Preparation method of faropenem sulfone
By oxidizing faropenem with organic solvents and oxidants at low temperatures to prepare faropenem sulfone, the degradation problem of faropenem sodium under thermal, acid-base, and oxidative conditions was solved, enabling the preparation of high-purity faropenem sulfone and enhancing the foundation for drug quality research.
Patent Information
- Application Number
- CN202411124610.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-16
- Publication Date
- 2026-03-03
AI Technical Summary
The lack of existing methods for preparing faropenem sulfone affects drug quality and stability, especially since faropenem sodium is easily degraded under heat, acid, alkali and oxidative conditions.
Faropenem sulfone is prepared by oxidizing faropenem with organic solvents such as dichloromethane or tetrahydrofuran and oxidants such as m-chloroperoxybenzoic acid at low temperature. The reaction conditions are mild and the purity is high.
This method enables the simple and efficient preparation of faropenem sulfone with high product purity, and serves as a reference standard for faropenem-related substances, thus improving the foundation for drug quality research.
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Figure CN121591754A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a method for preparing faropenem sulfone. Background Technology
[0002] Faropenem sodium is a novel broad-spectrum antibacterial drug developed and marketed by Suntory Pharmaceutical Co., Ltd. of Japan in 1997. This drug is an atypical lactam penicillin with strong antibacterial activity, particularly against Gram-positive bacteria such as Staphylococcus aureus, penicillin-resistant pneumococci, and Enterococcus faecalis, as well as anaerobic bacteria such as Bacteroides fragilis. Its antibacterial activity against Gram-negative bacteria is similar to that of oral cephalosporins, and it is stable against various lactamases.
[0003] Impurity research is a key research area in drug development and commercial production, and it is conducted throughout the entire drug lifecycle. The presence of impurities directly affects the safety, efficacy, and quality control of drugs.
[0004] Faropenem sodium exhibits poor stability, degrading under heat, acidic, alkaline, and oxidative conditions. Faropenem sulfone is an impurity resulting from the oxidation of sulfur in the faropenem sodium structure, and its content significantly affects drug quality. Therefore, research on the synthesis of faropenem sulfone is essential; however, no relevant literature reports a method for its preparation.
[0005] In view of the above, the present invention provides a method for preparing faropenem sulfone. Summary of the Invention
[0006] The purpose of this invention is to provide a method for preparing faropenem sulfone.
[0007] This invention provides faropenem sulfone (compound of formula II), the structural formula of which is as follows:
[0008] This invention also provides a method for preparing faropenem sulfone (compound of formula II), comprising the following steps: oxidizing faropenem (compound of formula I) in an organic solvent with an oxidizing agent to prepare faropenem sulfone (compound of formula II).
[0009] The organic solvent used in the step is selected from dichloromethane, tetrahydrofuran, and acetonitrile. The volume of the organic solvent is 5-20 times (mL / g) the mass of the compound of Formula I, preferably 10 times.
[0010] The reaction temperature in the above steps is -20 degrees to 25 degrees, preferably 0 degrees.
[0011] In the step, the oxidant is selected from m-chloroperoxybenzoic acid and hydrogen peroxide, preferably m-chloroperoxybenzoic acid.
[0012] In the step described above, the molar ratio of the oxidant to the compound of formula I is 2 to 5:1, preferably 2:1.
[0013] The reaction time for the step is 2-24 hours, preferably 6 hours.
[0014] Due to the application of the above technical solutions, this invention has the following advantages: a short route, simple operation, mild reaction conditions, and high product purity. The faropenem sulfone (compound of formula II) prepared by this invention can be used as a reference standard for faropenem-related substances, providing a basis for the quality research of faropenem. Attached Figure Description
[0015] Figure 1 This is the high-performance liquid chromatogram of faropenem sulfone (compound of formula II) in Example 1.
[0016] Figure 2 This is the mass spectrum of faropenem sulfone (compound of formula II) in Example 1.
[0017] Figure 3 This is the 1H NMR spectrum of faropenem sulfone (compound of formula II) in Example 1. Detailed Implementation
[0018] It should be understood that those skilled in the art can make various modifications and improvements to the invention without departing from the spirit and scope of the invention, based on the content disclosed herein. All such modifications and improvements should fall within the patent protection scope defined by the claims of this application. Furthermore, it is understood that the embodiments provided herein are for illustrative purposes only and should not be construed as limiting the invention.
[0019] The present invention will be further described in detail below with reference to specific embodiments.
[0020] Example 1: Preparation of faropenem sulfone (compound of formula II): 1 g of compound I (faropenem) was dissolved in 10 ml of dichloromethane, cooled to 0°C, and 1.61 g of m-chloroperoxybenzoic acid was added. The reaction mixture was reacted at 0°C for 6 hours. The reaction solution was evaporated to dryness and purified by preparative liquid chromatography to obtain 0.39 g of faropenem sulfone (compound of formula II). The product was a yellow solid, and the characterization data are as follows: Figure 1 High performance liquid chromatography purity: 95.52%. Figure 2 Mass spectrometry: [M+H] + =318.0628, [M+NH4] + =335.0895, [M+Na] + =340.0438, [2M+NH4] + =652.1451, [2M+Na] +=657.0994, Figure 3 1H NMR spectrum (400MHz, D2O).
[0021] Example 2: Preparation of faropenem sulfone (compound of formula II): 1 g of compound I (faropenem) was dissolved in 10 mL of tetrahydrofuran, cooled to 0°C, and 2.42 g of m-chloroperoxybenzoic acid was added. The mixture was reacted at 0°C for 6 hours. The reaction solution was evaporated to dryness and purified by preparative liquid chromatography to obtain 0.3 g of faropenem sulfone (compound of formula II). It was a yellow solid with an HPLC purity of 96.85%.
[0022] Example 3: Preparation of faropenem sulfone (compound of formula II): 1 g of compound I (faropenem) was dissolved in 10 ml of dichloromethane, cooled to 0°C, and 1.61 g of m-chloroperoxybenzoic acid was added. The mixture was reacted at room temperature for 10 hours. The reaction solution was evaporated to dryness and purified by preparative liquid chromatography to obtain 0.25 g of compound II (i.e., faropenem sulfone). It was a yellow solid with an HPLC purity of 95.21%.
Claims
1. The structural formula of a faropenem sulfone (compound of formula II) is as follows:
2. A method for preparing faropenem sulfone (compound of formula II), characterized in that: The method includes the following steps: oxidizing faropenem (compound of formula I) in an organic solvent with an oxidizing agent to prepare faropenem sulfone (compound of formula II).
3. The method as described in claim 2, characterized in that: The organic solvent used in the step is selected from dichloromethane, tetrahydrofuran, and acetonitrile. The volume of the organic solvent is 5-20 times (mL / g) the mass of the compound of Formula I, preferably 10 times.
4. The method as described in claim 2, characterized in that: The reaction temperature in the above steps is -20 degrees to 25 degrees, preferably 0 degrees.
5. The method as described in claim 2, characterized in that: The oxidant used in the above steps is selected from m-chloroperoxybenzoic acid and hydrogen peroxide, preferably m-chloroperoxybenzoic acid.
6. The method as described in claim 2, characterized in that: In the above steps, the molar ratio of the oxidant to the compound of formula I is 2 to 5:1, preferably 2:
1.
7. The method as described in claim 2, characterized in that: The reaction time for the step is 2-24 hours, preferably 6 hours.