Font Size: a A A

Study On Synthesis Of Pregabalin And 2-substitutentpyrimidine Derivatives

Posted on:2009-03-21Degree:MasterType:Thesis
Country:ChinaCandidate:H LuFull Text:PDF
GTID:2121360245973046Subject:Physical chemistry
Abstract/Summary:PDF Full Text Request
We studied the synthesis ofpregabalin in the first section.Pregabalin is an anticonvulsant believed to have a mechanism of action similar to that of Neurontin,a drug intuoduced to the market by Warner-Lambert.It increases the concentration of GABA by activating GAD and therefore is useful as a therapeutic agent for the treatment of pain,convulsions,general anxiety related disorders and epileptic seizures.Pharmacology,pharmacokinetics and of pregabalin were discussed briefly in the paper.The synthetic routes and synthesis process of pregabalin are researched particularly. The parts are included as follows:1.We compare all the routes of the synthesis of pregabalin in a great deal of literature. After thinking about the economic benefit,the environment problems and the feasibility in chemical production,isovaeraldehyde and methyl cyanoacetate was used as the starting material to synthesize racemic 3-aminomethyl-5-methylhexanoicacid by condensation,addition,cyclization,aminolysis,Hoffman rearrangement.The target compound was obtained by resolution with(S)-(+)-mandelic acid.2.We optimized the synthesis process of 3-isobutylglutaric,and have solved the problem of the hydrolysis and decarboxylation to greatly improve the product yield to 88%.3.The chiral reagent(S)-(+)-mandelic acid was successfully applied in chemical resolution of(±)-3-(aminomethyl)-5-methylhexanoic acid,through related references and tests.A final product btought the enantiomeric purity up to 100%S with a yield of 60.2%.We studied the synthesis of four 2-substituentpyrimidine derivatives(2-hydroxypyrimidine, 2-aminopyrimidine,2-chloropyrimidine,2-(1-piperazinyl)pyrimidine)in the second section.Pyrimidine derivatives are very important intermediates in pharmaceutical and dyestuff fields,they are mainly used in the synthesis of sedativehypotic drugs and reactive dyeing.The impotant applications of 2-substituentpyrimidine derivatives in the field of organic synthesis,pharmaceutical and chemical engineering are reviewed.The synthetic routes and synthesis process of pyrimidine derivatives are researched particularly The parts are included as follows:1.Synthesis of 2-aminopyrimidine:The effect of reaction variables including meod of charging,different reaction temperature and times were investigated to improve the product yield to 85%.And the aftertreatment of reactions that suites industrial technology were found out by ourselves.2.Synthesis of 2-chloropyrimidine:2-Chloropyrimidine was prepared from raw material 2-hydroxypyrimidine and 2-aminopymidine respectively.By means of a great deal of experiments,we optimized the reaction condition and aftertreatment of reactions particularly to insteady the yield in 71.8%.3.Synthesis of 2-(1-piperazinyl)pyrimidine:The effect of reaction from 2-chloropyrimidine and anhydrous piperazine variables including method of charging and ratio of raw material were researched to reduce the side reactions.The yield was improved from 60%to 85%.
Keywords/Search Tags:pregabalin, synthetic routes, (S)-(+)-mandelic acid, chemical resolution, 2-hydroxypyrimidine, 2-aminopyrimidine, 2-chloropyrimidine, 2-(1-piperazinyl)pyrimi dine
PDF Full Text Request
Related items