139 results about "Metaclazepam" patented technology

The invention discloses a 5-bromoindole-2-carboxylic acid methyl ester derivative as well as a preparation method and application thereof in a protein inhibitor, and relates to the technical field of synthesis and preparation of inhibitors. According to the 5-bromoindole-2-carboxylic acid methyl ester derivative, compared with a contrast product, the synthetic route steps of the prepared 5-bromoindole-2-carboxylic acid methyl ester derivative are simpler and more convenient, structural modification and preparation are easier, the application range of a substrate is widened, the yield of the product is increased, and the yield of the product is increased. The differentiated requirements on the molecular structure novelty in the field of kinase inhibitors can be met. An epidermal growth factor receptor (EGFR) inhibitor prepared from the 5-bromoindole-2-carboxylic acid methyl ester derivative is higher in inhibition efficiency on biological activity, the physiological solubility is improved more remarkably, a more excellent and stable target binding result can be shown, and the EGFR inhibitor can be used for preparing an epidermal growth factor receptor (EGFR) inhibitor. The application effect of the compound in scenes such as antitumor drug development and the like is favorably improved.

The present application relates to a kind of chalcone amide alpha-glucosidase inhibitors and its preparation and application, the inhibitor structural formula is: preparation method specifically is (1) after 2-hydroxyacetophenone, sodium hydroxide and methyl p-formylbenzoate are reacted, intermediate in formula (a) is obtained after post-processing;(2) intermediate in formula (a) is dissolved in organic solvent and potassium hydroxide is reacted, after reaction, intermediate in formula (b) is obtained after post-processing;(3) intermediate in formula (b) and substituted aniline are dissolved in organic solvent, after reaction, the inhibitor shown in formula (c) is obtained after post-processing.Compared with prior art, the compound of the present application is novel, and experiments show that it has good alpha-glucosidase inhibitory activity, and can be used for preparing alpha-glucosidase activity inhibiting drug.

The invention discloses a phenoxazine skeleton-containing drug small molecule and application thereof, and belongs to the technical field of synthesis of heterocyclic compounds and antitumor drugs, the phenoxazine skeleton-containing drug small molecule has an inhibition effect on HepG2 and A549, a phenoxazine derivative 7c with the third site connected with a methoxy group at the tail end of a phenoxazine structure benzene ring has a better overall effect, and the phenoxazine skeleton-containing drug small molecule can be applied to preparation of antitumor drugs. The inhibition rates of the compound on HepG2 and A549 are respectively 87.67% and 94.23%. 7g of the phenoxazine derivative of which the methyl ester structure is connected to the third site of the phenoxazine structure only has an obvious effect on A549, and the inhibition rate in A549 cells is 96.00%.

The invention discloses a preparation method and application of a compound with a cold sensing regulation effect, which comprises the following steps: dissolving tryptophan in methanol, adding concentrated sulfuric acid, esterifying the acid to protect carboxyl so as to obtain tryptophan methyl ester, dissolving the obtained tryptophan methyl ester and aromatic carboxylic acid substances in N, N-dimethylformamide, and reacting to obtain the compound with the cold sensing regulation effect. The method comprises the following steps: catalyzing 2-(7-azabenzotriazole)-N, N, N ', N'-tetramethylurea hexafluorophosphate and N, N-diisopropylethylamine, dissolving a catalyzed product in ethanol (98%), adding into a NaOH solution, stirring, carrying out rotary evaporation treatment, slowly dropwise adding a 0.5 mol / L hydrochloric acid solution, adjusting the pH value of a reaction system to 3-4, and finally obtaining the tryptophan derivative compound with the yield of 70%. The invention provides a potential medicine for improving the working ability and cold injury in the cold environment for people living and working in the cold environment, and is developed into a medicine for effectively improving neuropathic pain diseases in the cold environment.

The invention discloses a synthesis method of a Vinetoram key intermediate and Vinetoram, and relates to the technical field of organic synthesis.The synthesis method comprises the steps that 1-((4 '-chloro-5, 5-dimethyl-3, 4, 5, 6-tetrahydro-[1, 1'-biphenyl]-2-yl) methyl) piperazine hydrochloride and 2-((1H-pyrrolo [2, 3-b] pyridine-5-yl) oxy)-4-bromobenzoic acid methyl ester are used as reaction raw materials, a reaction is carried out, and the Vinetoram key intermediate and the synthesis method of the Vinetoram key intermediate are synthesized; the method comprises the following steps: carrying out a substitution reaction and a hydrolysis reaction to obtain a key intermediate of the Venotocork, and carrying out a condensation reaction on the intermediate and 3-nitro-4-((tetrahydro-2H-pyran-4-yl) methylamino) benzenesulfonamide to obtain the Venotocork. The synthesis method has the advantages of short process route, easily available raw materials, mild reaction conditions, high yield and purity of the intermediate and the Vinetoram, facilitation of the improvement of the yield and quality of the Vinetoram, and reduction of the production cost of the Vinetoram.

The utility model discloses a production system of 1-cyclopropyl-3-(2-methylthio-4-trifluoromethylphenyl) propyl-1, 3-diketone, which comprises an esterification unit and a condensation unit, and is characterized in that the esterification unit is connected with the condensation unit; the production system has the advantages that the production system is simple in connection structure and easy to implement, methyl 2-methylthio-4-trifluoromethyl benzoate is prepared from 2-methylthio-4-trifluoromethyl benzoic acid and the like through an esterification unit and then reacts with cyclopropyl ketone and other raw materials to prepare 1-cyclopropyl-3-(2-(methylthio)-4-(trifluoromethyl) phenyl) propyl-1, 3-diketone, and the production system has the advantages that the production system is simple in connection structure and easy to implement. The generation of three wastes is reduced, and the production cost is reduced; moreover, in the reaction process, the reaction temperature is not high, the reaction condition is mild, the yield is high, the production cost is low, the content of impurities in the product 1-cyclopropyl-3-(2-(methylthio)-4-(trifluoromethyl) phenyl) propyl-1, 3-diketone can be reduced, a high-quality reaction raw material is provided for subsequent industrial production of isoxaflutole, and the method is suitable for large-scale industrial production.

The invention belongs to the technical field of medicines, and particularly relates to a beta-elemene tryptophan methyl ester derivative and application thereof in preparation of antitumor drugs. According to the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I), on the basis of maintaining a beta-elemene structural framework, a tryptophan methyl ester group is introduced to the 13th site of beta-elemene, and unsubstituted C3-7 heterocycloalkyl, substituted C3-7 heterocycloalkyl, unsubstituted C5-11 hetero-spirocycloalkyl or substituted C5-11 hetero-spirocycloalkyl is introduced to the 14th site of beta-elemene, so that the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I) is obtained. The water solubility and the pharmacokinetic property of the compound are effectively improved. Experimental results show that the anti-tumor activity of the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I) provided by the invention is obviously enhanced compared with that of beta-elemene. Formula (I).

The invention belongs to the field of Velciguat synthesis, and particularly relates to a preparation method of Velciguat and an intermediate product thereof. The preparation method of the Velciguat comprises the following steps: (1) reacting aminomalononitrile with methyl chloroformate to generate an intermediate product I; (2) carrying out ring closing on the intermediate product I and formamidine under an alkaline condition to obtain an intermediate product II; (3) carrying out bromination reaction on the intermediate product II and N-bromosuccinimide to obtain an intermediate product III; (4) reacting the intermediate product III with bis (pinacolato) diboron under the action of a catalyst to obtain an intermediate product IV; and (5) carrying out a reaction on the intermediate product IV and 5-fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo [3, 4-b] pyridine to prepare the viriciguat. The method is simple to operate, low in cost and safe in production. The invention also provides the intermediate product obtained by the preparation method.

The application relates to a preparation method of a benzylamine compound and belongs to the field of organic synthesis. The preparation method of the benzylamine compound is as follows: a reaction formula is shown in the description. The application also provides a preparation method of the compound of the above formula (VI). Compared with methyl o-bromomethylbenzoate used in the prior art, methyl o-chloromethylbenzoate used in the application is cheaper, has lower preparation cost, less pollution and is more environment-friendly. Compared with the prior art, the benzylization reaction of the application has higher reaction conversion rate, less dibenzyl impurities, is convenient for product post-treatment and purification, has higher yield, and has better product quality.

Fungicidal compositions comprising carboxamides The present invention relates to fungicidal compositions comprising at least one compound selected from the group consisting (I-1) N-[1,3-dimethyl-1-(phenylmethyl)butyl]-8-fluoro-3- quinolinecarboxamide, (I-2) N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3- carboxamide, (I-3) N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide, as active component 2) at least one compound, or an N-oxide, or an agriculturally useful salt thereof, selected from the group consisting of (II-1) methyl 2-[2-chloro-4-(4- chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate, (II-2) fluoxytioconazole, (II-3) flumetylsulfurim, (II-4) pyrapropoyne, wherein the weight ratio of compound I to compound II is from 10:1 to 1:10. The invention also relates to an agrochemical composition comprising the composition and a solvent of solid carrier. Further, the invention relates to a non-therapeutic use of the inventive compositions controlling phytopathogenic harmful fungi.

The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of a benzofuran compound. In an inert gas environment, a 2-fluorotoluene compound as shown in a formula 1 and a methyl benzoate compound as shown in a formula 2 are mixed and reacted with an organic solvent methyl tert-butyl ether in the presence of bis (trimethylsilyl) amino cesium and cesium sulfate, and the benzofuran compound as shown in a formula 3 is synthesized under a heating condition. Wherein the methyl benzoate compound as shown in the formula 2 can also be replaced by 2-naphthoic acid methyl ester or 1-naphthoic acid methyl ester. The research develops a benzofuran synthesis strategy without transition metal catalysis. According to the method, on the basis of commercially available raw materials, the construction of a benzofuran skeleton is realized through a simple and efficient path. Due to the mild and green reaction characteristic, a route with practical value is provided for synthesis of active medicine molecules and key intermediates of the active medicine molecules.

An agent containing at least one aroma compound selected from the group consisting of E-beta-damascone, S-(2-methyl-3-furyl)ethanethioate, beta-caryophyllene oxide, beta-ionone, 2,5-dihydroxy-1,4-dithiane, methyl anthranilate, S-furfuryl thioformate, 1-isothiocyanate-3-(methylthio)propane, nootkatone, 1,4-dioxacycloheptadecane-5,17-dione, sclareol, and sclareolide is effective for masking an unpleasant smell and for making oral products in which an unpleasant smell is masked.

This invention provides an birepiperazole oral solution, wherein the solution comprises birepiperazole 0.4-0.6 mg / ml, disodium edetate 0.1-0.5 mg / ml, methylparaben 1.5-2.0 mg / ml, propylparaben 0.15-0.25 mg / ml, an acidic pH adjuster 2.5-3.5 mg / ml, a flavoring agent 0.8-1.2 mg / ml, propylene glycol 40-60 mg / ml, glycerin 120-180 mg / ml, and a sodium hydroxide solution to adjust the pH to 2.9-3.3. The drug exhibits high stability during preparation, storage, and clinical formulation.

Methods for preparing an L-6-hydroxytryptophan (HTP) derivative and intermediates thereof are provided. The methods for preparing the various intermediates of the L-6-HTP derivative are provided, on the basis of which the L-6-HTP derivative could be obtained. Specifically, the L-6-HTP derivative is obtained by using a compound A6-0 with a structure shown in Formula 1 as a starting reaction raw material, and subjecting the compound A6-0 to triisopropylsilyl (TIPS) protection, coupling, carbon-boron bond oxidation, hydroxyl-targeted benzyl protection, TIPS protective group removal, tert-butoxycarbonyl (Boc) protective group removal, methyl ester hydrolysis, and amino-targeted 9-fluorenylmethoxycarbonyl (Fmoc) protection in sequence.

Described herein are processes for the synthesis of P2X3 antagonists, wherein the P2X3 antagonist is methyl (S)-2-((2-(2,6-difluoro-4-(methylcarbamoyl)phenyl)-7-methylimidazo[1,2-a]pyridin-3-yl)methyl)morpholine-4-carboxylate (Compound 1), or a pharmaceutically acceptable salt or co-crystal thereof.

The invention provides application of mycophenolic acid methyl ester in preparation of antithrombotic drugs, and belongs to the technical field of antithrombotic drugs. The antithrombotic activity of the compound mycophenolic acid methyl ester is found for the first time, and experimental support and theoretical basis are provided for developing novel drugs for treating or preventing thrombus.

The application discloses a stable isoniazid oral solution, which comprises isoniazid, hydroxybenzyl methyl ester, hydroxybenzyl propyl ester, a pH regulator and a solvent. The application prepares the isoniazid oral solution with good stability, improves the absorption and utilization rate of the medicament, and has good taste and market prospect.

Described herein are two processes for the preparation of methyl (5)-2-((2-(2,6-difLuoro-4-(methylcarbamol)phenyl)-7-methylimidaz[1,2-a]pyridine-3-yl)methyl)morpholine-4-carboxylate, a P2X3 antagonist, in a stepwise manner and chemical intermediates used in the synthetic processes.

The present invention relates to a method for efficiently producing a compound derived from the commercially available and readily available 3-((3S)-7-bromo-2-((2-hydroxypropyl)amino)-5-(pyridin-2-yl)-3H-benzo[e][1,4]diazepine-3-yl)propionate methyl ester, namely, the compound 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepine-4-yl]propionate methyl ester benzenesulfonate (remimazolam besylate).

The invention discloses a continuous synthesis method of 1-(2-chlorphenyl)-2-(2-tetrazolyl) ethanone, which comprises the following steps: (1) introducing a trimethylsilylated diazomethane solution and a strong alkali solution into a micro-channel reactor 1 for reaction, introducing the obtained intermediate reaction solution and a 2-chloromethyl benzoate solution into a micro-channel reactor 2 for continuous reaction, the preparation method comprises the following steps: adding 2-chlorophenyl to generate 1-(2-chlorophenyl)-2-(2-tetrazolyl-trimethylsilane) ethanone; and (2) removing a TMS group from the 1-(2-chlorphenyl)-2-(2-tetrazolyl-trimethylsilane) ethanone, and then carrying out post-treatment to obtain the 1-(2-chlorphenyl)-2-(2-tetrazolyl) ethanone. The continuous synthesis method uses a fluid process, has the advantages of small amplification effect, high production efficiency and environmental protection, improves the selectivity of 2-tetrazole, and avoids partial sensitization of intermediates.

The application belongs to the field of chemical industry, and particularly relates to a synthesis method of a substituted pyrazoloquinazoline derivative. The method provided by the application comprises sequentially preparing 2-chloro-5,6,7,8-tetrahydroquinazoline, 2-chloro-6,7-dihydroquinazolin-8(5H)-ketoxime, 2-chloro-6,7-dihydroquinazolin-8(5H)-ketone, 2-(2-methoxy-8-oxo-5,6,7,8-tetrahydroquinazolin-7-yl)-2-oxoacetic acid methyl ester and 1-(2-hydroxyethyl)-8-methoxy-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid methyl ester, and finally obtaining 1-(2-hydroxyethyl)-8-((5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl)amino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide. By using the method of the application, three reaction steps are reduced, the total yield is increased by nearly one time, and the method is far higher than the original process route; and the application of dangerous reagents such as hydrazine hydrate and iodine is avoided, and the method is easy to scale up.

The invention discloses a formaldehyde probe as well as a preparation method and application thereof, and belongs to the technical field of fluorescent probe preparation. Dissolving benzylamine and potassium carbonate in anhydrous acetonitrile, adding 2-bromo-2-methyl propionate, and reacting to obtain a compound 3; dissolving the compound 3 and lithium hydroxide in a mixed solution of tetrahydrofuran and water, reacting for a period of time, and quenching the reaction with hydrochloric acid to obtain a carboxylic acid intermediate 4; and dissolving the carboxylic acid intermediate 4 in dichloromethane, then adding CDM, EDCI and DMAP, and carrying out a reaction to obtain the target product DPM. The DPM is a formaldehyde regeneration type fluorescent probe and can realize formaldehyde detection in a mode of disturbing an endogenous steady state to the minimum extent. The DPM is a steady-state maintenance type formaldehyde probe successfully applied to a spinal cord injury (SCI) model for the first time, and can realize visual monitoring on formaldehyde rise of a diseased region based on a non-invasive living imaging system (IVIS).

The invention relates to a preparation method of a photo-crosslinking agent compound (N-(19-(3-(butyl-3-alkyn-1-yl)-3H-diazacyclopropane-3-yl)-4, 16-dioxo-7, 10, 13-trioxo-3, 17-diazacylalkyl)-4-(7-oxo-7H-furan [3, 2-g] benzopyran-9-yl) oxy) butyramide), which comprises the following steps: by taking xanthoxyl as a starting material, reacting at the temperature of 60-80 DEG C for 1-2 hours, and then adding a catalyst, thereby obtaining the photo-crosslinking agent compound. The method comprises the following steps: sequentially carrying out condensation with fragments such as methyl 4-chlorobutyrate, BOC-ethylenediamine, polyoxydipropionic acid and diaziridine, so as to obtain a high-purity compound with a photo-crosslinking probe effect. The preparation method provided by the invention has the advantages of mild and controllable reaction conditions, high yield and no column chromatography purification operation in post-treatment purification, and is suitable for industrial large-scale production.

The invention discloses a method for synthesizing loxapine succinate, which comprises the following steps of: carrying out substitution reaction by using 2-nitrofluorobenzene and 2-hydroxy-4-chloromethyl benzoate as raw materials to generate 5-chloro-2-(2-nitrophenoxy) benzoate; nitryl is reduced, and 5-chloro-2-(2-aminophenoxy) benzoate is generated; the method comprises the following steps: carrying out an intramolecular ring closing reaction to generate 2-chlorodibenzo [b, f] [1, 4] oxazepine-11 (10H)-ketone; 2, 11-dichlorodibenzo [b, f] [1, 4] oxazepine is obtained through a reaction and chlorination; the method comprises the following steps: carrying out a C-N coupling reaction of methyl piperazine to generate 2-chloro-11-(4-methylpiperidine-1-yl) dibenzo [b, f] [1, 4] oxazepine; and salifying with succinic acid to generate the loxapine succinate. The method is easily available in raw materials, simple in process and suitable for large-scale production.

The invention relates to a method for preparing fenbendazole by taking m-dichlorobenzene as a raw material. The method comprises the following steps: nitrating m-dichlorobenzene to obtain 1, 3-dichloro-4-nitrobenzene; the 4-chloro-3-nitrodiphenyl sulfide reacts with thiophenol salt to obtain 4-chloro-3-nitrodiphenyl sulfide; reacting with ammonia to obtain 4-amino-3-nitrodiphenyl sulfide; reducing to obtain 3, 4-diaminodiphenyl sulfide; and finally, cyclizing with methyl cyanate to obtain benthioimidazole. The method has the advantages that cheap m-dichlorobenzene is used as a starting raw material, benzenethiol is efficiently synthesized through nitration, thiophenol substitution, ammoniation, reduction and cyclization reaction, the defect that expensive or difficult-to-obtain raw materials are used in the prior art is avoided, and the method is novel in route, simple and convenient to operate, mild in reaction condition, high in total yield and suitable for industrial production.

The invention provides a preparation method of nirapalide tosylate, which is characterized in that 1H-indazole-7-carboxyl methyl ester, 2, 4-dimethoxybenzylamine and (S)-3-(4-bromophenyl) piperidine-1-carboxylic acid tert-butyl ester are used as raw materials to react to prepare the nirapalide tosylate. The method has the advantages of simple process operation, few side reaction products and high purity of the obtained product, and is suitable for industrial production of nirapalide tosylate.

The invention relates to the use of a compound of formula (I), wherein R1 is selected from the group consisting of a C1 to C6 hydrocarbon moiety, which is straight or branched, and contains saturated and / or unsaturated bonds, and up to one cyclic moiety; or is benzyl or phenethyl; and R2, R3, R4, R5, and R6 at the phenyl ring are independently selected from H and Me, wherein the compound according to formula (I) has one or two methyl groups at said phenyl ring, and wherein at least one of R2 or R3 is Me, as a fragrance; with the proviso that the compound of formula (I) is not methyl 2-methylbenzoate and ethyl 2- methylbenzoate.

The application belongs to the field of vixepiromide synthesis, and particularly relates to a preparation method of vixepiromide and intermediate products thereof. The preparation method of vixepiromide comprises the following steps: (1) reacting aminopropandinitrile with methyl chloroformate to generate an intermediate product one; (2) ring closing the intermediate product one with formamidine under alkaline conditions to generate an intermediate product two; (3) performing bromination on the intermediate product two with N-bromosuccinimide to generate an intermediate product three; (4) reacting the intermediate product three with pinacol diboron under the action of a catalyst to generate an intermediate product four; and (5) reacting the intermediate product four with 5-fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridine to generate vixepiromide. The application has the advantages of simple operation, low cost and safe production. The application further provides the intermediate products generated in the above preparation method.

This invention relates to a method for preparing methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, a raw material for synthesizing antioxidants 1010 and 1076. Specifically, this invention uses 2,6-di-tert-butylphenol and methyl 3-bromopropionate as reactants, adds an organic solvent, and reacts them in a reaction system under light and in the presence of a palladium catalyst to obtain methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate; furthermore, the reaction system also includes an alkaline additive. This invention provides a novel method for preparing methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate. By activating the C-H bond at the 4-position of the benzene ring of 2,6-di-tert-butylphenol, a methyl propionate group is directly attached to the 4-position of the benzene ring. Compared to existing technologies, this method does not require strong bases or highly toxic reagents and has a lower reaction temperature. This method has the potential to be an alternative to existing methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate preparation processes and a new route for obtaining synthetic raw materials for antioxidants 1010 and 1076.