60725-36-2Relevant academic research and scientific papers
Old is Gold? Nefopam Hydrochloride, a Non-opioid and Non-steroidal Analgesic Drug and Its Practical One-Pot Synthesis in a Single Solvent for Large-Scale Production
Bodireddy, Mohan Reddy,Krishnaiah, Kiran,Babu, Prashanth Kumar,Bitra, Chaithanya,Gajula, Madhusudana Rao,Kumar, Pramod
, p. 1745 - 1751 (2017/11/24)
Nefopam hydrochloride is extensively used in most of the European countries until today as an analgesic because of its non-opiate (non-narcotic) and non-steroidal action with fewer side effects compared with opioid and other analgesics, which cause more troublesome side effects. A multikilogram synthesis of nefopam hydrochloride has been achieved in one pot using a single solvent (toluene). A ≥99.9% purity of the active pharmaceutical ingredient (API) was achieved in excellent overall yield (≥79%). The one-pot, five-step synthetic process involves formation of an acid chloride (3) from benzoylbenzoic acid (2) followed by amidation (4), reduction (5), cyclization (6), and formation of the hydrochloride salt (1). The major advantages include (i) use of a single solvent, (ii) >90% conversion in each step, (iii) a cost-effective and operationally friendly process, (iv) averting the formation of genotoxic impurities, and (v) improved overall yield (≥79%) provided by the one-pot operation. For the first time, we report the characterization data of API 1, intermediates 3, 4, and 5, and also a possible impurity (5a).
Analysis of nefopam by TLC-densitometry. A study of degradation mechanism in solutions under stress conditions
Starek, Malgorzata,Dabrowska, Monika,Tarsa, Monika
scheme or table, p. 262 - 269 (2012/04/11)
A new, simple, selective, precise and accurate thin-layer chromatographic method for quantification of nefopam hydrochloride in formulations has been established and validated. TLC F254 silica gel plates in combination with a mixture of chloroform : methanol : glacial acetic acid (9 : 2 : 0.1, v/v/v) as mobile phase were used. UV detection was performed densitometrically at a wavelength of 222 nm. The method was validated for linearity, precision, accuracy, selectivity and specificity in accordance with ICH guidelines. Nefopam hydrochloride was subjected to acid and alkaline hydrolysis at different temperatures. The degradation products were well resolved from the pure drug with substantially different RF values and absorption spectra. LC-MS/MS analysis was used to characterize the chemical properties of degradation products. The likely chemical structures of the major degradation products are 2-[(2-benzylbenzyl)( methyl)amino]ethanol, 2-[{2-[hydroxyl(phenyl) methyl]-benzyl)(methyl)-amino]?ethanol and diphenylmethanone.
