盐酸洛氟普啶的合成工艺  

A new method for preparing revaprazan hydrochloride

作　　者：宋伟国[1,2] 徐文方[1] 杨大伟 高东圣 张晓攀 

机构地区：[1]山东大学药学院,济南250012 [2]寿光富康制药有限公司,寿光262700

出　　处：《中国新药杂志》2013年第14期1694-1696,共3页Chinese Journal of New Drugs

摘　　要：目的:确定并优化盐酸洛氟普啶的合成工艺。方法:以硝酸胍为原料,经与2-甲基乙酰乙酸乙酯发生闭环反应制得2-氨基-4-羟基-5,6-二甲基嘧啶(3),(3)经三氯氧磷氯化后与1-甲基-1,2,3,4-四氢异喹啉缩合得2-氨基-4-[3,4-二氢-1-甲基-2(1H)-异喹啉基]-5,6-二甲基嘧啶(5),5再经乙酰化、与对溴氟苯缩合、及去乙酰化后成盐即得目标产物。结果:目标产物的化学结构经熔点(mp)、核磁共振氢谱(1H-NMR)和质谱(MS)确证。结论:本工艺操作简单,总收率由60%提高至71%,适合工业化生产。Objective： To optimize the synthetic route of revaprazan hydrochloride.Methods： The target compound（1） was synthesized from guanidine nitrate（2） as the starting material,by ring-closure with ethyl 2methylacetoacetate,chlorination,condensation with 1-methyl-1,2,3,4-tetrahydroisoquinoline yielding 2-amino-4[3,4-dihydro-1-methyl-2-（1H）-isoquinolinyl]-5,6-dimethylpyrimidine（5）;subsequently,acetylation of 5,condensation with 4-bromofluorobenzene and deacetylation,and then salification with dry HCl gas.Results： The structure of the target compound was confirmed by mp,1H-NMR and MS.Conclusion： This improved method has the advantage of simpler operation and increases total yield from 60% to 71%,thus it can be applied in industrialized production.

关 键 词：盐酸洛氟普啶 抗溃疡药 可逆性质子泵抑制剂 缩合反应 化学合成 

分 类 号：R914.5[医药卫生—药物化学]