合成路线1

Nitration of 3-chlorobenzoic acid (I) with KNO3 and H2SO4 produced 2,4-dinitro-5-chlorobenzoic acid (II) which, after conversion to acid chloride (III), was reacted with ammonia to give amide (IV). Displacement of the chlorine of (IV) with 4-fluorobenzylamine (V) furnished aminobenzamide (VI). The nitro groups were then reduced by hydrogenation over PtO2, and the resulting triamine (VII) was cyclized to benzimidazole (VIII) by means of formic acid. 5-Bromo-2-propoxybenzoic acid (X) was prepared from 5-bromosalicylic acid (IX) by alkylation with n-propyl iodide. Coupling of carboxylic acid (X) with amine (VIII) using EDC and HOBt afforded amide (XI), which was cyclized to the imidazoquinazoline (XII) in the presence of potassium tert-butoxide. Substitution of the bromine atom of (XII) with cuprous cyanide in NMP yielded nitrile (XIII). This was finally converted to the desired amide by hydrolysis to the carboxylic acid, followed by coupling with ammonia in the presence of EDC.