20 results about "Ethyl cyanoacetate" patented technology

The invention relates to the technical field of organic synthesis, in particular to a preparation method of 1, 1-cyclohexyl diacetic acid. The preparation method comprises the following steps: taking cyclohexanone and ethyl cyanoacetate as raw materials to react and dehydrate to prepare a product 1, then reacting cyanoacetamide, sodium methoxide and the product 1 at low temperature to obtain a product 2, and then hydrolyzing the product 2 under the catalysis of a magnetic solid double-acid catalyst to obtain the 1, 1-cyclohexyl diacetic acid. The used magnetic solid double-acid catalyst is prepared by loading a metal active layer and a sulfonic acid group on a magnetic mesoporous silicon dioxide carrier step by step, and has Lewis acid and Bronsted acid sites, and the catalyst is separated by an external magnetic field after the reaction. The method is short in reaction time and high in catalytic efficiency, the catalyst can be recycled, the separation problem of traditional homogeneous acid catalysis is avoided, and the method has the advantages of being mild in reaction condition, high in yield, environmentally friendly and the like and is suitable for industrial production of 1, 1-cyclohexyl diacetic acid.

The present application relates to a kind of five-ring thiazole indole ketone piperazine amide derivatives and purposes thereof.The derivatives take ethyl cyanoacetate as starting material, generate hydroxylamine compound (A) under the action of sodium nitrite and phosphoric acid;Obtain 2-amino ethyl cyanoacetate (B) by reduction, in turn with acetic anhydride, lawson reagent is reacted, and 5-amino-4-carboxylate thiazole compound (D) is obtained;After bromination by NBS, under the catalysis of phosphorus oxychloride, react with tetrahydropyridine indole ketone, generate 2-bromo-6,7-dihydrothiazolo [5'',4'':4',5'] pyrimido [1',2':1,2] pyrindo [3,4-b] indole-4 (12H) -ketone (F), again under alkaline condition, first with Boc piperazine, then by Boc treatment and obtain compound (H);Finally, react with acyl chloride, and 28 different substitution structures of five-ring thiazole indole ketone piperazine amide compound (I1-I28) are synthesized.The 28 compounds are tested on three kinds of cancer cells, and the results show that: 28 compounds have significant inhibitory activity on Hela cervical cancer cells, HT-29 human colon cancer cells and HGC-27 human gastric cancer cells.

The invention belongs to the technical field of medicine detection, and particularly relates to a GCMS (Gas Chromatography Mass Spectrometry) detection method for ethyl cyanoacetate in tofacitinib citrate. Respectively injecting the blank solution, the reference solution and the test solution into a GCMS (Gas Chromatography Mass Spectrometer), recording a spectrogram, and calculating the content of ethyl cyanoacetate in tofacitinib citrate by adopting an external standard method; wherein the GCMS conditions comprise a chromatographic column, the column temperature of the chromatographic column is kept at 40 DEG C for 1 min, the temperature is increased to 240 DEG C at the heating rate of 15 DEG C / min, and the temperature is kept for 1 min. The method can accurately and quantitatively detect the content of ethyl cyanoacetate in tofacitinib citrate, and is simple to operate, high in precision, good in stability and good in reproducibility.

The application discloses a processing technology of ethyl dicyanopropionate, and comprises the following specific steps: S1, preparing raw materials, storing liquid raw materials uniformly for standby, and placing solid raw material ethyl cyanoacetate in a humid environment with certain humidity to make it lump; S2, pre-treating the lumped ethyl cyanoacetate by using a pre-treatment device, and then crushing the lumped ethyl cyanoacetate after component separation; S3, mixing the ethyl cyanoacetate with a potassium cyanide solution, and then slowly adding a formaldehyde solution into the mixture for reaction; S4, separating the organic layer from the reaction liquid, extracting the water layer by using a solvent dimethyl sulfoxide, mixing the organic layers, and finally obtaining ethyl dicyanopropionate finished products after drying and desolventizing; in the step S2, the pre-treatment device comprises a storage mechanism, a high-frequency vibration device and an ejection mechanism; the processing technology of ethyl dicyanopropionate disclosed by the application has the effect of reducing the exposure amount of dust, thereby providing effective protection for the personal safety of workers.

The invention relates to a method for efficiently preparing flurbiprofen based on a Suzuki-Miyaura coupling reaction. The preparation method comprises the following steps: taking ethyl cyanoacetate as a raw material, and carrying out methylation reaction on the ethyl cyanoacetate and methyl iodide or dimethyl sulfate to prepare racemic ethyl 2-cyanopropionate; the racemic ethyl 2-cyanopropionate and 4-bromine-2-fluorobiphenyl are subjected to a similar Suzuki-Miyaura reaction under the combined action of a zero-valent palladium metal catalyst, a metal stabilizer phosphine ligand and alkali, and the racemic ethyl 2-cyano-2-(2-fluoro4-biphenyl) propionate is obtained; and carrying out hydrolysis and decarboxylation on the racemic 2-cyano-2-(2-fluoro-4-biphenyl) ethyl propionate to obtain racemic 2-(2-fluoro-4-biphenyl) propionic acid, namely, the flurbiprofen. The process route comprises three steps of reaction, materials are cheap and easy to obtain, operation is simple, aftertreatment is convenient, and the obtained product is high in purity.

The invention discloses an energetic compound based on pyrazolo [1, 5-a] pyrimidine and a synthesis method of the energetic compound. The synthesis method comprises the following steps: (1) reacting 2-oxime ethyl cyanoacetate, potassium permanganate and potassium hydroxide to prepare potassium salt of 2-cyano-2-nitroethyl acetate; (2) enabling the potassium salt of the 2-cyano-2-nitroethyl acetate to react with hydrazine hydrate, so as to prepare 5-amino-4-nitro-1, 2-dihydro-3-pyrazolone; and (3) carrying out a reaction on the 5-amino-4-nitro-1, 2-dihydro-3-pyrazolone, potassium permanganate and potassium hydroxide, so as to prepare the potassium salt of the 5-hydroxy-3, 6-dinitropyrazolo [1, 5-a] pyrimidine-2, 7 (1H, 4H)-diketone. The synthesis process is mild in condition and high in safety, the raw materials are easy to prepare, the product yield is high, and the synthesized energetic compound has good detonation performance and low sensitivity and has potential application value in the field of energetic materials.

The application discloses a coumarin and thiouracil ester derivative, and a synthesis method thereof. The chemical general formula is shown as formula I, wherein R1 is hydrogen, an alkyl group, halogen or a phenyl group; R2 is hydrogen or halogen; and R3 is hydrogen or halogen. The method comprises the following steps: taking phenyldiol 1 and methyl acetoacetate 2 as raw materials, reacting in sulfuric acid under normal temperature conditions to obtain an intermediate 3, further reacting the intermediate 3 with p-chloromethyl benzoyl chloride to obtain a compound 5, refluxing aromatic aldehyde 6, ethyl cyanoacetate 7 and thiourea 8 in ethanol to obtain an intermediate product 9, and refluxing the compound 5 and 9 in acetonitrile under the catalysis of potassium carbonate to synthesize a target product I. The method is simple, easy to operate and easy to scale up, and the prepared compound I has strong bacteriostatic activity, and can be widely applied in bacteriostatic drug preparations.

The invention discloses a method for preparing a niraparib chiral intermediate by a chemical-enzyme method. According to the method disclosed by the invention, a compound II is taken as an initial raw material and firstly reacts with ethyl cyanoacetate to obtain a compound III, the compound III is subjected to Michael addition and decarboxylation ring closing reaction to obtain a compound V, the compound V is converted into a compound VI under the action of hydantoinase, and finally the niraparib chiral intermediate I is obtained through amide reduction, acid amine condensation and lactam reduction reaction. The route is simple to operate and low in cost, and can be used for industrial production.

The application discloses a method for synthesizing imidazo[1,2-alpha]pyridine derivatives by using dichlorotitanocene as a Lewis acid catalyst. In the method, 2-amino pyridine compounds, benzaldehyde compounds and ethyl isocyanoacetate are used to react at 40-60 DEG C by using a one-pot method without a solvent. The 2-amino pyridine compounds and the benzaldehyde compounds are used to react to generate an imine intermediate under the catalysis of the dichlorotitanocene. The imine intermediate is used to add with the ethyl isocyanoacetate to generate a subsequent intermediate. The imidazo[1,2-alpha]pyridine derivatives are generated by a [4+1] cycloaddition reaction and a 1,3 proton transfer. The method has the advantages of simple operation, low synthesis cost, mild reaction condition, short reaction time, green and solvent-free catalysis, and the like. After the reaction is completed, the product can be separated only by simple column chromatography.

This invention provides a regrugoline intermediate and its preparation method, belonging to the field of pharmaceutical synthesis technology. The preparation method of the regrugoline intermediate specifically includes the following steps: (1) reacting p-bromophenylacetic acid with a catalyst and acetic anhydride and acetic acid to generate compound A; (2) reacting compound A with ethyl cyanoacetate and elemental sulfur under the action of a base to generate compound B; (3) reacting compound B with isobutyl chloroformate to generate compound C; (4) reacting compound C with 2,6-difluorobenzyl chloride under the action of a base to generate compound D; (5) reacting compound D with N-methoxyurea under the action of palladium, a ligand, and a base to generate compound E. This invention features mild reaction conditions, high reaction yield, strong operability, low production cost, and is environmentally friendly, making it suitable for large-scale industrial production.

The invention relates to a tricyclic thiazolo [5, 4-d] pyrimidone amine derivative and application thereof.The preparation method comprises the steps that ethyl cyanoacetate serves as a raw material, a hydroxylamine compound (A) is generated under the action of sodium nitrite and phosphoric acid, 2-amino ethyl cyanoacetate (B) is obtained through reduction, the 2-amino ethyl cyanoacetate (B) is subjected to a reaction with acetic anhydride and Lawson to obtain a 5-amino-4-formate thiazole compound (D), and the 5-amino-4-formate thiazole compound (D) is subjected to a reaction with acetic anhydride and Lawson to obtain the tricyclic thiazolo [5, 4-d] pyrimidone amine derivative. The preparation method comprises the following steps: under the action of phosphorus oxychloride, obtaining a 2-bromo-pyrroline [1, 2-a] thiazolo [5, 4-d] pyrimidinone compound (F), a 2-bromine-7, 8-dihydro-5H-pyridine [1, 2-a] thiazolo [5, 4-d] pyrimidine-10 (6H) ketone derivative (G) and a 2-bromine-6, 7, 8, 9-tetrahydrothiazolo [5 ', 4': 4, 5] pyrimidino [1, 2-a] azepine-11 (5H)-ketone (H); 36 different substituted tricyclic thiazolopyrimidinone amine compounds F1-F12, G1-G12 and H1-H12 are obtained under the action of alkali, and the inhibitory activity of the 36 compounds on cancer cells is investigated.

This invention discloses a method for preparing 3-chloro-1H-pyrazole-5-amine. The target product is prepared via a three-step reaction involving cyclization, chlorination, and decarboxylation, starting with ethyl ethoxymethylene cyanoacetate. Hydrazine hydrate is used for cyclization, dichlorohydantoin for chlorination, and dilute sulfuric acid for decarboxylation. This process is mild, simple to operate, highly safe, and requires minimal equipment, making it suitable for large-scale production. The yield of compound III is up to 61.6%, compound IV to 44.2%, and compound I to 64%. The purity of all products, as determined by HPLC, reaches 99%, effectively improving production efficiency.

This invention discloses a method for synthesizing an intermediate of ennadustat, belonging to the pharmaceutical field. The method uses ethyl cyanoacetate and benzaldehyde as starting materials, undergoing a Knevengel condensation reaction, followed by reduction to obtain compound 4. Compound 4 undergoes nucleophilic substitution with compound 5 to obtain compound 6. Compound 6 is then hydrolyzed and decarboxylated to obtain the key intermediate compound 7. This invention uses inexpensive and readily available ethyl cyanoacetate and benzaldehyde as starting materials, and successfully constructs the key intermediate of ennadustat through a tandem process of Knevengel condensation, Hans ester reduction, nucleophilic substitution, and hydrolysis decarboxylation. The entire process avoids the use of expensive palladium catalysts, fundamentally solving the problem of heavy metal residues. Furthermore, the reaction conditions are mild, the operation is simple, the yield is greatly improved, the product purity is high, and the reduced cost makes it more suitable for industrial production.

The scheme discloses a series of corrole derivatives in the field of pharmaceutical chemistry and a preparation method and application thereof, and the structural general formula of the corrole derivatives is shown as formula (I) or formula (II) or formula (III) in the text. The fluorescent compound of the application adopts a typical corrole intermediate, takes malonitrile or ethyl cyanoacetate as an electron acceptor, and introduces an active electron-donating group to form a conjugated system of push-pull electrons. The structural system after the cyclization of ethyl cyanoacetate creates more additional regions, and provides feasibility for the construction of new structures. Most of the compounds show good binding affinity to Aβ 42 aggregates, and the low cytotoxicity is verified, and the aggregates can be successfully used for the imaging of Aβ in vivo and in vitro.

The invention provides 2, 6-dichloro-3-cyano-4-methylpyridine and a preparation method thereof, and relates to the technical field of preparation of intermediates. The preparation method comprises the following steps: S1, carrying out condensation reaction on acetoacetamide and ethyl cyanoacetate in an organic solvent I by taking carbonate as a catalyst to evaporate out a byproduct ethanol, adding a water absorbent, and carrying out cyclization reaction to prepare 2, 6-dihydroxy-3-cyano-4-methylpyridine; s2, the 2, 6-dyhydroxyl-3-cyano-4-methylpyridine prepared in the step S1 is subjected to a chlorination reaction in an organic solvent II under the action of 4-dimethylaminopyridine and phosphorus pentachloride, and the 2, 6-dichloro-3-cyano-4-methylpyridine is prepared. According to the preparation method of the 2, 6-dichloro-3-cyano-4-methylpyridine, provided by the invention, the cost is effectively reduced, the environmental pollution is reduced, and the production efficiency and the product quality are also effectively improved.

The invention belongs to the technical field of chemical synthesis of medicines, and particularly relates to a synthesis method of an LXH-1211 intermediate. The preparation method comprises the following steps: carrying out stirring reaction on phenylhydrazine, 3-aminocrotonitrile and a reaction solvent to obtain an intermediate IM-1; mixing the intermediate IM-1 and a reaction solvent, cooling, adding phosphorus oxychloride, and heating for reaction to obtain an intermediate IM-2; and dissolving the intermediate IM-2 in a reaction solvent, adding ethyl cyanoacetate, and carrying out a stirring reaction to obtain the LXH-1211 intermediate. The raw materials are easy to obtain, use of highly toxic and explosive materials, column chromatography and other operations are avoided, the yield is remarkably improved, special equipment is not needed, industrial amplification is facilitated, and the environmental protection cost is effectively reduced.

The invention relates to the field of pharmaceutical analytical chemistry, and provides a method for detecting N, N '-diisopropyl carbodiimide and / or 2-oxime ethyl cyanoacetate in polypeptide, which comprises the following steps: 1) preparing an N, N'-diisopropyl carbodiimide and / or 2-oxime ethyl cyanoacetate reference substance solution by using a diluent; 2) dissolving the polypeptide by using the diluent to prepare a test solution; (3) detecting the reference substance solution and the test solution by using a liquid chromatography; wherein the chromatographic conditions are as follows: a chromatographic column is a liquid chromatographic column taking adamantyl bonded silica gel as a stationary phase; the detector is an ultraviolet detector; a mobile phase A is 0.05% (v / v) trifluoroacetic acid aqueous solution, and a mobile phase B is acetonitrile. The method is simple and convenient, low in cost, good in system applicability, high in specificity, high in sensitivity, good in recovery rate and high in accuracy, and N, N '-diisopropylcarbodiimide and 2-oxime ethyl cyanoacetate can be detected at the same time.

The invention relates to the technical field of medical instrument detection, in particular to a method for determining the content of impurities in a medical adhesive through gas chromatography. According to the characteristics of two impurity compounds of ethyl cyanoacetate and butyl cyanoacetate, the gas chromatograph is selected, instrument parameters and sample pretreatment conditions are optimized, and the impurity content in the medical adhesive can be accurately determined.

The invention relates to the technical field of preparation of etocrilene, and discloses a preparation method of etocrilene, which sequentially comprises the steps of condensation reaction, rough preparation, refining, drying and packaging. According to the preparation method of the etocrilene provided by the invention, the vacuum degree and the temperature are synergistically optimized, and the reaction time is shortened and the generation of by-products is inhibited mainly by applying the vacuum degree of-0.088 MPa, controlling the temperature in stages, reducing the reaction activation energy and promoting the full contact of ethyl cyanoacetate and benzophenone. The vacuum environment can timely remove moisture generated by the reaction and push the balance to move towards the positive reaction direction, so that the yield is obviously improved. By optimizing the raw material ratio, the nucleophilic activity of benzophenone can be enhanced by a composite catalytic system of acetic acid and ammonium acetate, so that the raw material conversion rate is greatly improved compared with that of a traditional process. Through the synergistic effect of the processes of all the steps, the problems of low purity and insufficient yield in the prior art are systematically solved.