228 results about "Ethyl cyanoacetate" patented technology

The invention discloses a novel method used for preparing high-purity 4-chloropyrrolo[2,3-d]pyrimidine in industrialization scale. According to the method, ethyl cyanoacetate, bromo-acetal, formamidine acetate, and sodium alcoholate are taken as raw materials; N,N-dimethylformamide, ethyl alcohol, and phosphorus oxychloride are taken as solvents; and 4-chloropyrrolo[2,3-d]pyrimidine is obtained via three-step approach. The process route of the method is simple; time is short; next step feed can be carried out directly without complex purification process of intermediates; no toxic agent is used; the method is safe and reliable, and is low in cost; total yield is higher than 30%; and the purity of obtained products is as high as 99.2%.

The invention relates to a preparation method of 4-chloropyrrolo[2,3-d]pyrimidine.The method includes the following steps of obtaining 2-cyano-3-(1,3-dioxolan)ethyl propionate after 2-bromomethyl-1,3-dioxolane and ethyl cyanoacetate which are used as the raw materials react with alkaline matter as the catalyst; conducting cyclization on obtained 2-cyano-3-(1,3-dioxolan)ethyl propionate and formamidine acetate with alkaline matter as the catalyst, and adding hydrochloric acid for hydrolysis cyclization to obtain pyrrolo[2,3-d]pyrimidin-4-ol; making obtained pyrrolo[2,3-d]pyrimidin-4-ol react with phosphorus oxychloride to obtain 4-chloropyrrolo[2,3-d]pyrimidine.The method for preparing 4-chloropyrrolo[2,3-d]pyrimidine is simple in technological process, the requirement for production conditions is low, the product is easy to purify and high in yield, and the production efficiency and product quality of 4-chloropyrrolo[2,3-d]pyrimidine are remarkably improved.

The invention relates to a method for preparing solid base catalyst with high specific surface by hybrid composite precursors, belonging to the technical field of preparation of composite metal oxide. The method comprises the following steps of: according to the characteristics of designability in structure and adjustability in laminate composition of laminated composite metal hydroxide, introducing a certain amount of Mg and Al, or Ca, Cu, Co, In and Ga on the laminate, preparing laminated compound, obtaining hybrid composite precursors by hybridization with carbon, then conducting high-temperature roasting on the precursors and obtaining the solid base catalyst of composite metal oxide with high specific surface and mesoporous structure. Due to introduction of the carbon into the precursors, the composite metal oxide obtained by the method has the characteristics of narrow pore size distribution and large specific surface area and the like, and the application of the catalyst in Knoevenagel condensation reaction of benzaldehyde and ethyl cyanoacetate shows good base catalytic activity.

The present invention relates to a process for synthesizing ethyl-2,3-dicyano-propionate which is used for produce pesticide intermediate. The basic method of said process includes the following steps: using the raw materials of ethyl cyanoacetate, paraformaldehyde and sodium cyanide to synthesize ethyl-2,3-dicyano-propionate in the medium dimethyl sulfoxide; after the ethyl-2,3-dicyano-propionate is synthesized, using solvent dichloromethane to extract the synthesized ethyl-2,3-dicyano-propionate from medium dimethyl sulfoxide, reduced pressure desolventizing to obtain crude product, then rectifying said crude product so as to obtain the refined product ethyl-2,3-cyano-propionate. Said invention also provides the concrete requirements of the above-mentioned every step. The purity of the obtained product is greater than 98%.

The invention provides a novel method for synthesizing 4-chloropyrrolo[2,3-d]pyrimidine, belonging to the technical field of chemical synthesis. The method comprises the steps of carrying out four-step reaction by using ethyl cyanoacetate, thiourea, caustic alcohol, 2-chloroacetaldehyde and sodium acetate as raw materials and using alcohol, ammonia water, water and phosphorus oxychloride as solvents as well as using active nickel as a catalyst to obtain the 4-chloropyrrolo[2,3-d]pyrimidine as a target product; and carrying out data representation by liquid chromatogram, nuclear magnetism spectrogram and mass spectrum. The invention has short process route and production cycle, low synthesis cost, safe and reliable synthesis and simple and convenient posttreatment method, and avoids the use of dangerous goods of sodium hydride. The product prepared by the method has high yield (50-58 percent) and high purity (98-99 percent).

The invention discloses a preparation method of a Cangrelor intermediate. The preparation method comprises the following steps of enabling ethyl cyanoacetate and thiourea to perform closed-loop reaction to generate a product under the alkaline condition, reacting the product and trifluoropropane under the alkaline condition, performing nitration reaction and reduction reaction, and performing closed-loop reaction with formic acid; chlorinating the generated product, and performing condensation reaction on the product and 2-(thiomethyl)ethylamine under the alkaline condition; reacting the obtained product and 1,2,3,5-tetraacetyl-beta-D-ribofuranose under the actions of alkylating agent and TMSOTF (trimethylsilyl trifluoromethanesulfonate), and hydrolyzing the product under the alkaline condition, so as to obtain the Cangrelor intermediate. The preparation method has the advantages that the silica-gel column chromatography is not needed, so that the technology cost is greatly reduced; the carbon disulfide, fuming nitric acid or concentrated sulfuric acid is not used in the preparation process, so that any danger is avoided; the noble metal hydrogenating reducing agent is not needed, so that the cost is reduced, and the operation danger is decreased; the operation is easy, safe and reliable, and the preparation method is suitable for large-scale industrial production.

The invention relates to a malononitrile synthesis method and belongs to the technical field of malononitrile synthesis. The malononitrile synthesis method comprises the following steps of 1, adding methanol or ethanol into a reactor, feeding ammonia gas into the reactor at a temperature of -20 to 50 DEG C, dropwisely adding methyl cyanoacetate or ethyl cyanoacetate into the reactor at a temperature of -20 to 50 DEG C, after dropwise addition, carrying out heat-preservation stirring, carrying out reduced pressure degasification until a temperature is reduced to below -10 DEG C and carrying out filtration and drying to obtain cyanoacetamide, and 2, mixing a dehydrant, a catalyst, cyanoacetamide and a solvent, heating the mixture for a reflux reaction lasting for 6h, carrying out cooling and filtration, removing the solvent to obtain a crude product, and carrying out reduced pressure rectification to obtain a malononitrile product. The preparation method has less reaction processes, can be operated simply, has a high yield and good product purity, utilizes cheap and easily available raw materials, greatly reduces a production cost, is free of an adsorbent, has a less phosphorous oxychloride use amount, greatly reduces three wastes, realizes easy recovery and recycle of the solvent, is suitable for industrial production and solves the problems of the existing a malononitrile synthesis method.

The invention belongs to the field of adhesives, and particularly relates to a synthesis technique of an alpha-cyanoacrylate monomer, which comprises the following steps: (1) directly reacting cyanoacetate and polyformaldehyde, which are used as raw materials, under solventless conditions by using a basic catalyst; (2) naturally cooling, keeping the temperature, and dehydrating to obtain the crude product; and (3) in the presence of a polymerization inhibitor, preparing the alpha-cyanoacrylate monomer, wherein the basic catalyst in the step (1) is one or mixture of hexahydropyridine, pyridine and KOH, the cyanoacetate is one or mixture of methyl cyanoacetate, ethyl cyanoacetate and n-butyl cyanoacetate, the polymerization inhibitor in the step (3) is hydroquinone and sulfur dioxide, a dehydrating agent is used for dehydration in the step (2); and the dehydrating agent is one or mixture of benzene, methylbenzene and methanol. The reaction process has the advantages of no need of organic solvent, low energy consumption, obvious environmental protection effect and high target product yield.

The invention belongs to the technical field of medicines and in particular relates to 2-amino-6-chloropurine as well as a synthesis method, an intermediate and application thereof. The synthesis method of the 2-amino-6-chloropurine comprises the following steps: performing a primary reaction, namely mixing ethyl cyanoacetate, chloroformamidine hydrochloride, liquid ammonia and sodium to implementa reaction so as to generate an intermediate; performing a secondary reaction, namely mixing the intermediate with formic acid to implement a reaction; adding a sodium hydroxide solution into the product of the secondary reaction till alkali; and performing filtering and drying, so as to obtain 2-amino-6-chloropurine. Raw materials are low in price and easy to obtain, reaction steps are small, the reaction time is short, a large amount of wastewater is not generated, and industrial production can be facilitated.

The invention discloses a method for synthesizing cyanoacetylene derivatives. The prior preparation method has high production cost and low yield, and is not suitable for industrial production. The method comprises that: in the presence of a dehydrating agent, organic formic acid generates organic formyl chloride; in the presence of Lewis acid and organic alkali, the organic formyl chloride is reacted with ethyl cyanoacetate to generate alpha-cyano-beta-carbonyl ethyl propionate compounds; in the presence of chlorinating agent and organic alkali, the alpha-cyano-beta-carbonyl ethyl propionatecompounds are subjected to chlorination reaction to generate alpha-cyano-beta-chloroacrylate ethyl ester compounds; in the presence of inorganic alkali and lower alcohol solution, the alpha-cyano-beta-chloroacrylate ethyl ester compounds are hydrolyzed to generate alpha-cyano-beta-chloroacrylate compounds; and in the presence of organic alkali, the alpha-cyano-beta-chloroacrylate compounds are subjected to decarboxylation and dehalogenation elimination reaction to generate the cyanoacetylene derivatives. The whole process operation is simple and convenient, the post treatment is simple and the yield is high, so the method is quite suitable for industrialized production.

The invention discloses a thiouracil derivative. The chemical formula is shown in the formula I, wherein R1 is hydrogen, halogen or aromatic group, R2 is hydrogen, halogen or alkyl group from C1 to C6. Simultaneously, the invention also discloses a method for synthesizing the derivative. The method comprises the following steps : adopting aromatic aldehyde or an aromatic amine compound as a starting material, and reacting the aromatic aldehyde, ethyl cyanoacetate and thiourea under the catalysis of piperidine to obtain a compound II; reacting chloromethyl-benzoyl chloride and potassium thiocyanate in a methylbenzene/water/TBAB system to obtain a compound III; reacting the compound III and aromatic amine in an acetonitrile solvent to obtain a compound IV, reacting the compound II and the compound IV with the equal mole in the acetonitrile solvent under the catalytic action of potassium carbonate to obtain a target product, i.e., a compound I. The method adopted is simple, the operation is easy, and the large-scale production is easy; and verified by experiment, the prepared compound I has stronger bacteriostatic activity and can be widely applied in bacteriostatic medicine preparations.

The invention relates to a dihydrooxazolo[5,4-d]pyrrolo[1,2-a]pyrimidine-9(5H)-one derivative and application. The preparation method comprises the following steps: by taking ethyl cyanoacetate as an initial raw material, generating a hydroxylamine compound (A) under the action of sodium nitrite and phosphoric acid, reducing with sodium hydrosulfite to obtain ethyl 2-aminocyanoacetate (B), reacting with different substituted acyl chlorides respectively under an alkali condition, generating different substituted oxazole compounds D1-D48 of 5-amino-4-formate under the action of trifluoroacetic acid, and reacting with pyrrolidone under the action of phosphorus oxychloride to obtain a dihydrooxazolo[5,4-d]pyrrolo[1,2-a]pyrimidine-9(5H)-one compound E1-E48. According to the invention, the inhibition activity of 48g of the compounds on Hela cervical cancer cells, MCF7 breast cancer cells and A549 lung cancer cells is investigated, and results show that the compounds E5, E10, E13, E16, E18, E19, E24, E42 and E43 have inhibition activity on Hela cervical cancer cells, the compounds E22, E24, E47 and E48 have inhibitory activity on MCF7 breast cancer cells, and the compounds E18 and E20 have inhibitory activity on A549 lung cancer cells.

The invention relates to a fluopyram preparation method, which sequentially comprises: (1) carrying out a substitution reaction on 2,3-dichloro-5-trifluoromethylpyridine and ethyl cyanoacetate or methyl cyanoacetate at a temperature of 30-160 DEG C in the presence of an alkali and a solvent, adjusting the reaction liquid to an acidic pH value after completing the reaction, and carrying out a decarboxylation reaction at a temperature of 80-160 DEG C to obtain 3-chloro-5-(trifluoromethyl)-2-acetonitrilepyridine; and (2) carrying out tandem hydrogenation and condensation reaction on the 3-chloro-5-(trifluoromethyl)-2-acetonitrilepyridine prepared in the step (1) and o-trifluoromethylbenzoyl chloride at a temperature of 20-100 DEG C in the presence of a catalyst, hydrogen, an alkali and a solvent to obtain fluopyram. According to the present invention, the preparation method has the short steps, avoids the unnecessary protection-deprotection step, is economical and environmentally friendly, and is suitable for industrial production.

The invention discloses thiouracil derivatives containing oxadiazole/thiadiazole, and further provides a method for synthesizing the thiouracil derivatives. The general chemical formula of the thiouracil derivatives is shown in figure I or figure II, wherein R1, R2 and R3 are hydrogen or halogen or aryl-. The method includes the steps of making aromatic aldehyde react with ethyl cyanoacetate and thiourea under the catalysis of piperidine to obtain a compound III, making aromatic aldehyde react with semicarbazide to obtain a compound IV, making the compound IV react with bromine to obtain a compound V, making the compound V react with benzoyl chloride to obtain a compound VI, making the compound VI and the compound III have a reflux reaction under the catalysis of potassium carbonate to obtain the general chemical formula I, making aromatic acid react with thiosemicarbazide to obtain a compound VII, making the compound VII react with benzoyl chloride to obtain a compound VIII, and making the compound VIII react with the compound III under the catalysis of potassium carbonate to obtain the general chemical formula II. The adopted method is simple, easy to operate and beneficial to large-scale production; it is verified that the prepared compound has high bacteriostatic activity and can be widely applied in bacteriostatic drug preparations.

The invention relates to a method for synthesizing an important intermediate 2-chloro-3-amino-4-methylpyridine for an anti-AIDS medicament Nevirapine, and belongs to the technical field of organic synthesis. The method comprises the following process steps that: ethyl cyanoacetate and acetone are dehydrated and condensed to generate a condensation compound I under the action of a catalyst; dimethyl formamide, dimethyl sulfate and sodium methoxide solution react to generate N,N-dimethylformamiade dimethyl acetal (N,N-dimethyl formamide A), and then the N,N-dimethylformamiade dimethyl acetal reacts with the condensation compound I to generate conjugated enamine, namely a condensation compound II; the condensation compound II is cyclized by hydrochloric acid and ethanol to form a cyclic compound 2-chloro-4-methyl-ethyl nicotinate; the 2-chloro-4-methyl-ethyl nicotinate is ammonolyzed by ammonia gas to form 2-chloro-4-methyl-niacinamide; and the 2-chloro-4-methyl-niacinamide is subjected to Hofmann degradation reaction to form the 2-chloro-3-amino-4-methylpyridine. Compared with the prior synthesizing method, the method of the invention has the remarkable characteristic of reducing the reaction steps, and is suitable for large-scale industrialized production; the molar total yield of the five-step reaction is improved to 27 percent from the prior 24 percent; and the purity of the product reaches over 99 percent.

The invention discloses a production method of carnosine, which is characterized by comprising the following steps of: synthesizing N-acetyl cyanide-L-histidine through ammonolysis reaction by using L-histidine and ethyl cyanoacetate as raw materials and sodium alcoholate as a catalyst; and then obtaining L-carnosine through the intermediate by using stronger ammonia water and alcohol as a solvent in a high-pressure reaction kettle and using a Pd-Rh/C composite catalyst for catalytic hydrogenation under the protection of nitrogen, wherein the overall yield of two-step reaction achieves 72 percent. The invention has simple process, easy operation, low cost, and the like and is very suitable for industrialized production.

The invention discloses a method for synthesizing pregabalin with isobutyl butanedinitrile as the intermediate. The method includes the steps of conducting the Knoevenagel condensation reaction on isovaleraldehyde and ethyl cyanoacetate in cyclohexane solvent with piperazine as the catalyst, conducting Michael addition on the product obtained in the first step and cyanic acid in alkaline alcohol solvent, conducting the decarboxylic reaction on the product obtained in the second step in isopropanol solvent under the heating condition to obtain the isobutyl butanedinitrile solvent, conducting hydrolysis on the intermediate under catalysis of cyanide hydratase AtNiTl, and conducting catalytic hydrogenation with raney nickel as the catalyst. According to the method, isoamyl aldehyde and ethyl cyanoacetate which are low in price and easy to obtain are used as raw materials, and the isobutyl butanedinitrile intermediate is obtained through the Knoevenagel condensation reaction, Michael addition and the decarboxylic reaction. The intermediate is then catalyzed, hydrolyzed and reduced through cyanide hydratase AtNiTl, and pregabalin is obtained. The reaction route is simple, the yield of each step of reaction is high, and therefore the final total recovery and purity of pregabalin are ensured.

The invention provides a production process for an alpha-cyanoethyl acrylate adhesive. The production process comprises the following steps: under the action of a catalyst, subjecting ethyl cyanoacetate, solid formaldehyde and an organic solvent to condensation polymerization in a reaction vessel so as to obtain a reaction system; then adding an organic solvent into the reaction system from the bottom of the reaction vessel and then carrying out condensation, reflux and dehydration; and finally, adding an auxiliary agent into the reaction system obtained in the previous step and carrying out a cracking reaction so as to obtain the alpha-cyanoethyl acrylate adhesive. The production process employs specific reaction steps, so yield is further improved, and production cost is reduced; and in particular, after completion of condensation polymerization and synthesis reaction of materials, the organic solvent is added from the bottom of reaction vessel and an external reflux and dehydration manner is employed, so dehydration is more thorough, removal of a trace amount of moisture is much easier, stability of the adhesive is improved, and the shelf-life of the adhesive is further prolonged.

The invention discloses a synthesis method of fluopyram and belongs to the technical field of fine chemical engineering. The synthesis method comprises the following steps: by taking 2,3-dichloro-5-trifluoromethylpyridine as a raw material, performing condensation and hydrolysis decarboxylation with ethyl cyanoacetate in the presence of an alkali so as to obtain 2-acetonitrile-3-chloro-5-trifluoromethylpyridine; performing catalytic hydrogenation reduction so as to obtain 2-ethylamino-3-chloro-5-trifluoromethylpyridine, performing protection by using o-trifluoromethyl benzoic anhydride or o-trifluoromethyl benzoic acid-trimethylacetic anhydride, so as to obtain a target product, namely fluopyram. The synthesis method is reasonable and simple and convenient in route selection and is applicable to industrial amplification, the synthesis method breaks through a conventional process, a step that hydrogenation reduction is implemented and at the same time amino is protected by using other acylation reagents firstly, and acylation of the amino with o-trifluoromethyl benzoyl chloride is implemented later is avoided, a step that hydrogenation is implemented and at the same time protectionis implemented to obtain the target product amide is implemented instead, and process procedures can be simplified.

The invention discloses a bifunctional fluorescent probe for detecting HSO3- and hydrazine hydrates and a preparation method and application of the probe. The preparation method comprises the steps ofcarrying out a condensation reaction on 3-(4'-formyl-1',1'-biphenyl-4'-carbonyl) norpinone and 2-ethyl cyanoacetate to obtain 3-(4'-((2-cyano) ethyl acrylate)-1',1'-biphenyl-4'-carbonyl) norpinone; making 3-[4'-(1-cyano-2-ethoxycarbonyl)vinyl-1',1'-biphenyl-4'-carbonyl] norpinone react with boron trifluoride diethyl ether to obtain a 3-[4'-(1-cyano-2-ethoxycarbonyl)vinyl-1',1'-biphenyl-4'-carbonyl] norpinone-based fluorine-boron complex. After the 3-(4'-((2-cyano) ethyl acrylate)-1',1'-biphenyl-4'-carbonyl) nopinone fluorine-boron complex prepared by means of the method is complexed with HSO3- ions, the fluorescence color of a solution is changed from blue green to blue. After a reaction with the hydrazine hydrates, the fluorescence color of the solution is changed from blue green to yellow, and the probe can be used as a bifunctional fluorescence probe and has a good application prospect in the aspect of identifying the HSO3- ions and the hydrazine hydrates.