Nemonoxacin malate active pharmaceutical ingredient with low combination impurities, and a preparation method thereof

A method for preparing a nemonoxacin malate API, comprising the following steps:

• 1) Providing a C1-C3 alcohol/water mixed solvent in which nemonoxacin free base and D,L-malic acid are dissolved, the temperature of the mixed solvent is 50° C.-65° C.,
• wherein, a feeding mole ratio of the D,L-malic acid to the nemonoxacin free base is 0.95:1.0-1.2:1.0, the use amount of the C1-C3 alcohol/water mixed solvent is 8-14 times the weight of the nemonoxacin free base, and a weight ratio of the water to the C1-C3 alcohol is 0.4-0.7:1;
• 2) Performing cooling crystallization on a mixed solution obtained in the step 1), and then performing solid-liquid separation, washing and drying on a precipitated solid, so as to obtain the nemonoxacin malate API;
• the cooling crystallization refers to direct cooling crystallization;
• and the direct cooling crystallization comprises:
• cooling the mixed solution to room temperature, and then performing cooling to −10° C.-20° C. by means of an ice bath for crystallization;
• or
• the cooling crystallization refers to gradient cooling crystallization, the gradient cooling crystallization comprises the following steps:
• (i) cooling the mixed solution to 35° C.-45° C., then holding the temperature and performing stirring for 0.5-6 h;
• (ii) cooling filtrate obtained in the step (i) to −10° C.-20° C. for crystallization;
• (iii) filtering the filtrate after the crystallization, washing a filter cake with ethanol, and then performing vacuum drying on the filter cake at 20° C.-65° C. so as to obtain the nemonoxacin malate API.