3-三氟甲基-5,6,7,8-四氢-1,2,4-三唑[4,3-α]吡嗪盐酸盐的合成  

Synthesis of 3-Trifluoromethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-α] pyrazine Hydrochloride

作　　者：韩迅[1] 汪默[1] 杨平[1] 苑仁强 姜心贝 王亚楼[1] 

机构地区：[1]中国药科大学药物化学教研室,江苏南京210009

出　　处：《化学试剂》2015年第3期270-272,共3页Chemical Reagents

基　　金：江苏省2013年度大学生创新创业指导基金资助项目(SZ13129)

摘　　要：乙二胺与氯乙酸乙酯经取代、环合反应制得2-哌嗪酮,2-哌嗪酮与Boc酸酐进行氨基保护反应后,再与五硫化二磷进行硫代反应制得4-(N-叔丁氧羰基)-2-哌嗪硫酮,其与三氟乙酰肼经取代、环合、脱叔丁氧羰基成盐,得标题化合物,总收率为45.7%(以氯乙酸乙酯计)。为磷酸西他列汀中间体的工业化生产提供了一条较理想的工艺路线。3-Trifluoromethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-α]pyrazine hydrochloride,the key intermediate of Stiagliptin phosphate,was synthesized from ethyl chloroacetate by substitution with ethylenediamine,cyclization,protection with（ Boc）2O,and reaction with P2S5 to give 4-（ N-tertbutoxycarbonyl）-2-piperazin thione,which was subjected to reacted with trifluoroacetyl,substitution,cyclization,deprotection followed by salt formation with an overall yield of about 45. 7%（ based on ethyl chloroacetate）. This work provides an ideal technological route for the industrial production of Sitagliptin phosphate intermediate.

关 键 词：DPP-Ⅳ抑制剂 磷酸西他列汀 中间体 合成 

分 类 号：R914.5[医药卫生—药物化学]