西格列汀十元环杂质的合成

Synthesis of the 10-Membered Ring Impurity of Antidiabetics Sitagliptin Phosphate

目的:为更好地对降血糖药磷酸西格列汀质量进行控制,合成了西格列汀原料药和制剂的有关物质(R)-10-(2,4,5-三氟苯基)-3-(三氟甲基)-6,7,10,11-四氢-[1,2,4]三唑并[3,4-c][1,4,7]三氮杂环葵烷-8,12(5H,9H)-二酮5。方法:以(R)-3-((叔丁氧羰基)氨基)-4-(2,4,5-三氟苯基)丁酸和3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-a]吡嗪盐酸盐为起始原料,经过缩合、氧化、关环三步反应得到西格列汀十元环杂质。化合物结构经~1H-NMR、MS谱确证,可作为磷酸西格列汀质量控制的杂质对照品。

Aim： （R）-10-（2,4,5-trifluorobenzyl）-3-（trifluoromethyl）-6,7,10,11-tetrahydro-[1,2,4]triazolo[3,4-c][1,4,7]triazecine-8,12（5H,9H）-dione was synthesized as a degradation product in order to studying the quality of Sitagliptin Phosphate. Method： It was obtained by condensation reaction, oxidation, reaction, ring- closing reactions with （R）-3-（（terl-butoxycarbonyl）amino）-4-（2,4,5-Trifluorophenyl）butanoic acid and 3-（trifluoromethyl）-5,6,7,8-tetrahydro-[1,2,4]triazolo [4,3-a]pyrazine as the starting material. And can be used as impurity for control of quality The structure was confirmed by 1H-NMR, MS.