Method for purifying cefozopran hydrochloride

A technology of cefozopran hydrochloride and a purification method, which is applied in the field of preparation of cefozopran hydrochloride, can solve problems such as large amount of solvent used, difficulty in removing solvent, complex process, etc., achieves easy industrial production, solves the problem of excessive dissolution residues, and reduces drug dosage Effect

CN113461716AActive Publication Date: 2021-10-01HAINAN HAILING CHEMIPHARMA CORP
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2021-10-01

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Abstract

The invention discloses a method for purifying cefozopran hydrochloride, and the method sequentially comprises the following steps: (1) mixing a cefozopran hydrochloride crude product and monobasic alkali in a molar ratio of 1: (2.1-3.0) to generate a cefozopran salt solution; (2) filtering out solid impurities from the cefozopran salt solution, adding hydrochloric acid to adjust the pH value to be neutral, and adding water to precipitate a cefozopran solid; (3) reacting the separated cefozopran solid with hydrochloric acid to prepare a primary refined cefozopran hydrochloride product; (4) carrying out vacuum drying on the primary cefozopran hydrochloride refined product to obtain the cefozopran hydrochloride refined product. According to the principle that the water solubility of the cefozopran is poor, the crude cefozopran hydrochloride is alkalized and then separated out, the residual amount of organic matter is reduced, excessive water is removed through vacuum drying, and the purer refined cefozopran hydrochloride is obtained.
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Description

technical field

[0001] The invention relates to the technical field of preparation of cefozopran hydrochloride, in particular to a purification method of cefozopran hydrochloride. Background technique

[0002] Cefozolam hydrochloride, its chemical name is: [[(6R,7R)-7-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methanol Oxyiminoacetamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]imidazo[1,2 -b] Pyridazinium hydroxide inner salt monohydrochloride, molecular formula: C19H17N9O5S2. HCl, molecular weight: 551.99, structural formula:

[0003]

[0004] Cefazolam hydrochloride is the fourth-generation cephalosporin for injection developed by Takeda Pharmaceutical Co., Ltd. in Japan. At present, it has been widely used in the treatment of various infectious diseases including neonatal infection in Japan as the drug of choice in the early stage of out-of-hospital infection. .

[0005] In the preparation process of cefazolam hydrochloride, from the intermedia...

Examples

Embodiment 1

[0026] A kind of purification method of cefozopram hydrochloride, comprises the following steps successively:

[0027] (1) cefzoram hydrochloride crude product is mixed with a monobasic base in a molar ratio of 1:2.1 to generate a cefzoram sodium solution;

[0028] (2) filtering the cefozopran sodium solution to remove solid impurities, then adding hydrochloric acid to adjust the pH to neutral, adding water to separate out the cefozopran solid;

[0029] (3) reacting the cefozopram solid and hydrochloric acid separated out to make the primary product of cefozopran hydrochloride;

[0030] (4) The primary fine product of cefozopran hydrochloride is then vacuum-dried to obtain cefozopran hydrochloride.

[0031] The alkali mass concentration in the excess alkali is 30% sodium hydroxide solution. The mass concentration of the hydrochloric acid is 10%. The step (2) is operated at a temperature of 0°C. The step (3) is operated at a temperature of 0°C. The vacuum drying is to stir...

Embodiment 2

[0033] A kind of purification method of cefozopram hydrochloride, comprises the following steps successively:

[0034] (1) cefzoram hydrochloride crude product is mixed with a monobasic base in a molar ratio of 1:3.0 to generate a cefzoram sodium solution;

[0035] (2) filtering the cefozopran sodium solution to remove solid impurities, then adding hydrochloric acid to adjust the pH to neutral, adding water to separate out the cefozopran solid;

[0036] (3) reacting the cefozopram solid and hydrochloric acid separated out to make the primary product of cefozopran hydrochloride;

[0037] (4) The cefozopran hydrochloride primary fine product is vacuum-dried to obtain the cefozopran hydrochloride fine product.

[0038] The monobasic alkali in the excess alkali is 80% potassium hydroxide solution in mass concentration. The mass concentration of the hydrochloric acid is 30%. The step (2) is operated at a temperature of 5°C. The step (3) is operated at a temperature of 40°C. Th...

Embodiment 3

[0040] A kind of purification method of cefozopram hydrochloride, comprises the following steps successively:

[0041] (1) cefzoram hydrochloride crude product is mixed with a monobasic base in a mol ratio of 1:2.5 to generate a cefzoram sodium solution;

[0042] (2) filtering the cefozopran sodium solution to remove solid impurities, then adding hydrochloric acid to adjust the pH to neutral, adding water to separate out the cefozopran solid;

[0043] (3) reacting the cefozopram solid and hydrochloric acid separated out to make the primary product of cefozopran hydrochloride;

[0044] (4) The cefozopran hydrochloride primary fine product is vacuum-dried to obtain the cefozopran hydrochloride fine product.

[0045] The monobasic base in the excess base is 50% potassium hydroxide solution. The mass concentration of the hydrochloric acid is 20%. The step (2) is operated at a temperature of 2°C. The step (3) is operated at a temperature of 20°C. The vacuum drying is to stir a...