苯磷硫胺有关物质的合成  

Synthesis of the Related Substances of Benfotiamine

作　　者：陈梦婷 田文军 郭晔堃[1] 钟静芬[1] CHEN Mengting;TIAN Wenjun;GUO Yekun;ZHONG Jingfen(Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203)

机构地区：[1]中国医药工业研究总院上海医药工业研究院,上海201203

出　　处：《中国医药工业杂志》2020年第3期367-370,共4页Chinese Journal of Pharmaceuticals

摘　　要：本研究合成了苯磷硫胺2个有关物质,即3-[(4-氨基-2-甲基嘧啶-5-基)甲基]-5-[2-[[羟基(膦酰氧基)膦酰基]氧基]乙基]-4-甲基-1,3-噻唑-3-鎓氯化物(5)和二磷酸单-[4-[(4-氨基-2-甲基嘧啶-5-基甲基)-甲酰基-氨基]-3-苯甲酰基硫基-戊-3-烯基]酯(6)。氯化3-[(4-氨基-2-甲基-5-嘧啶基)-甲基]-5-(2-羟乙基)-4-甲基噻唑鎓盐酸盐(2)与多聚磷酸反应得粗品5,经D301阴离子交换树脂柱纯化,减压浓缩,加异丙醇析出5,纯度96.55%。5在碱性条件下,低温与苯甲酰氯反应,经冷冻干燥得6,纯度97.57%。产物结构经MS、1H NMR和13C NMR确证。Two related substances of benfotiamine,named 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-[2-[[hydroxy(phosphonooxy)phosphoryl]oxy]ethyl]-4-methyl-1,3-thiazol-3-ium chloride(5)and diphosphoric acid mono-[4-[(4-amino-2-methylpyrimidin-5-ylmethyl)-formyl-amino]-3-benzoylsulfanyl-pent-3-enyl]ester(6),were synthesized in this report.3-[(4-Amino-2-methyl-5-pyrimidinyl)-methyl]-5-(2-hydroxyethyl)-4-methylthiazolium chloride hydrochloride(2)reacted with polyphosphoric acid to obtain the crude product 5,which was purified with a D301 anion exchange resin column,and the eluent was concentrated under reduced pressure.Isopropanol was added to precipitate 5 with a purity of 96.55%.Compound 5 reacted with benzoyl chloride in the presence of alkali at low temperature to give 6,which was followed by freeze-drying,with a purity of 97.57%.The product structures were confirmed by MS,1H NMR and 13C NMR.

关 键 词：苯磷硫胺 有关物质 合成 

分 类 号：R914.5[医药卫生—药物化学]