合成路线1

The reaction of ethyl 4-bromoacetoacetate (I) with 2-chloroethanol (II) by means of NaH in THF gives ethyl 4-(2-chloroethoxy)acetoacetate (III), which is treated with NaI in refluxing acetone to yield the corresponding 2-iodoethoxy derivative (IV). The condensation of (IV) with 2-chlorobenzaldehyde (V) by means of piperidine acetate in isopropanol affords ethyl 2-(2-chlorobenzylidene)-4-(2-iodoethoxy)acetoacetate (VI), which is cyclized with methyl 3-aminocrotonate (VII) in refluxing isopropanol to provide the dihydropyridine (VIII). The reaction of (VIII) with hexamethylenetetramine (IX) in hot acetonitrile gives the aminium salt (X), which is finally treated with benzenesulfonic acid in refluxing butanol (methanol)/water. Alternatively, the intermediate dihydropyridine (VIII) can be obtained as follows: The condensation of ethyl 4-(2-chloroethoxy)acetoacetate (III) with the aldehyde (V) by means of piperidine acetate in isopropanol gives ethyl 2-(2-chlorobenzylidene)-4-(2-chloroethoxy)acetoacetate (XI), which is cyclized with methyl 3-aminocrotonate (VII) in refluxing isopropanol to yield the corresponding dihydropyridine (XII). Finally, this compound is treated with NaI in refluxing isopropanol to afford the target intermediate dihydropyridine (VIII).