Abstract: The present disclosure discloses nitrosamine impurities, a varenicline pharmaceutical composition capable of reducing the generation of nitrosamine impurities, and the preparation and use thereof. By means of adding a pharmaceutically acceptable acid to a secondary amine compound or a composition thereof, the pharmaceutical composition of the present disclosure can effectively inhibit and reduce the generation of nitrosamine impurities, improve the stability of the secondary amine compound or the composition thereof, and control the content of genotoxic nitrosamine impurities to be at a relatively low level, so as to comply with safety requirements.

Abstract: Disclosed is a method for preparing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) of formula (II), comprising the following steps: carrying out an alkylation reaction on cyclen in formula (I) and XCH2COOR in the presence of an acid-binding agent in water; adjusting a pH value to separate out a crude product of DOTA; and recrystallizing. The preparation method of the present invention is applicable to large-scale industrial production of DOTA, the whole process does not need to adopt an ion-exchange resin or low-temperature refrigeration mode for purification, and the purity and yield of the product are higher.

Abstract: The present invention provides a preparation method for Efinaconazole, comprising the following steps: in the presence of a bromide and a base, subjecting (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazole-1-yl)methyl]oxirane and an inorganic acid salt of 4-methylenepiperidine to a ring-opening addition reaction in a reaction solvent, to obtain Efinaconazole. The preparation method for Efinaconazole in the present invention has mild reaction conditions, high product yield, high purity, and low production costs, and is suitable for industrial production.

Abstract: Disclosed is a method for preparing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) of formula (II), comprising the following steps: carrying out an alkylation reaction on cyclen in formula (I) and XCH2COOR in the presence of an acid-binding agent in water; adjusting a pH value to separate out a crude product of DOTA; and recrystallizing. The preparation method of the present invention is applicable to large-scale industrial production of DOTA, the whole process does not need to adopt an ion-exchange resin or low-temperature refrigeration mode for purification, and the purity and yield of the product are higher.