Use of interphase catalysis in the synthesis of 2-acyl-4-oxopyrazino[2,1-?]isoquinolines and 4-acyl-2-piperazinones

Praziquantel – 50 Years of Research

“…[45] The transformation from 25 to 6 can be done in analogy to the reaction from 2 to 4, described above or in one pot reaction of aqueous alkali under PTC catalysis. [46] For the sake of completeness, it should be mentioned that 23 is easily accessible from 7 through Bischler-Napieralski reaction. [47] However, 23 has a reputation for being difficult to handle.…”

“…To save the isolation of intermediate (R)-3 we applied the already mentioned one pot reaction under PTC catalysis. [46] Several non-GMP and GMP pilot plant batches have been synthesized accordingly. But the cost that we saved through the one-pot process was exceeded by the cost of additional purification steps due to dimeric impurities formed in this process.…”

“…Once again, this might be a matter of stereochemical hinderance as already mentioned in combination with a higher basicity of the secondary amine [45] . The transformation from 25 to 6 can be done in analogy to the reaction from 2 to 4 , described above or in one pot reaction of aqueous alkali under PTC catalysis [46] …”

“…An intensive salt screening of the chiral standard acids showed (2S,3S)‐ dibenzoyltartaric acid is the best to get (R)‐ 2 (R 1 =CH 3 ) (Scheme 7). To save the isolation of intermediate (R)‐ 3 we applied the already mentioned one pot reaction under PTC catalysis [46] . Several non‐GMP and GMP pilot plant batches have been synthesized accordingly.…”