帕潘立酮的合成  

Synthesis of Paliperidone

作　　者：王超[1] 禹艳坤[1] 刘爱霞[1] 冀亚飞[1] 

机构地区：[1]华东理工大学药学院,上海200237

出　　处：《中国医药工业杂志》2010年第10期721-723,共3页Chinese Journal of Pharmaceuticals

摘　　要：2-氨基-3-羟基吡啶经氯苄保护后,与α-乙酰基-γ-丁内酯环合得9-苄氧基-3-(2-羟乙基)-2-甲基-4H-吡啶并[1,2-a]嘧啶-4-酮(4),经氯化、还原并脱苄得到关键中间体3-(2-氯乙基)-6,7,8,9-四氢-9-羟基-2-甲基-4H-吡啶并[1,2-a]嘧啶-4-酮(6)。6与6-氟-3-(4-哌啶基)-1,2-苯并异噁唑盐酸盐经亲核取代制得帕潘立酮,总收率约35%。2-Amino-3-hydroxypyridine reacted with benzyl chloride to give 2-amino-3-benzyloxypyridine（3）,which was cyclized with α-acetyl-γ-butyrrolactone to provide 9-benzyloxy-3-（2-hydroxyethyl）-2-methyl-4H-pyrido[1,2a]pyrimidin-4-one（4）.Compound 4 underwent chlorination,reduction and debenzylation to afford the key intermediate 3-（2-chloroethyl）-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one（6）.Finally,compound 6 was subjected to nucleophilic substitution with 6-fluoro-3-（4-piperidinyl）-1,2-benzoisoxazol hydrochloride to achieve the title product paliperidone with an overall yield of about 35%.

关 键 词：帕潘立酮 多巴胺D2受体和5-HT2A受体双重拮抗剂 精神分裂症 合成 

分 类 号：R971.41[医药卫生—药品]