| Pramipexole dihydrochloride, an effective anti-Parkinson drug with chemical name of (S)-2-amino-6-(propylamino)-4,5,6,7-tetrahydrobenzo-thiazole dihydrochloride, is a new non-ergot dopamine agonists with high selectivity and sufficient affinity to the D2dopamine acceptor family, and has a good tolerability and safety widely used in the clinical treatment of Parkinson. Meanwhile, it shows broad application prospect and tremendous market potential.Firstly, in this thesis, the synthesis technology of pramipexole dihydrochloride were studied. With reference to the literatures, the synthesis route of pramipexole dihydrochloride was proposed. Pramipexole dihydrochloride was prepared from acetaminophen cyclohexanone through five-step reaction, such as Hantzsch reaction, deacetylation, resolution, propylation and salification. The optimal synthesis processes of the product was obtained through orthogonal experiments. The optimal synthesis processes of product were as follows:(1) the Hantzsch reaction:solvent was acetic acid, molar ratio of acetaminophen cyclohexanone and thiourea was1:2, reaction temperature was50-60℃.(2) spilt reaction:the reagent was L-(+)-tartaric acid, reaction temperature was75℃, and the product was recrystallized for two times.(3) the acylation reaction:acylating agents was propionic anhydride, reaction temperature was-10℃.(4) reduction reaction: reduction reagen was NaBH4/I2, and the molar ratio of reduction reagen to raw material was1:2.4:4, the charging sequence was sodium borohydride-raw material-iodine.Secondly, the structure of the as-synthesized compound was confirmed by UV, FT-IR, NMR, elemental analysis, thermal analysis and XRD. The results show that the as-synthesized compound is the target product.Finally, the quality of pramipexole dihydrochloride was studied by determining its physicochemical properties, impurities, contents and optical isomers. The results showed that the technological conditions of this thesis can be applied to the industrial production. |
PDF Full Text Request