Study On The Synthetic Technology Of Pramipexole Hydrochloride

Parkinson’s disease,as a common neurodegenerative disease in the elderly,prevalence of the world population is about 0.3%,the incidence rate increases with age,is second only to the first neurodegenerative disease of the Alzheimer’s disease.Survey data show that the number of cases of PD nearly two million in China.In the next period of time,the number of PD patients in China will account for about half of the world.PD is not completely cure with the main treatment strategy for symptomatic treatment.With the rapid development of global aging society,PD and its prescription drugs were attractted more attention in recent years.Pramipexole,which was developed by Boehringer Ingelheim company,is a complete agonist of the D₂/D₃dopamine receptors.Pramipexole is an effective monotherapy in treating early PD and an adjunctive therapy with levodopa in advanced PD.It could significantly improve motor symptoms of patients with good tolerability and safety.Also it was considered to possess neuroprotective properties and antidepressant activity,it has become the first line drug in treatment of PD.The synthesis process of pramipexole was improved by consulting relevant paper.2,6-Diamino-4,5,6,7-tetrahydrobenzothiazole（intermediate-2）,the key intermediate of pramipexole,was synthesized from 4-N-acetyl-amino-cyclohexanon viaα-bromination,Hantzsch reaction,hydrolysis reaction.（6S）-2,6-Diamino-4,5,6,7-tetrahydrobenzothiazole（intermediate-3）was synthesized from intermediate-2 by chiral resolution with an yield of36%,[α]_D²⁰=-94.0（C=1,Me OH）.Pramipexole,an antiparkinsonism drug,was synthesized from intermediate-3 via reductive amination with propionaldehyde and sodium borohydride,followed by salt formation with overall yield of 17%,increased by nearly10%,compared with the literature reported,and[α]_D²⁰=-67.5（C=1,Me OH）.The structure of the target compound was confirmed by ¹H-NMR and IR and the specific rotation met the requirement of Europe Pharmacopeia.