| Robenacoxib is a non-steroidal anti-inflammatory drug developed by Novartis Ag in2001 for the treatment of pain and inflammation in cats and dogs and is available in tablet and injectable form.In this paper,the synthetic route of robenacoxib was investigated and the conditions parameters of the synthetic route suitable for industrial production were optimized to obtain a low cost and high quality robenacoxib API in preparation for the next step of industrial production.In this paper,the synthetic route of robenacoxib was firstly investigated.The simple and easily available p-ethylaniline and pentafluorobenzene were chosen as the starting materials,and the crude product of Robenacoxib was obtained by substitution,acylation,hydrolysis and reduction reactions.Finally,the refined product of robenacoxib was obtained by refining.Through the exploration of reaction ratios,reaction time,temperature and other parameters,the optimal ratios and reaction conditions for the synthetic route of robenacoxib have been confirmed.The total yield of the reaction was mostly above 50%after the stability verification of several batches of small trials.The reaction conditions of this route are mild,environmentally friendly and suitable for industrial production.Based on the optimized synthesis process of robenacoxib,the preparation of robencoxib standards was carried out,and then the content of self-made robenacoxib standards was obtained by the calibration and content confirmation of the prepared selfmade robenacoxib standards,which were then analyzed by primary mass spectrometry and secondary mass spectrometry fragments combined with nuclear magnetic(NMR),infrared spectroscopy(FT-IR)and ultraviolet(UV)spectroscopy results.The results confirmed that the sample was structurally compatible with robenacoxib and could be used as a control in the subsequent drug development,production and quality control processes.Based on the 2020 edition of the Chinese Veterinary Pharmacopoeia,we initially established the quality standard of this product.Combined with the synthesis process of Robecoxib,we have established preliminary methods for the identification of Robecoxib,residual solvents and related substances. |
