Preparation method of aztreonam dimer impurity

Abstract

The invention discloses a preparation method of an aztreonam dimer, which comprises the following steps: step 1, taking aztreonam tert-butyl ester as a starting material SM1, taking a BOC-protected aztreonam main ring as SM2, and reacting under the action of alkali to obtain a compound I; 2, hydrolyzing the compound I serving as a reaction substrate at the temperature of 20-30 DEG C under the action of acid to obtain a compound II; and step 3, dissolving the compound II and the compound III in a solvent, and reacting at the temperature of 20-30 DEG C under the action of alkali to obtain a compound IV aztreonam dimer impurity with the purity of 97% or above. The method is suitable for industrial production of impurity reference substances by manufacturers and is also suitable for self-made impurity reference substances. The method is used for controlling the quality of aztreonam, so that the quality of aztreonam products is ensured.

Description

technical field [0001] The invention relates to aztreonam, in particular to aztreonam dimer and a preparation method thereof, and belongs to the technical field of medicinal chemistry. Background technique [0002] Aztreonam was developed by Bristol-Myers Squibb (Bristol-Myers Squibb) in the United States. It was first launched in Italy in 1984, in Pakistan in 1986, and in Indonesia under the trade name AZACTAM in 1988. It is suitable for sensitive aerobic leather. Treatment of various infections caused by blue-negative bacteria, such as: urinary tract infection, lower respiratory tract infection, sepsis, intra-abdominal infection, gynecological infection, postoperative wound, burn, ulcer and other skin and soft tissue infections; it is also used to treat skin and soft tissue infections in hospitals Infection of the above types of infection. [0003] Since the polymer impurities of antibiotic drugs will have a relatively large adverse reaction to the human body, the State F...

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Problems solved by technology

[0005] Through literature research, it is found that the currently reported synthesis method of aztreonam dimer impurities (European Journal of Pharmaceutical Sciences 3 (1995) 281-291) is as follows: the concentration of aztreonam is prepared at 1% to 33%, and the pH of the reaction solution is adjusted =5, placed at 25°C for 60-80h through column separation and purification; this method has a low product yield and is difficult to separate and purify, which is not conducive to obtaining dimer impurities with high purity, and cannot meet the requirements of the "impurity external standard method" for ammonia Requirements for the control of aztreonam dimer impurities in qunan related substances