Oxazolidinone-based antibacterial drug preparation method

A technology of antibacterial drugs and oxazolidinone, which is applied in the field of medicine, can solve the problems of high raw material cost of catalyst palladium carbon, difficult control of metal palladium residues, and unsuitability for industrial production, and achieve high product quality, easy control of metal residues, and high yield. high rate effect

Inactive Publication Date: 2018-04-10
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] This method involves the hydrogen reduction reaction and there are certain defects. The debenzylation reaction of phosphate triester (compound of formula II) has two main by-products after liquid phase detection, and the content is about 5-10%, which may be due to incomplete debenzylation Or the ring opening of oxazolidinone, the impurity is difficult to remove after treatment, affecting the quality of the product
In addition, the raw material cost of catalyst palladium carbon is high, and the residual metal palladium in the final product is not easy to control, which is not suitable for industrial production.

Method used

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  • Oxazolidinone-based antibacterial drug preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033]

[0034] Weigh phosphate triester (compound of formula II) (10 g) into a reaction flask, add trifluoroacetic acid (100 mL) and stir to dissolve. Cool to -5°C and react at constant temperature for 3 hours, and the reaction is complete as detected by liquid chromatography. Trifluoroacetic acid was distilled off, N,N-dimethylformamide was dissolved, concentrated under reduced pressure until solids were precipitated, and dried to obtain 6.73 g of compound I with a yield of 93% and a liquid phase purity of 99.4%.

[0035] 1 H NMR ((CD 3 ) 2 SO, 500MHz) δ: 2.82(s, 3H), 3.70~3.72(m, 1H), 3.97(t, J=8.8Hz, 1H), 4.11~4.22(m, 4H), 4.64~4.69(m, 2H ), 5.63(dd, J=9.0, 6.0Hz, 1H), 7.41~7.42(m, 2H), 7.55(d, J=8.4Hz, 1H), 7.98(d, J=9.0Hz, 1H), 8.15 (dd, J=8.4, 2.2Hz, 1H), 8.93(d, J=2.2Hz, 1H);

[0036] ESI-MS m / z: 478.1{[M+H] +}.

Embodiment 2

[0038]

[0039] Weigh phosphate triester II (10 g) into a reaction flask, add trifluoroacetic acid (30 mL) and dichloromethane (100 mL) and stir to dissolve. React at room temperature for 2 hours, and the liquid chromatography detects that the reaction is complete. The solvent was evaporated, N, N-dimethylformamide was dissolved, concentrated under reduced pressure until a solid precipitated, and dried to obtain 6.88 g of compound I, with a yield of 95% and a liquid phase purity of 99.7%.

Embodiment 3

[0041]

[0042] Weigh phosphate triester II (10 g) into a reaction flask, add 27% hydrochloric acid isopropanol solution (100 mL) and stir to dissolve. React at room temperature for 2 hours, and the liquid chromatography detects that the reaction is complete. The solvent was evaporated, N, N-dimethylformamide was dissolved, concentrated under reduced pressure until a solid precipitated, and dried to obtain 6.35 g of compound I with a yield of 87% and a liquid phase purity of 98.1%.

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Abstract

The invention discloses a method for preparing an oxazolidinone-based antibacterial drug through acid catalyzed debenzylation, and belongs to the field of medicine and chemical industry. According tothe present invention, a compound represented by a formula II is subjected to debenzylation under the action of an acid catalyst to obtain a compound represented by a formula I; and the method has advantages of inexpensive and easily-available raw material, safe and simple operation, environmental protection technology, high product quality, high yield and easily-controlled metal residue in the product, and is suitable for commercial production.

Description

technical field [0001] The invention relates to a preparation method of oxazolidinone antibacterial drugs, which belongs to the field of medicine. Background technique [0002] Bacteria can mutate and acquire drug resistance when exposed to antibacterial drugs, and the abuse of antibiotics by humans has exacerbated the development of drug-resistant bacteria, and the antibacterial effect of antibiotics has continued to decline, seriously threatening human health. In the "post-antibiotic era", countries have realized the importance of developing new antibacterial drugs. The United States approved the "FDA Safety and Innovation Act" in 2012, the eighth part of which is the "Encouraging Development of Antibiotics Act" (GAIN Act). [0003] Since the beginning of the new century, new oxazolidinone antibacterial drugs have been gradually developed, such as Linezolid developed by Pharmacia Upjohn in the United States. This drug was approved by the FDA in 2000. The world's first mar...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/6561
CPCC07F9/6561
Inventor 赵胜贤祝方猛赵能选叶素斌储结根石俞强杜江伟常明亮叶月飞
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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