4936-47-4

Usage

Uses

Used in Pharmaceutical Industry:
Nifuratel is used as an antibacterial agent for treating various bacterial infections, particularly those caused by gram-positive and gram-negative bacteria. Its broad-spectrum action makes it a versatile choice in the treatment of different types of infections.
Used in Antifungal Applications:
Nifuratel is used as an antifungal agent, effective against fungal infections caused by Candida spp. Its potent action helps in controlling and eliminating fungal pathogens, contributing to the management of various fungal conditions.
Used in Antiprotozoal Treatment:
Nifuratel is used as an antiprotozoal agent, particularly effective against Trichomonas infections. It plays a significant role in the treatment of trichomoniasis, a sexually transmitted infection caused by the protozoan parasite Trichomonas vaginalis.
Used in Gynecological Infections:
Nifuratel is used as a treatment for common gynecological infections, including those caused by chlamydia and mycoplasma. Its broad-spectrum antimicrobial effect makes it a valuable asset in the management of various gynecological conditions.
Brand Names:
Some of the brand names under which Nifuratel is marketed include Macmiror, Magmilor, Polmiror, and Tydantil, all manufactured by Polichimica Sap, Italy.

Originator

Macmiror,Poli,Italy,1965

Clinical Use

Nifuratel indications include:1.bacterial vaginosis, trichomonas vaginitis, vulvovaginal candidiasis, vaginal mixed infections.2.urinary tract infections.3.gastrointestinal amoebiasis and trichomoniasis Jia.

Synthesis

The synthesis of Nifuratel is as follows:Add 450ml of ethanol, 450ml of water, and 50ml of phosphoric acid into the reaction flask, then add 5-nitrofuraldehyde diacetate 267.5 (1.1mol), reflux for 0.5-1h, and naturally cool to room temperature to obtain a 5-nitrofurfural solution. Under dark conditions, add N-amino-5-methylthiomethyl-2-oxazolidinone dropwise to the 5-nitrofurfural solution, stir and react at room temperature for 2 to 3 hours, stand still for crystallization, filter and filtered cake was washed with absolute ethanol solvent (60ml×3) and dried to obtain crude nifuratel. Under dark conditions, take the crude Nifuratel and add 10 times the volume of glacial acetic acid, heat to boil, add activated carbon, filter while hot, the filtrate is allowed to stand for crystallization and filtration, the filter cake is washed with ethanol (60ml×3), nifuratel pure product (197.7g, yield 99.93%, purity 99.93%).

InChI:InChI=1/C10H11N3O5S/c1-19-6-8-5-12(10(14)18-8)11-4-7-2-3-9(17-7)13(15)16/h2-4,8H,5-6H2,1H3/b11-4-

Synthetic route

5-nitrofurane-2-carboxaldehyde (698-63-5) + 3-amino-5-[(methylthio)methyl]oxazolidin-2-one (25517-72-0) → nifuratel (4936-47-4)

Conditions	Yield
at 15 - 40℃; for 5h; Temperature; Large scale;	96.9%
In ethanol; water at 20℃; Darkness;	197.7 g

Upstream product

• 698-63-5 5-nitrofurane-2-carboxaldehyde 
• 25517-72-0 3-amino-5-[(methylthio)methyl]oxazolidin-2-one 
• 92-55-7 5-nitro-2-furfuraldehyde diacetate 

Relevant academic research and scientific papers

Industrial preparation method of nifuratel

The invention provides a preparation method of nifuratel. The preparation method comprises the following steps: (1) reacting sodium methyl mercaptide with epoxy chloropropane to prepare 2-(methylthiomethyl)-oxetane; (2) dropwise adding the 2-(methylthiomethyl)-oxygen heterocyclic propane into hydrazine hydrate, so as to prepare 3-methylthio-2-hydroxyl-propyl hydrazine; (3) adding diethyl carbonate into the 3-(methylthio-2-hydroxy)-propyl hydrazine, so as to prepare N-amino-5-(methylthiomethyl)-2-oxazolidinone; and (4) hydrolyzing the 5-nitrofuran formaldehyde diacetate in the presence of dilute acid to obtain a 5-nitrofurfural solution; under a dark condition, adding the prepared N-amino-5-methylthiomethyl-2-oxazolidinone into a 5-nitrofurfural solution, reacting at room temperature to obtain a nifuratel crude product, and recrystallizing and purifying to obtain a nifuratel pure product.

Preparation method of nifuratel

The invention relates to a preparation method of nifuratel. The method comprises the following steps: (1) reacting a compound 1 (with the chemical name of epichlorohydrin) with a compound 10 (with thechemical name of tert-butyl hydrazinoformate) to obtain an intermediate 11, (2) reacting the intermediate 11 with CDI (with the chemical name of carbonyl diimidazole) to obtain an intermediate 12, (3) carrying out substitution reaction on the compound 12 and sodium methyl mercaptide to obtain an intermediate 13, (4) under the action of acid, removing Boc groups in the structure of the intermediate 13 are removed, so that an intermediate 4 is obtained, and (5) reacting the intermediate 4 with 5-nitrofurfural to obtain nifuratel. The process route provided by the invention has the advantages ofshort route, cheap and easily available raw materials, simplicity and convenience in operation, high reaction yield, avoidance of production of low-boiling-point sulfur-containing intermediates, environmental friendliness and easiness in industrial production.

Preparation process of anti-infective drug nifuratel

The invention belongs to the technical field of drug synthesis and in particular relates to a preparation process of an anti-infective drug nifuratel. The preparation process comprises the following steps: taking iodomethane, sodium sulfide and chlorocyclopropane as initial raw materials to obtain epoxy propyl methyl sulfide, carrying out ring-opening reaction with hydrazine hydrate to obtain 3-methylmercapto-2-hydroxyl-propylhydrazine, carrying out a ring-closure reaction to obtain N-amino-5-methylthiomethyl-2-oxazolidinone, hydrolyzing 5-nitro furfural diacetate in the presence of trifluoroacetic acid to obtain 5-nitro-2-furancarboxaldehyde, and performing condensation with N-amino-5-methylthiomethyl-2-oxazolidinone, thereby obtaining the nifuratel. Safe and cheap reagents are selected in the process route, and environment hazards are reduced. Meanwhile, the operating difficulty and reaction after-treatment burdens are reduced, the production safety is ensured, the process is a simple, green and economic process route for preparing the nifuratel, and the obtained product is high in yield, excellent in purity and suitable for large-scale industrial production of the nifuratel.

Process for removing nifuratel cyclization impurities

The invention relates to nifuratel, in particular to a process for removing nifuratel cyclization impurities. The process for removing the nifuratel cyclization impurities comprises the step of preparing a hydrazinolysis product, namely 3-methyl thio-2-hydroxyl-propyl hydrazine and is characterized in that the 3-methyl thio-2-hydroxyl-propyl hydrazine, diethyl carbonate and sodium methoxide are mixed, then cyclized and filtered to obtain cyclization mother liquor, and the cyclization mother liquor is subjected to adsorption treatment through a macro-porous resin packing column, then is condensed with 5-nitro furfural and is re-crystallized to obtain nifuratel. The process provided by the invention has the beneficial effects that through performing treatment on the cyclization mother liquorthrough the macro-porous resin packing column, a cyclized product is completely separated from cyclized impurities and other impurities. The invention overcomes the defect that an existing process cannot completely remove the cyclized impurities and the other impurities and finds a simple, effective, safe and environment-friendly method suitable for industrialization.

A synthetic method of Nifuratel (by machine translation)

The invention discloses a method for synthesizing Nifuratel. The method of the invention is sodium methyl mercaptan, ech in catalyst-tetrabutyl ammonium bromide under the effect of the compound into a sulfur [...] propane, resulting a sulfur [...] propane and hydrazine reflux 1 - 3 hours to be hydrazinolysis, to obtain 3 - methylthio - 2 - hydroxy [...]; and the resulting reaction mixture in sodium methoxide under the action of the cyclization, shall be N - amino - 5 - methylthio methyl - 2 - oxazolidone, the resulting product with the 5 - nitro furfural b ethyl ester in dilute mineral acid conditions condensation, get the yellow powder 5 - [(methylthio) methyl] - 3 - [[ (5 - nitro - 2 - furyl methylene] amino] - 2 - oxazolidone. This invention lies in the use of its primary product with the raw material of the nature of the nature of the difference between the direct chemical combination, without rectification and purification, overcomes the tedious operation in production steps, simplifies the synthesis method, convenient for large-scale industrial production. (by machine translation)

Nifuratel preparation method

The invention belongs to the technical field of synthesis of medicines and particularly relates to a nifuratel preparation method. The nifuratel preparation method comprises the following steps: taking epoxy propyl dimethyl sulfide as the starting material, having a ring-opening reaction with tert-butyl carbazate to obtain N'-(2-hydroxyl-3-methylmercapto-propyl)-tert-butyl carbazate; having a ringclosing reaction with urea under the catalytic action of cuprous bromide, obtaining a key intermediate N-(Boc-amino)-5-methylmercapto-methyl-2-oxazolidinone; hydrolyzing 5-nitro furfural diacetate under the action of trifluoroacetic acid to obtain 5-nitrofurfural, condensing with N-(Boc-amino)-5-methylmercapto-methyl-2-oxazolidinone, and obtaining nifuratel. In the process route, the cheap easy-to-get agents are chose, the operation difficulty and the processing burden caused after the reaction are reduced, the environmental harm is reduced, the production safety is guaranteed, and the preparation method is an easy, green and economical process route for the preparation of the nifuratel.

As shown in a formula E micromolecule method for the preparation of the compounds of

The invention discloses a preparation method of a compound nifuratel as shown in the formula E. purity of the compound nifuratel product as shown in the formula E reaches more than 99.97%; postprocessing yield reaches more than 96%; and total yield reaches more than 104%. The preparation method is simple and easy to control. Postprocessing operation is convenient and easy to implement. The preparation method is more beneficial to large-scale industrial production and application. Raw materials used in the invention are greatly supplied at home and are cheap in price. Thus, environmental pollution is further minimized.

Method for preparing 5-nitro-2-furaldehyde and nifuratel

The invention discloses a method for preparing 5-nitro-2-furaldehyde. The method comprises the following steps: a) 5-nitryl furfural ester diacetate, low alcohol, inorganic acid, lewis acid or a mixture of the above components are subjected to a reaction for 1-2 hours at the temperature of 70-90 DEG C to obtain a reaction solution containing 5-nitro-2-furaldehyde; b) removing low alcohol from the reaction solution in the step a) through vacuum concentration to obtain a concentrate; dissolving the concentrate by dichloromethane, washing the concentrate, drying the concentrate, performing vacuum concentration to obtain a crude product; and c) purifying the crude product in the step b) through silica-gel column chromatography to obtain 5-nitro-2-furaldehyde. The method has the advantages of less side reaction and short reaction time, and can increase the yield and purity of the 5-nitro-2-furaldehyde. The prepared 5-nitro-2-furaldehyde has the advantages that impurity is little, purifying treatment is not required, the 5-nitro-2-furaldehyde can be directly used for preparing nifuratel, preparation operation steps of nifuratel are simplified, and the yield and the purity of nifuratel are increased.

Nifuratel method for the preparation of

The invention relates to a method for preparing nifuratel. The method comprises the steps of (1) synthesizing 2-(methylmercapto-methyl)-oxacyclopropane through epoxy chloropropane and sodium methyl mercaptide; (2) generating reaction between hydrazine hydrate and the 2-(methylmercapto-methyl)-oxacyclopropane to synthesize 3-methylmercapto-2-hydroxy-propyl hydrazine; (3) generating reaction between diethyl carbonate and 3-methylmercapto-2-hydroxy-propyl hydrazine to prepare N-amino-5-methylmercapto-methyl-2-oxazolidinone; (4) hydrolyzing 5-nitrofuran formaldehyde diacetate ester under an acidic condition to prepare 5-nitro-2-furaldehyde; (5) generating reaction between the 5-nitro-2-furaldehyde and the N-amino-5-methylmercapto-methyl-2-oxazolidinone obtained in the step (3) to obtain the nifuratel, wherein in the step (1), 15-crown ether-5 is used as a catalyst, so that the conversion rate is high; no organic solvent is used during posttreatment of a product, and the posttreatment is simple.

A method for synthesizing micromolecule

The invention discloses a synthetic method of nifuratel. The synthetic method comprises the steps of carrying out a substitution reaction between epoxy chloropropane and sodium methyl mercaptide in the presence of a phase transfer catalyst to obtain epoxy propyl dimethyl sulfide, and then performing hydrazinolysis, cyclization and condensation on the obtained epoxy propyl dimethyl sulfide to obtain the nifuratel. The synthetic method is high in nifuratel yield, high in purity and low in impurity content; besides the method has the advantages that a ring-closure reaction is carried out under the alkaline condition of sodium methoxide, the use of metal sodium is avoided, production safety is ensured, and simultaneously, the reaction is easy to arouse, easy to control in process, the used raw materials are easy to get, basically no waste liquid is generated in the reaction of each step, and therefore, industrial pollution is greatly reduced; and as a result, the synthetic method of nifuratel is applicable to industrial production.