Author(s)

Sureshbabu Jayachandra, Madhuresh Kumar Sethi^*, Vipin Kumar Kaushik, Vijayakrishna Ravi, Saiprasad Kottolla, Vikas Chandra Dev, Purbita Chakraborty

R & D, Mylan Laboratories Ltd., Hyderabad, India.

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.

Asymmetric Synthesis, Tuberculosis (TB), Human Immunodeficiency Virus (HIV), Mycobacterium tuberculosis, Mycobacterium africanus, Mycobacterium bovis, Directly Observed Treatment Short (DOTS), High Prevalence of Multi-Drug-Resistant (MDR) and Extensively Drug Resistant (XDR)

Jayachandra, S. , Sethi, M. , Kaushik, V. , Ravi, V. , Kottolla, S. , Dev, V. and Chakraborty, P. (2018) Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances. Green and Sustainable Chemistry, 8, 190-207. doi: 10.4236/gsc.2018.82014.