Production method of nifuratel

A nifuratel and reaction technology, applied in the directions of organic chemistry, antibacterial drugs, etc., can solve problems such as reducing production costs, environmental pollution, etc., and achieve the effects of reducing production costs, reducing costs, and cheap raw materials

Active Publication Date: 2009-07-22
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

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 61 g of intermediate 5, a colorless and transparent liquid product, 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 the field of medicine production, in particular, the invention discloses an improved production method of antibiotic nifuratel. The method uses thiourea as a starting material for the preparation of nifuratel, which is improved in that the intermediate 2-(methylthiomethyl)-oxirane is no longer used in the known method. Methyl mercaptan or sodium methyl mercaptide; In addition, 3-methylthio-2-hydroxyl-propylhydrazine and diethyl carbonate are heated to react in the presence of a base for ring closure to generate N-amino-5-methylthio In the technology of methyl-2-oxazolidinone, the production method of the present invention no longer uses metal sodium commonly used in known methods. All these improvements have greatly improved the preparation of nifuratel, especially the production conditions for large-scale industrial production, reduced environmental pollution, and are conducive to ensuring safe production.

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 Patents(China)
IPC IPC(8): C07D413/12A61P31/04
Inventor 韩志强
Owner SUNSTONE TANGSHAN PHARM CO LTD
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