耐多药结核病(MDR-TB)相关物质的鉴定、合成、分离及光谱表征

S. Jayachandra, M. Sethi, V. Kaushik, Vijayakrishna Ravi, Saiprasad Kottolla, V. Dev, Purbita Chakraborty
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引用次数: 0

摘要

采用高效液相色谱法对(2R)-2,3-二氢-2-甲基-6-硝基-2-[[4-[4-[4-(三氟甲氧基)苯氧基]-1-哌啶基]苯氧基]甲基]咪唑[2,1 -b]恶唑原料药中几种相关物质进行了痕量检测。所有相关物质都被快速表征,但发现一些杂质是中间体。通过NMR, FT-IR和HRMS技术进一步证实了所提出的结构。基于光谱数据;未知相关物质表征为1-(甲基磺酰基)-4-[4-(三氟甲氧基)苯氧基]哌啶;4-{4-[4-(三氟甲氧基)-苯氧基]哌啶-1-基}苯酚和4-{4-[4-(三氟甲氧基)苯氧基]哌啶-1-基}苯基甲烷磺酸盐;(2S)-3-(4-溴苯氧基)-2-羟-2-甲基丙基甲烷磺酸盐,(2S)-3-(4-溴苯氧基)-2-甲基丙烷-1,2-二基甲烷磺酸盐,(2S)-2-甲基-3-(4-{4-[4-(三氟甲氧基)苯氧基]-哌啶-1-基}苯氧基)-丙烷-1,2-二基甲烷磺酸盐,(S)-3-(4-(4-(三氟甲氧基)苯氧基)-丙烷-1,2-二基甲烷磺酸盐,(S)-3-(4-(4-(三氟甲氧基))-2-甲基丙烷-1,2-二醇及其相应的对映体,(2R)-2-[(4-溴-苯氧基)甲基]-2-甲基氯乙烷和(2R)-2-[(4-溴-苯氧基)甲基]-2-甲基-6-硝基-2,3-二氢咪唑[2,1-b][1,3]恶唑。并提出了这些相关物质形成的可能机理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances
Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data; unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine; 4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate; 4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3] oxazole. A possible mechanism for the formation of these related substances is also proposed.
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