Pramipexole Hydrochloride Synthesis Process Research

This dissertation is about the synthesis and process research of pramipexole dihydrochloride, which acts as an anti-Parkinson drug.Parkinson’s disease is a chronic progressive neurodegeneration disorder that is characterized by a gradual loss of dopaminergic neurons in the pars compacta of the substantianiga. Pramipexole is known as an amino-benzathiazole direct-acting dopamine receptor agonist effective in treating Parkinson’s disease; it bound selectively and with high affinity to dopamine D2-like receptors, with highest affinity at dopamine D3 receptors. It show strong agonistic activity to dopamine acceptor with excellent tolerance and safety in clinical research.dihydrochloride pramipexole is designated chemically as (S)-(-)-2-Amino-4,5,6,7-tetrahydro-6-(propyIamino)benzothiazole dihydrochloride. Original manufacturing process of the pramipexole requires the use of hazardous and difficult to handle reagents. There is, therefore, a need for developing alternative processes for improved yield and avoiding the use of hazardous and difficult to handle reagents.In this thesis succinic acid diethyl ester was sythesised by succinic acid on the condition of using concentrated sulfuric acid as a catalyst. Then 2,5-dioxo-cyclohexane-1,4-dicarboxylic acid diethyl ester was prepeared from succinic acid diethyl ester by the reaction of Claisen condensation. After then, the prepartation of 1,4-cyclohexanedione diethylene ketal was by the reaction of decarboxylation at a high temperature, and we got 1,4-cyclohexanedione monoethylene acetal by the selective deprotection. After that, at the presence of Pd-C by the reductive amination and deprotection reactions we obtained 4-propylamino-cyclohexanone. And pramipexole dihydrochloride was formed by the reaction of iodo, Hantzsch thiazole ring synthesis, chiral split using L-tartaric acid and salification reaction. At last the final product was synthesised successfully in an overall of 6.6%. The structure of intermediates and the final product were identified by IR, GS-MS, NMR and optical rotation.