25517-72-0Relevant academic research and scientific papers
Preparation method of nifuratel
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Paragraph 0072-0084, (2021/03/10)
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 method of nifuratel intermediate
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Paragraph 0029; 0034-0035; 0038; 0043-0044; 0048; 0053-0054, (2021/05/01)
The invention provides a preparation method of a nifuratel intermediate. The preparation method comprises the following steps: (1) reacting sodium methyl mercaptide with epoxy chloropropane to prepare 2-(methylthio methyl)-oxetane; (2) dropwise adding 2-(methylthio methyl)-oxetane into hydrazine hydrate to prepare 3-methylthio-2-hydroxy-propyl hydrazine; (3) adding diethyl carbonate into 3-methylthio-2-hydroxy-propyl hydrazine to prepare a nifuratel intermediate, namely N-amino-5-methylthio methyl-2-oxazolidinone; and (4) salifying the prepared N-amino-5-methylthio methyl-2-oxazolidinone and concentrated hydrochloric acid to prepare the nifuratel intermediate hydrochloride. According to the preparation method of the nifuratel intermediate, disclosed by the invention, the nifuratel intermediate can be conveniently and quickly obtained, and the obtained nifuratel intermediate is high in yield, high in purity and stable in quality.
Industrial preparation method of nifuratel
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Paragraph 0031-0084, (2021/05/05)
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 process of anti-infective drug nifuratel
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Paragraph 0024; 0060-0065, (2018/05/16)
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
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Paragraph 0031; 0035; 0036; 0041; 0046, (2018/09/11)
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.
Preparation method of high-purity nifuratel intermediate
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Paragraph 0017; 0031-0035, (2017/10/07)
The invention provides a preparation method of a nifuratel intermediate 3-amino-5-[(methylthio) methyl] oxazoline-2-ketamine hydrochloride, which is high in yield, high in purity and suitable for industrial production. The method comprises the steps of taking1-hydrazino-3-methylmercapto-2-propyl alcohol and diethyl carbonate as raw materials and generating a compound 1 under sodium methoxide catalysis; and obtaining high-purity target product intermediate through after-treatment steps (vacuum concentration, solvent addition and dissolution, pH value adjustment, filtration, salt formation and beating). A nifuratel crude product generated through condensation of the intermediate and 5-nitro-2-furaldehyde is qualified in complete inspection without refining, and the purity can reach 99.9% or above.
As shown in a formula E micromolecule method for the preparation of the compounds of
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Paragraph 0067; 0068; 0069; 0070, (2016/12/01)
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.
A method for synthesizing micromolecule
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Paragraph 0046, (2016/12/01)
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.
Nifuratel method for the preparation of
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Paragraph 0048, (2016/12/01)
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.
