6-Hydroxy-2(1H)-quinolinone (I) is alkylated with epichlorohydrin in the presence of K2CO3 in MeOH to afford 6-(2,3-epoxypropoxy)-2(1H)-quinolinone (II). Ring opening of the epoxide (II) with 3,4-dimethoxybenzylamine gives OPC-18790. This compound is also obtained by the reductive alkylation of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone (III) with 3,4-dimethoxybenzaldehyde.
The synthesis of the (+)-(R)-isomer of OPC-18790 has been published: The condensation of 6-hydroxyquinolin-2(1H)-one (I) with (S)-(+)-epichlorohydrin (II) by means of triethylamine in methanol gives (S)-(+)-6-(3-chloro-2-hydroxypropoxy)quinolin-2(1H)-one (III), which by reaction with KOH in isopropanol/water yields the (R)-(-)-epoxide (IV). Finally, this compound is condensed with 3,4-dimethoxybenzylamine (V) by heating its mixture at 80 C. The (+)-(R)-isomer is about 10-fold more potent than the (-)-(S)-isomer.