摘要
目的合成莫西沙星杂质C,并对合成工艺进行优化。方法以1-环丙基-6,7-二氟-8-甲氧基-4-氧代-1,4-二氢-3-喹啉羧酸为原料依次经历醚键的断裂、螯合与(S,S)-2,8-二氮杂双环[4.3.0]壬烷缩合、最后脱去叔丁氧羰基保护基得到莫西沙星杂质C;对脱甲基试剂、反应温度、缚酸剂、螯合物与底物的投料比和反应时间等条件进行优化,考察了莫西沙星杂质C的总收率及产品质量。结果工艺优化后莫西沙星杂质C总收率为76.3%,并通过核磁共振氢谱和质谱对其结构进行了确证;HPLC检测产品的纯度大于99%。结论首次报道了莫西沙星杂质C的合成工艺路线,其工艺反应条件温和,操作易行、收率高。本研究为开发莫西沙星杂质C提供了信息和依据。
Objective To synthesize moxifloxacin impurity C and to optimize its synthetic route. Methods Moxifloxacin impurity C was synthesized from 1-cyclopropyl-6,7-difluoro-l,4-dihydro-8-methoxy-4-oxo-3- quinolinecarboxylic acid via cleavage of ether bond, chelation, condensation with （S, S）-2,8-diazabicyclo[4.3.0] nonane, finally, the removal of tert-butoxycarbonyl protecting group; demethylating reagent, temperature, deacid reagent, side chain and chelation feed ratio, reaction time and other investment conditions were optimized, for high yield and purity of the product. Results The molar yield of moxifloxacin impurity C was 76.3% after process optimization, and the structure of moxifloxacin impurity C is eluci^dated by 1H-NMR spectra and electrospray ionization mass spectrometry （ESI-MS） analyses; the purity of product is more than 99% by HPLC. Conclusion The synthetic route for moxifloxacin impurity C was firstly reported, and the reaction conditions were mild, the operation was easy and the yield was high. This study provides reference and basis for development ofmoxifloxacin impurity C.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2016年第2期117-121,共5页
Chinese Journal of Antibiotics
关键词
莫西沙星杂质C
合成
喹诺酮
Moxifloxacin impurity C
Synthesis
Quinolone
