合成路线1

Reaction of 2-(4-aminophenyl)ethanol (I) with bis(2-chloroethyl)amine hydrochloride (II) in butanol gives 2-[4-(1-piperazinyl)phenyl]ethanol (III), which is alkylated with diphenylbromomethane (IV) and potassium carbonate in dimethyl formamide to afford 2-[4-[4-(diphenylmethyl)-1-piperazinyl]phenyl]ethanol (V). Treatment of (V) with diketene (VI) in the presence of 4-dimethylaminopyridine in tetrahydrofuran yields 2-[4-[4-(diphenylmethyl)-1-piperazinyl]phenyl]ethyl acetoacetate (VII), which is finally condensed with 3-nitrobenzaldehyde (VIII) and methyl 3-aminocrotonate (IX) in isopropanol (1-5). This last condensation can be performed in two steps by reaction of compound (VII) with compound (VIII) in the presence of piperidine and acetic acid in benzene to give 2-[4-[4-(diphenylmethyl)-1-piperazinyl]phenyl]ethyl 2-(3-nitrobenzylidene)acetoacetate (X), which is finally treated with (IX) in isopropanol. An alternative procedure involves condensation of 3-nitrobenzaldehyde (VIII), diketene (VI), methyl 3-aminocrotonate (IX) and 3-hydroxypropionitrile (XI) in isopropanol to give 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 2-cyanoethyl ethyl diester (XII), which is hydrolyzed with sodium hydroxide to 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester (XIII). Compound (XIII) is finally esterified with compound (V) in a mixture of dimethylformamide and chloroform.