Bromination of methyl toluate (I) with N-bromosuccinimide and benzoyl peroxide (Bz2O2) in refluxing CCl4 gives alpha-bromo-o-toluate (II), which is coupled with phenolic derivative (III) by means of K2CO3 in DMF to provide phenoxy derivative (IV). Saponification of the methyl ester group of (IV) by treatment with KOH in refluxing EtOH affords carboxylic acid (V), which is then converted into the desired compound via the corresponding acid chloride obtained by reaction with oxalyl chloride in CHCl3, followed by coupling with 4,6-diamino-2-methylquinoline (XII) by means of pyridine. Quinoline (XII) can be obtained as follows: Condensation of 4-aminoacetanilide (VII) with methyl acetoacetate (VIII) by heating in MeOH affords crotonate (IX), which is then subjected to cyclization in refluxing Dowtherm A to provide hydroxy quinoline (X). Methylation of (X) with dimethyl sulfate in refluxing toluene gives methoxy quinoline (XI), whose methoxy group is converted into an amino group with ammonium acetate and whose acetyl group is finally removed by hydrolysis with HCl.
5-Nitroisatin (VIII) is condensed with acetone in the presence of aqueous ammonia in an autoclave at 100 C to produce the quinolinecarboxamide (IX). Subsequent Hofmann rearrangement of (IX) with sodium hypochlorite produces the 4-amino quinoline (X). The nitro group of (X) is then reduced by catalytic hydrogenation over Pd/C to give the diaminoquinoline (VII).
Radical bromination of methyl ortho-toluate (XI) with N-bromosuccinimide in the presence of benzoyl peroxide affords the 2-(bromomethyl)benzoate (XII). This is then condensed with 4-ethylphenol (XIII) to furnish ether (XIV). Alkaline hydrolysis of the methyl ester group of (XIV) provides acid (XV), which is further activated as the corresponding acid chloride (XVI) with oxalyl chloride in chloroform. Finally, condensation of acid chloride (XVI) with the diaminoquinoline (VII) gives rise to the title compound.