摘要
目的为了加强对索法酮原料药的质量控制,合成索法酮原料中的3种主要杂质。方法以索法酮为起始原料,经酯化反应制得(E)-2-[5-(3-甲基-2-丁烯氧基)-2-[3-[4-(3-甲基-2-丁烯氧基)]苯基]丙烯酰基]乙酸乙酯(杂质A);以2,4-二羟基苯乙酮为起始原料,经取代、水解反应制得2-[2-乙酰基-5-(3-甲基-2-丁烯氧基)苯氧基]乙酸(杂质B);以2,4-二羟基苯乙酮为起始物,经过取代、羟醛缩合反应制得(E)-1-[2,4-二(3-甲基-2-丁烯氧基)苯基]-3-[4-(3-甲基-2-丁烯氧基)苯基]-2-烯丙酮(杂质C)。结果与结论索法酮3种杂质的结构经~1H-NMR、^(13)C-NMR和HR-MS谱确证;HPLC面积归一化法测定杂质A、B、C的纯度分别为97.2%、96.9%、97.3%。杂质A、B、C可作为索法酮原料药质量控制的对照品。
Three main impurities A, B and C of sofalcone were synthesized. Using sofalcone as starting material （ E ） -2- [ 5 - （ 3 -methyl-2-butenyloxy ） -2- [ 3-[4- （ 3-methyl-2-butenyloxy ） ] phenyl ] acryloyl ] ethyl acetate（impurity A） was synthesized through esterification. Using 2,4-dihydroxy acetophenone as starting material 2- [ 2-acetyl-5- （ 3-methyl-2-butenyloxy ） phenoxy ] acetic acid （ impurity B ） was synthesized through substitution, hydrolysis and （E） -1-[ 2, 4-bis （ 3-methyl-2-butenyloxy ） phenyl ]-3-E 4-（ 3-methyl-2-butenyloxy ） phenyl ] 2-ene-acetone（impurity C） was obtained through substitution, aldol condensation. The impurities A, B and C were characterized by ^1H-NMR, ^13C-NMR and HR-MS. The purities detected by HPLC normalization method were 97.2% ,96.9 % ,97.3 %. The synthesis of A, B, C impurities plays an important role in sofalcone quality control.
出处
《中国药物化学杂志》
CAS
CSCD
2016年第1期45-48,共4页
Chinese Journal of Medicinal Chemistry
关键词
索法酮
杂质
合成
质量控制
sofalcone
impurities
synthesis
quality control
