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Production method of nifuratel

A technology of nifuratel and compound is applied in the production field of antibiotic drug nifuratel, can solve problems such as reducing production cost, environmental pollution and the like, and achieves the effects of reducing production cost, reducing cost and cheap raw materials

Active Publication Date: 2007-09-19
SUNSTONE TANGSHAN PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] The purpose of this invention is to provide a kind of new method of producing nifuratel, this method overcomes the defective that existing method exists, does not use methyl mercaptan or sodium methyl mercaptide, also does not use methyl alcohol-sodium methylate system, not only solves The problem of environmental pollution is solved, and the production cost is also greatly reduced

Method used

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  • Production method of nifuratel
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  • Production method of nifuratel

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0054] Preparation of Example 1 Intermediate 4

[0055] In a 2000mL reaction flask equipped with a high-efficiency reflux condenser and a dropping funnel, add 250g (3.125mol) of thiourea and 110mL of water, stir to partially dissolve the thiourea, stir for 10min under ice water cooling, remove the ice water, and add dropwise Dimethyl sulfate 15mL, the reaction spontaneously started under stirring, and exothermic, very violent at the beginning, after the reaction was stable, then slowly add the remaining dimethyl sulfate 155mL in the reaction bottle (about 1.5h), always Maintain a slightly boiling state, after the addition, continue to reflux for 1 hour, let it stand overnight, add 260 mL of 95% ethanol, stir for a while, cool, filter, wash twice with 95% ethanol, and dry to obtain 4364 g of product intermediates, with a yield of 84%. mp. 236°C (dec).

preparation Embodiment 2

[0056] Preparation of Example 2 Intermediate 5

[0057] In the 2000mL reaction flask, add 4139g (1.0mol), epichlorohydrin 78.5mL (92.6g, 1.0mol), benzene 500mL, 30% sodium hydroxide 500mL and catalyst tetra-n-butylammonium bromide 6.4g, under efficient stirring React at room temperature for 6 hours, separate the organic layer, extract the aqueous phase with benzene (3×200mL), combine the organic phases, wash twice with water, dry over anhydrous magnesium sulfate, evaporate benzene at normal pressure (applicable), and distill the remaining liquid under reduced pressure , to obtain 561g of a colorless and transparent liquid product intermediate, b.p.54-56°C / 20mmHg (Lit.48-52°C / 20mmHg), yield 58.7%. IR (KBr, cm -1 ), 3045, 2985, 2914, 1424, 1260; MS: 105 (M+1).

preparation Embodiment 3

[0058] Preparation Example 3 Preparation of Intermediate 6

[0059] Add 200mL of hydrazine hydrate into the reaction flask, heat to 90°C, add 588.5g (0.85mol) dropwise with stirring, and control the internal temperature at about 90°C, complete the addition in about 0.5h, and continue the reaction at 90°C for 1h. Excess hydrazine and water were removed by rotary evaporation to obtain a viscous colorless liquid. It can be directly used in the next reaction without purification, and the yield is quantitative.

[0060] If the resulting crude product is purified by vacuum distillation (a part of the product is carbonized and decomposed due to high temperature during the vacuum distillation process), a colorless, transparent and viscous pure product intermediate 6 is obtained, with a yield of 50-60%, b.p.140-146 ℃ / 2-3mmHg, it can be solidified in the refrigerator for a few days.

[0061] Preparation of Example 4 Intermediate 7

[0062] method 1:

[0063] Add 693.5g (~0.688mol), ...

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Abstract

The invention relates to a medicine producing field, specifically, to an improved producing method of antibacterial medicine nifuratel. The method makes use of thiourea as initial material to produce nifuratel. The improvement is that it is no longer to use methyl mercaptan or methomyl in the known method while producing the intermediate 2-(methylthiomethyl)hydropropane. Furthermore, the invention is no longer to use metal natrium in the known method when the 3-methylthio-2-hydroxy-propylhydrazine and diethyl carbonate are heated to produce N-amido-5-methylthiomethyl-2-oxazolidone in the existance of alkali. All of the improvements largely improve the preparation of the nifuratel, especially for the production condition in a large scale, reduce the environment pollution and benefit to ensure the production safety.

Description

technical field [0001] The invention relates to the field of medicine production, in particular, the invention relates to a production method of antibiotic nifuratel. Background technique [0002] Nifuratel (Nifuratel), its chemical name: 5-[(methylthio)methyl]-3-[[(5-nitro-2-furan)methylene]amino]-2-oxazolidine Ketone, whose English chemical name is: 5-[(Methylthio)methyl]-3-[[(5-nitro-2-furanyl)methylene]amino]-2-oxazolidinone, is a nitrofuran antibiotic drug with significant Role in the treatment of mixed vaginal infections. Its trichomonad killing activity is equivalent to metronidazole; at the same time, it has antibacterial (G+, G+) effect, and can effectively kill Chlamydia trachomatis and mycoplasma, and has certain activity against Candida; nifuratel is administered orally and vaginally It shows that it is well tolerated and has no drug resistance. The cure rate for bacterial vaginosis is equivalent to that of ampicillin and carbenicillin, and the incidence of adv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D413/12A61P31/04
Inventor 韩志强
Owner SUNSTONE TANGSHAN PHARM CO LTD
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