帕瑞昔布钠杂质的合成

Synthesis of Impurity in Parecoxib Sodium

为有效控制帕瑞昔布钠原料药质量并建立质量标准,以2-溴苯基丙酮为起始原料,与四氢吡咯缩合后,经环合、脱去四氢吡咯、偶联、氧化、成磺酰胺、与丙酸酐缩合制得帕瑞昔布钠杂质N-((2-(5-甲基-3-苯基异恶唑-4-基)苯基)磺酰基)丙酰胺(9),并对其合成工艺进行了优化。优化条件后,杂质总收率为42.8%(以2-溴苯基丙酮计),纯度达99.0%(HPLC)。其结构经核磁、质谱确证。合成工艺合理可行、反应条件温和,制备的杂质纯度高,可作为帕瑞昔布钠药物质量控制的杂质对照品。

In order to effectively control the quality of parecoxib sodium and to establish quality standards,2-bromophenylacetone was used as the starting material,condensed with tetrandrine,and then cyclized,stripped of tetrandrine,coupled,oxidized,sulfonated,and condensed with propionic anhydride to obtain the Parecoxib Sodium impurity,N-(2-(5-methyl-3-phenylisoxazol-4-yl)phenyl)sulfonyl propanamide(2),the structure of which was confirmed by 1H NMR and MS,and the synthetic process was optimized,and purification with an overall yield about 42.8%(as 2-bromophenylacetone)and a purity of 99.0%(HPLC).The structure of impurity were confirmed by'H NMR and MS.The conditions for synthetic process were optimized.This synthetic process is reasonable and feasible,the reaction conditions are mild,and the impurity purity is high.It can be used as the reference substance for the quality control of parecoxib sodium.