匹伐他汀钙母核位置异构体的合成

Synthesis of Positional Isomer in the Nuclear Parent of Pitavastatin Calcium

目的:为控制匹伐他汀钙喹啉母核的质量,合成母核氟苯环位置异构体[[2-环丙基-4-(3-氟苯基)-3-喹啉基]甲基]三苯基溴化膦(1)。方法:以2-氨基苯甲腈和3-环丙基-3-氧代-丙酸甲酯为原料,经Friedlander反应、重氮化、Sandmeyer反应、Suzuki偶联反应、还原、溴代以及制备膦叶立德得到化合物1。结果:化合物1的结构经核磁共振氢谱(1H NMR)、磷谱(31P NMR)和氟谱(19F NMR)、红外光谱和质谱确证,总收率40%,HPLC纯度99.4%。结论:合成的杂质可以作为匹伐他汀钙喹啉母核质量控制的杂质对照品。

Objective: To perform the quality control of the nuclear parent of pitavastatin calcium,((2-cyclopropyl-4-(3-fluorophenyl)quinolin-3-yl)methyl)triphenylphosphonium bromide(1) were synthesized.Methods: The compound 1 were synthesized started from 2-aminobenzonitrile and methyl 3-cyclopropyl-3-oxopropanoate by the Friedlander reaction, diazotization, Sandmeyer reaction, Suzuki reaction, reduction, bromination and phosphorus ylide formation. Results and Conclusion: The compound 1 were synthesized and their chemical structures were confirmed by 1 H NMR, 31 P NMR, 19 F NMR, IR and MS.The total yields of target compounds were 40%(based on 2-aminobenzonitrile). Their purities were 99.4 % as determined by HPLC. Conclusion The synthesized impurity can be used as the reference substances in the quality control of the nuclear parent of pitavastatin calcium.