyl formate by using potassium tert-butoxide produced the (hydroxymethylene)propionate (V), which was subsequently cyclized with thiourea (VI) to furnish the thiouracil derivative (VII). Alkylation of (VII) with 4-fluorobenzyl chloride (VIII) gave rise to the thioether (IX). Regioselective alkylation of pyrimidine (IX) with tert-butyl iodoacetate produced the pyrimidinylacetate (X). The tert-butyl ester of (X) was then cleaved with trifluoroacetic acid yielding carboxylic acid (XI).
Suzuki coupling between 4-bromobenzaldehyde (XII) and 4-trifluoromethylbenzeneboronic acid (XIII) produced the biphenyl compound (XIV). The reductive amination of aldehyde (XIV) with N,N-diethyl ethylenediamine (XV) gave diamine (XVI) (1). This was finally coupled with the intermediate carboxylic acid (XI) to afford the title amide.