17 results about "Formic acid ethyl ester" patented technology

This invention discloses a method for preparing ethyl 4-pyrazolamide. A dichloromethane solution of ethyl 3-(N,N-dimethylamino)acrylate is added dropwise to a dichloromethane solution containing a chlorine-containing reagent and N,N-dimethylformamide. After addition, the mixture is stirred until the reaction is complete, yielding a reaction solution. The reaction solution is then directly added dropwise to an alcoholic solution of hydrazine hydrate, and the resulting reaction yields ethyl 4-pyrazolamide. This method uses readily available raw materials, has mild reaction conditions, high yield, and is easily industrialized.

The application discloses a preparation method of relugolix and belongs to the field of drug synthesis. The method uses 2-[(2,6-difluorobenzyl) n-propoxy amido]-4-(dimethylamino) methyl-5-(4-nitrophenyl) thiophene-3-carboxylic acid ethyl ester (formula II) as a starting material, and relugolix is prepared through the following steps: inorganic base hydrolysis, amide condensation, inorganic base cyclization, 10% Pd / C catalytic hydrogenation, and finally amide condensation with methoxyamino carbonic acid phenyl ester. The starting material used in the preparation method is cheap and easy to obtain, the reaction is mild, the operation is simple, the product has high purity and high yield, no biuret by-product is detected, and the method is suitable for industrial production.

The invention provides a method for preparing 1-methyl-3-difluoromethyl-1H-pyrazole-4-carboxylic acid with high selectivity, which comprises the following steps: reacting methylhydrazine with a protective agent in an inert solvent to obtain single-protection methylhydrazine (IV); in the presence of alkali, carrying out condensation reaction on the single protection methylhydrazine (IV) and 2-ethoxymethylene-4, 4-difluoro-3-oxobutyric acid ethyl ester (I) to obtain an intermediate (V); adding acid into the reaction system obtained in the step S2 to synchronously remove the protecting group R and form a pyrazole ring, so as to obtain 1-methyl-3-difluoromethyl-1H-pyrazole-4-ethyl formate (II); alkali is added into the 1-methyl-3-difluoromethyl-1H-pyrazole-4-ethyl formate (II) for hydrolysis, then the hydrolysis product is acidified with acid, and suction filtration is performed to obtain the 1-methyl-3-difluoromethyl-1H-pyrazole-4-carboxylic acid (III). The content of regioisomers in the prepared product is less than or equal to 1%, the HPLC purity of the product is more than or equal to 98.0%, the content of single impurities is less than or equal to 0.15%, the moisture content is less than or equal to 0.1%, the residual acid content is less than or equal to 50 ppm, and the downstream reaction requirement can be met without secondary refining.

The invention discloses a process method for synthesizing ethyl 4-bromo-5-chloro-2-ethyoxyl benzoate, and belongs to the technical field of medical intermediates. The method comprises the following steps: by taking 2-fluoro-4-bromoxynil as a raw material, firstly carrying out esterification and ethyoxyl substitution reaction on the 2-fluoro-4-bromoxynil and ethanol to generate 4-bromo-2-ethyoxyl ethyl benzoate, and then carrying out NCS chlorination reaction to generate the 4-bromo-5-chloro-2-ethyoxyl ethyl benzoate. The method has the advantages of originality, good reaction selectivity, high product purity and high yield.

The invention provides a synthesis method of 2-cyano-5-(p-tolyl)-1H-imidazole, and belongs to the field of chemical synthesis. The method comprises the following steps: by taking ethyl cyanoformate as a raw material, firstly carrying out an addition reaction and a cyclization reaction to obtain 2-carboxylic acid ethyl ester-5-(p-tolyl)-1H-imidazole, then carrying out amination and cyanation, and carrying out four-step reaction to generate the 2-cyano-5-(p-tolyl)-1H-imidazole. Compared with an existing synthesis method, a pyridine ring is innovatively constructed, the target product is synthesized under mild reaction conditions, and the synthesis method has the advantages of environmental friendliness, economical efficiency, high product yield and good industrial potential.

A preparation method of 3-iodo-1H-indole-2-carboxylic acid, which comprises the following steps: taking indole-2-carboxylic acid ethyl ester as raw material, converting into 3-formyl-1H-indole-2-carboxylic acid ethyl ester, then converting into 3-iodo-1H-indole-2-carboxylic acid ethyl ester, and finally converting into the target compound 3-iodo-1H-indole-2-carboxylic acid through an ester hydrolysis reaction. The synthesis method realizes the conversion from 3-formyl-1H-indole-2-carboxylic acid ethyl ester to 3-iodo-1H-indole-2-carboxylic acid ethyl ester in a simple method in a key step; finally, the compound 3-iodo-1H-indole-2-carboxylic acid is prepared through simple operation, low cost and relatively mild reaction conditions.

The invention discloses a preparation method of an arotinolol hydrochloride intermediate. The preparation method comprises the following steps: S1, reacting thiophene-2-carboxylic acid with an esterification reagent under the action of carbonate to obtain thiophene-2-ethyl formate; s2, enabling the thiophene-2-ethyl acetate to react with a bromination reagent, so as to obtain 5-bromothiophene-2-ethyl formate; s3, the 5-bromothiophene-2-ethyl formate and tributyl (1-ethyoxyl ethylene) tin react under the action of a catalyst, and 5-ethyoxyl vinyl-2-ethyl formate is obtained; and S4, hydrolyzing the 5-ethoxy vinyl-2-ethyl formate under an acidic condition, so as to obtain the 5-acetyl thiophene-2-formic acid. Compared with the prior art, the method has the advantages that toxic or strong corrosive reagents are not used, the total yield is high, the product purity (gt, 99.0%) is high, and the method is suitable for industrial amplification and green production.

The invention discloses a synthesis method of high-content trinexapac-ethyl. The method comprises the following steps: (1) carrying out condensation reaction on diethyl maleate and acetone to obtain 2-acetonyl-1, 4-diethyl succinate; (2) carrying out cyclization reaction on the product in the step (1) to obtain 3, 5-dioxo cyclohexyl ethyl formate sodium salt; (3) dissolving the product obtained in the step (2) with toluene, adding triethylamine, cooling to 2 DEG C after the addition is completed, then adding cyclopropylformyl chloride, transferring into a high-temperature oil bath after the addition is completed, desolventizing toluene under negative pressure at 80 DEG C, then continuously heating, and collecting fractions at 200-240 DEG C to obtain an esterified intermediate with the content of 98% or above; and (4) dissolving the product obtained in the step (3) with toluene, adding DMAP, carrying out a reaction to generate a trinexapac-ethyl toluene solution, and removing the solvent to obtain trinexapac-ethyl. According to the method, the processing steps are simplified; industrial wastewater is not generated, and the method is environment-friendly; esterification post-treatment is carried out in an original reaction kettle, and the reaction yield is high.

The invention relates to the technical field of pharmaceutical analysis, in particular to a method for detecting 2-ethyoxyl benzoyl chloride and related substances thereof, liquid chromatography is adopted for detection, and the related substances are salicylic acid, 2-ethyoxyl benzoic acid, 2-ethyoxyl methyl benzoate and 2-ethyoxyl ethyl benzoate. Chromatographic conditions comprise that octadecylsilane chemically bonded silica is used as a chromatographic column of a stationary phase; a gradient elution procedure is adopted, a mobile phase is composed of a mobile phase A and a mobile phase B, and one of water and a phosphoric acid solution is taken as the mobile phase A; one or more of acetonitrile and methanol are used as a mobile phase B; the elution gradient is 0-35 min, and the volume percentage content of the mobile phase A is 8-80%; 35-40 min, the volume percentage content of the mobile phase A is 8-15%; the volume percentage content of the mobile phase A is 8-80% in 40-41 min; the volume percentage content of the mobile phase A is 70-80% in 41-50 min. The detection method disclosed by the invention is simple and convenient to operate, the solvent is single and easy to obtain, and the method is exclusive and accurate and can be suitable for controlling the quality of the 2-ethoxybenzoyl chloride product.

The application discloses a preparation method of a monoamine oxidase B inhibitor, and comprises the following steps: 6-fluoroindole and 1-(dimethylamino)-2-nitroethylene are subjected to trifluoroacetic acid catalysis to generate 6-fluoro-3-[(E)-2-nitrovinyl]-1H-indole, and then subjected to sodium borohydride and iron powder / hydrochloric acid reduction to generate 6-fluoro-tryptamine; under an acidic condition, Pictet-Spengler reaction is carried out between 6-fluoro-tryptamine and ethyl glyoxylate to generate ethyl 7-fluoro-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-1-carboxylate and 7-fluoro-4,9-dihydro-3H-pyrido[3,4-b]indole-1-carboxylate, and then subjected to oxidative dehydrogenation aromatization reaction to generate ethyl 7-fluoro-9H-pyrido[3,4-b]indole-1-carboxylate; under the catalysis of aluminum trichloride, amine ester exchange reaction is carried out between ethyl 7-fluoro-9H-pyrido[3,4-b]indole-1-carboxylate and 3-fluorobenzylamine to generate a target compound. The method has high overall yield.

The invention provides a preparation method of 5-methoxy-2-phenoxyaniline, and belongs to the technical field of compound synthesis. The preparation method provided by the invention comprises the following steps: mixing 2-bromine-5-methoxy ethyl benzoate, phenol, first alkali, an organic solvent and a first catalyst, and carrying out a coupling reaction to obtain 2-phenoxy-5-methoxy ethyl benzoate; mixing the ethyl 2-phenoxy-5-methoxybenzoate with an alcohol solvent, a second catalyst and an ammonia source, and carrying out an amidation reaction so as to obtain 2-phenoxy-5-methoxybenzamide; and mixing the 2-phenoxy-5-methoxybenzamide with water, a second alkali and a halogenating reagent, and carrying out a Hofmann rearrangement reaction, so as to obtain the 5-methoxy-2-phenoxyaniline. According to the preparation method provided by the invention, the 5-methoxy-2-phenoxyaniline can be obtained only through three-step reaction, dangerous processes such as nitrification, diazotization and hydrogenation in a traditional preparation method are avoided, and the preparation method is safer.

The invention relates to a synthesis method of oseltamivir phosphate, which comprises the following steps: by taking (1R, 5R, 6R)-trans-5-(1-ethyl propoxy)-7-oxobicyclo [4.1. 0] hept-3-ene-3-carboxylic acid ethyl ester as a starting raw material, reacting with acetonitrile under the catalysis of indium chloride to synthesize (3aR, 4R, 7aR)-2-methyl-4-(pent-3-alcohol oxy)-3a, 4, 7, 7a-tetrahydrocyclohexene [2, 1-d] [1, 3] oxazole-6-ethyl formate; the preparation method comprises the following steps: synthesizing (3R, 4R, 5S)-4-(acetamido)-5-[(diphenylmethylene) amino]-3-(pent-3-oxyl) cyclohexene-1-ethyl formate by using ethyl acetate as a raw material, performing ring-opening reaction with benzophenonimine under the catalysis of cuprous iodide and cesium carbonate to synthesize (3R, 4R, 5S)-4-(acetamido)-5-[(diphenylmethylene) amino]-3-(pent-3-oxyl) cyclohexene-1-ethyl formate, hydrolyzing benzophenone to synthesize oseltamivir, and reacting with phosphoric acid to synthesize oseltamivir phosphate. The method has the advantages of short synthetic route, low cost, easily available initial raw materials, simple operation, few and controllable reaction impurities, and suitableness for industrial production.

The application discloses a green synthesis process of 4,6-dimethyl-2-oxo-2H-pyran-5-carboxylic acid ethyl ester, which comprises the following steps: (a) condensation reaction of ethyl acetoacetate under the action of a heterogeneous catalyst to generate a first mixture; (b) solid-liquid separation of the first mixture to obtain filtrate and residue; (c) first flash evaporation of the filtrate to obtain a first gaseous product and a first liquid product; (d) second flash evaporation of the first liquid product to obtain a second gaseous product and a second liquid product; (e) third flash evaporation of the second liquid product after impurity removal by water washing to obtain 4,6-dimethyl-2-oxo-2H-pyran-5-carboxylic acid ethyl ester product and a third gaseous product. By adopting a heterogeneous catalyst and cooperating with a multi-flash evaporation process, a double-molecule condensation reaction can occur to generate 4,6-dimethyl-2-oxo-2H-pyran-5-carboxylic acid ethyl ester.

This invention relates to a method for detecting residual formic acid in octopaine intermediates. The method involves first derivatizing the formic acid before a column, followed by detection using gas chromatography with a flame ionization detector. This method overcomes the difficulty of detecting formic acid in octopaine intermediates using ion chromatography or liquid chromatography due to their extremely poor solubility in common solvents. Furthermore, it prevents the degradation of octopaine intermediates into formic acid under high-temperature gas-phase conditions through structural modification. The substance preventing the degradation of octopaine intermediates into formic acid acts as a catalyst, catalyzing a faster and more complete reaction of formic acid and ensuring its complete conversion to ethyl formate. This improves detection efficiency while ensuring the reliability of the octopaine intermediate's quality. This method can quantitatively detect formic acid levels above 0.02% in octopaine intermediates, exhibiting high sensitivity, strong practicality, and a simple and rapid detection process.

The application discloses a preparation method of an intermediate of arolool hydrochloride, and comprises the following steps: S1, thien-2-carboxylic acid is reacted with an esterification reagent under the action of a carbonate to obtain thien-2-methyl acetate; S2, thien-2-methyl acetate is reacted with a bromination reagent to obtain 5-bromothien-2-methyl acetate; S3, 5-bromothien-2-methyl acetate is reacted with tributyl(1-ethoxyvinyl)tin under the action of a catalyst to obtain 5-ethoxyvinyl-2-methyl acetate; and S4, 5-ethoxyvinyl-2-methyl acetate is hydrolyzed under acidic conditions to obtain 5-acetylthien-2-methyl carboxylic acid. Compared with the prior art, the route avoids the use of toxic or strong corrosive reagents, has high total yield, high product purity (more than 99.0%), and is suitable for industrial amplification and green production.

The invention provides a synthesis method of febuxostat and a key intermediate, and belongs to the technical field of medicine synthesis. 4-hydroxybenzaldehyde is used as a raw material and reacts with hydroxylamine hydrochloride and sulfur in continuous flow equipment under the conditions of a photocatalyst, a solvent and illumination to obtain 4-hydroxybenzenesulfamide; the preparation method comprises the following steps: reacting 4-hydroxybenzenesulfamide with ethyl 2-chloroacetoacetate to obtain ethyl 2-(4-hydroxyphenyl)-4-methylthiazole-5-formate; the preparation method comprises the following steps: reacting 2-(4-hydroxyphenyl)-4-methylthiazole-5-ethyl formate with a cyano source under an illumination condition, so as to obtain 2-(3-cyano-4-hydroxyphenyl)-4-methylthiazole-5-ethyl formate; the preparation method comprises the following steps: carrying out etherification reaction on 2-(3-cyano-4-hydroxyphenyl)-4-methylthiazole-5-ethyl formate and bromo-iso-butane, so as to obtain the febuxostat key intermediate. The obtained febuxostat key intermediate does not need to be separated, and the febuxostat is synthesized by a two-step one-pot method.

The invention discloses application of furyl pyrrole compounds in preparation of anti-cancer drugs, and belongs to the technical field of medical chemistry. The furyl pyrrole compound disclosed by the invention is 4-[[(5-bromo furan-2-formyl) (furan-2-yl methyl) amino] methyl]-3, 5-dimethyl-1H-pyrrole-2-ethyl formate. Experiments prove that the furyl pyrrole compound 4-[[(5-bromofuran-2-formyl) (furan-2-yl methyl) amino] methyl]-3, 5-dimethyl-1H-pyrrole-2-ethyl formate shows in vitro proliferation inhibition activity to a certain degree on triple negative breast cancer, osteosarcoma and liver cancer. Wherein the compound has remarkable anti-proliferative activity on triple negative breast cancer and osteosarcoma which are clinically refractory, and a new small molecule candidate is provided for developing novel anti-tumor drugs.