利培酮嘧啶中间体的合成工艺研究

Study on synthesis of a pyrimidine intermediate for risperidone

目的:优化利培酮嘧啶中间体的合成工艺,提高反应收率。方法:以2-氨基吡啶和α-乙酰基-γ-丁内酯为原料,经过环合和氢化制得非典型抗精神病药物利培酮的中间体3-(2-氯乙基)-2-甲基-6,7,8,9-四氢-4H-吡啶并[1,2-a]嘧啶-4-酮。结果:改进了合成工艺,简化了操作,总收率提高到68.2%。目标化合物结构经MS和1H-NMR谱确证。结论:改进后的合成工艺切实可行,适合工业化生产。

Objective：To optimize synthetic process of a pyrimidine intermediate for risperidone,and to increase the yield.Methods：3-（2-Chloroethyl）-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido [1,2-a] pyrimidin-4-one,the pyrimidine intermediate for the synthesis of the atypical antipsychotic agent risperidone,was synthesized from 2-aminopyridine and α-acetyl-γ-butyrolactone by cyclization and catalytic hydrogenation.Results：The synthetic process was improved,opera-tion was simplified and the overall yield was increased to 68.2%.The structure of the 3-（2-chloroethyl）-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido [1,2-a] pyrimidin-4-one was identified by MS and 1H-NMR.Conclusion：The improved synthetic process is practicable and suitable for large-scale manufacture.