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。
Abstract
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
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Key words
benfotiamine /
related substance /
synthesis
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