The Synthesis Of Somatostatin Receptor Antagonist, N-Methyl-N-Propyl Piperazine (9H-fluoren-9-yl) Ethyl Amino Derivatives

ObjectivesOur study is aim to synthesize non-peptide SSTR antagonists, fluorene derivatives, which have high affinity and high selectivity with tumor expressing SSTR on the surface. So far, radio labeled fluorene derivatives has not been founded. According to the chemical structure of N-methyl-N-propyl piperazine (9H-fluoren-9-yl) ethyl amino derivatives, an appropriate positron radioactive labeled precursor was sythesized, which is the basis of the further labeling for targeting positive SSTR tumor molecular probe.MethodsThe synthetic method is mainly divided into two modules. One module is to synthesize the fluorine acetamide, the other module is to synthesize the piperazine derivatives. Coupling reaction is taken by two module to obtain the product of N-methyl-N propyl piperazine fluorene ethylamine derivatives.There are totally three synthetic strategies used for N-methyl-N-propyl piperazine (9H-fluoren-9-yl) ethyl amino derivative. Plan One, Coupling Reaction Following with Methylation, is named by the procedure of the above-mentioned two modules firstly coupling with each other and following by single methylation reaction to obtain the production. Plan Two, Reductive Amination Following with Methylation and Coupling Reaction, is named by the procedure of the reductive amide firstly obtaining by reduction reaction and following with single methylation and the last step coupling with piperazine. Plan Three, Methylation Following with Coupling Reaction, is named by the procedure of the methylated fluorene amide synthesized from the crude material fluorene acetic acid, and following with reduction reaction and coupling with Module Two piperazine to obtain the production.ResultAfter tests of above methods, we have successfully synthesized the precursor of N-methyl-N-propyl piperazine (9H-fluoren-9-yl) ethyl amino derivatives by Plan Three which has the advantages of simple steps, easy completion. It ensures the connection of single methyl group structure, and improves the yield rate and the synthesis efficiency. Synthesis of Standard with four steps reaction, which has been completed to the thrid step reaction. Plan Three is the best synthetic solution.GonclusionWe have successfully synthesized the precursor of N-methyl-N-propyl piperazine (9H-fluoren-9-yl) ethyl amino derivatives. Standard of N-Methyl-N-propyl piperazine (9H-fluoren-9-yl) ethyl amino derivatives has been completed to the third step reaction. These are the basis of the further positron radionuclide labeling for targeting positive SSTR tumor molecular probe.