230 results about "Metaclazepam" patented technology

The invention relates to the technical field of hydraulic fracturing exploitation of deep / ultra-deep oil and gas reservoirs, and discloses a gel-coated temporary plugging agent and a preparation method and application thereof.The gel-coated temporary plugging agent comprises a proppant inner core and a degradable gel shell coating the outer surface of the proppant inner core; the degradable gel shell is formed by a gel shell gelling solution, the gel shell gelling solution comprises small-molecule comonomers and a degradable cross-linking agent, and the small-molecule comonomers comprise acrylamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide the initiator is one or more of N, N-dimethylacrylamide, acrylic acid, hydroxyethyl acrylate, benzyl acrylate, 2-propyl acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid and N-vinyl pyrrolidone; and the initiator is one or more of N, N-dimethylacrylamide, acrylic acid, hydroxyethyl acrylate, benzyl acrylate, 2-propyl acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid and N-vinyl pyrrolidone. The gel-coated temporary plugging agent can be used for effectively plugging in a fracturing time period at high temperature / ultrahigh temperature, and the flow conductivity of fractured cracks can be enhanced by exposing an internal propping agent after the gel-coated temporary plugging agent is degraded.

The invention relates to a method for synthesizing trifloxystrobin through a one-pot method, and belongs to the technical field of organic synthesis.The method comprises the following steps that 1, E-2-(2-halomethylphenyl)-2-methoxyiminoacetic acid methyl ester, m-trifluoromethyl acetophenone, hydroxylamine hydrochloride or hydroxylamine sulfate and a solvent are added into a reaction flask, then alkali is added, and after addition is completed, a heat preservation reaction is conducted; and Step 2, after the reaction is finished, filtering to remove salt, and concentrating filtrate under reduced pressure to obtain trifloxystrobin. Compared with a traditional synthesis method of the trifloxystrobin, the synthesis method of the trifloxystrobin has the advantages that the 3-trifluoromethyl acetophenone and the E-2-(2-halomethylphenyl)-2-methoxyiminoacetic acid methyl ester are used as raw materials, the trifloxystrobin is directly synthesized by a one-pot method, the reaction route is short, the raw material cost is low, and the synthesis method of the trifloxystrobin by the one-pot method has the advantages that the synthesis efficiency is high, and the synthesis cost is low. The preparation method has the advantages that the preparation of m-trifluoromethyl acetophenone oxime from m-trifluoromethyl acetophenone is not needed, the whole synthesis process is simpler and more efficient, the reaction conditions are mild, and the preparation method is suitable for industrial large-scale production.

The invention discloses a preparation method of deuterated methylamine hydrochloride and a solid-phase continuous flow synthesis system, and relates to the technical field of deuterated synthesis. The preparation method comprises the following steps: adding out-of-phase polykadexide into methyl trifluoromethanesulfonate and 1, 2-dichloroethane for heating reaction, then adding methanol for quenching reaction, washing and drying to obtain an out-of-phase polykadexide type methyl reagent; the method comprises the following steps: adding a heterophase polysulfide-type methyl reagent into a mixed solvent of a polar solvent and heavy water, and carrying out alkali treatment to complete deuteration conversion, so as to obtain a heterophase polysulfide-type deuterated methyl reagent; the preparation method comprises the following steps: dissolving o-phenylsuccinimide in acetonitrile, and adding a heterophase polysulfide deuterium methyl reagent and inorganic alkali to react, so as to obtain N-(1, 1, 1-trideuterium methyl) benzo-succinimide; the preparation method comprises the following steps: hydrolyzing N-(1, 1, 1-trideuterium methyl) benzo-succinimide and hydrochloric acid in an aqueous solvent to obtain deuterated methylamine hydrochloride. The preparation method is simple, the deuterium source is cheap, the atom utilization rate is high, the deuteration rate is high, and the production cost is low.

The invention relates to the technical field of whitening and freckle removing, in particular to light-sensitive whitening and freckle removing essence and a preparation method and application thereof.The light-sensitive whitening and freckle removing essence is prepared from, by mass, 72.07% of water, 6% of butanediol, 3%-5% of X-resveratrol, 3% of tranexamic acid, 2.5% of nicotinamide, 2% of a red removing factor, 1% of panthenol, 1% of an anti-inflammatory agent, 0.5% of an anti-allergy agent, 0.5% of carnosine, 0.5% of p-hydroxyacetophenone, 1% of 1, 2-propylene glycol and the balance 1, 2-propylene glycol. The mask comprises the following components in percentage by weight: 0.5% of 1, 2-hexanediol, 0.2% of carbomer, 0.18% of arginine, 0.05% of sodium hyaluronate, 0.1%-1% of a light stabilizer and 5% of bis-ethylhexyloxyphenol sulfonate. According to the invention, the resveratrol is esterified by methyl propiolate, so that the molecular structure of the resveratrol is optimized, the performance of the resveratrol in the aspect of light stability is enhanced, and the degradation under the illumination condition is reduced; the esterified resveratrol can effectively inhibit tyrosinase activity, regulate melanocyte signal transduction and realize whitening and spot fading effects.

The invention belongs to the technical field of synthesis of ester compounds, and particularly relates to a preparation method of 2, 6-dichloro-4-cyanobenzoic acid methyl ester, which comprises the following steps: by taking dimethyl 2-aminoterephthalate as a raw material, sequentially carrying out substitution reaction, deamination reaction, hydrolysis reaction, amidation reaction and dehydration reaction to obtain the 2, 6-dichloro-4-cyanobenzoic acid methyl ester. The 2, 6-dichloro-4-cyanobenzoic acid methyl ester is prepared by the method, and the yield reaches 59.28%. The N-chlorosuccinimide is used as a chlorine source to carry out substitution reaction on the 2-amino dimethyl terephthalate, so that the potential safety hazard caused by the traditional chlorination reagent is avoided, and the tert-butyl nitrite used in the deamination reaction avoids the potential safety hazard caused by the use of strong corrosive sulfuric acid; the amidation reaction is completed in one step by adopting a condensing agent, so that the complicated operation caused by firstly preparing acyl chloride and then carrying out condensation reaction is avoided, and therefore, the preparation method has the characteristics of safe preparation process, environment friendliness, simplicity in operation and the like under the condition of ensuring the product yield and purity.

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 present invention relates to the field of pharmaceutical technology, and more particularly to a compound sodium picosulfate oral solution and a preparation method thereof. The oral solution comprises the following components: sodium picosulfate, anhydrous citric acid, magnesium oxide, a stabilizer, an antibacterial agent, and a pH adjuster, wherein the antibacterial agent comprises methylparaben and propylparaben in a mass ratio of 15:1-6:1. The present invention has the advantages of high stability and good antibacterial efficacy.

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.

Therapeutic compositions deliver a therapeutic amount of methylphenidate in a delayed and extended release formulation. The dosage form exhibits a lag time prior to release of from 6 to 8 hours or longer, followed by a sustained release period.

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 invention belongs to the technical field of compound preparation, and particularly provides a preparation method of L-glutamic acid-1-tert-butyl ester, which comprises the following steps: step S1, carrying out imidization reaction on an L-glutamic acid-5-methyl ester compound and benzophenone imine to generate N-dibenzylidene-L-glutamic acid-5-methyl ester; step S2, enabling the N-dibenzylidene-L-glutamic acid-5-methyl ester and tertiary butyl-2, 2, 2-trichloroacetic acid imine ester to be subjected to a tert-butyl esterification reaction, so as to generate N-dibenzylidene-L-glutamic acid-5-methyl ester-1-tert-butyl ester, and enabling the N-dibenzylidene-L-glutamic acid-5-methyl ester-1-tert-butyl ester to be subjected to a tert-butyl esterification reaction; and S3, carrying out hydrolysis reaction on the N-dibenzylidene-L-glutamic acid-5-methyl ester-1-tert-butyl ester to remove a methyl ester group, and removing a protecting group on an amino group, so as to generate the L-glutamic acid-1-tert-butyl ester. The preparation method disclosed by the embodiment of the invention is used for preparing the L-glutamic acid-5-methyl ester-1-tert-butyl ester from the N-dibenzylidene-L-glutamic acid-5-methyl ester-1-tert-butyl ester. According to the application, the tertiary butyl-2, 2, 2-trichloroacetic acid imine ester is used for carrying out the tert-butyl esterification reaction, so that the yield is high, the reaction condition is mild, the post-treatment is simple, the control on the generation of glutamic acid, pyroglutamic acid and pyroglutamic acid tert-butyl ester is facilitated, and the impurities are few.

The invention provides a synthesis method of a medical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine, which comprises the following steps: step S1, trans-4-hydroxy-D-proline methyl ester hydrochloride is used as a raw material, under the action of triethylamine, a reaction is carried out for 2-4 hours, and the reaction product is subjected to post-treatment to obtain the (3R, 5R)-3-Boc-amino-5-fluoropiperidine. Dichloromethane is used as a solvent to react with triphenylchloromethane to obtain (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester; s2, the (4S)-4-hydroxy-1-(triphenyl methyl)-D-proline methyl ester is subjected to oxidation, and 4-oxy-1-(triphenyl methyl)-D-proline methyl ester is obtained; s3, enabling the compound 4-oxo-1-(triphenyl methyl)-D-proline methyl ester to react with hydroxylamine hydrochloride, so as to obtain a compound hydroxylamino-1-(triphenyl methyl)-D-proline methyl ester; step S9, the compound (3R, 5R)-3-Boc amino-1-triphenyl-5-fluoropiperidine is subjected to Trt removal under the action of hydrochloric acid, and a compound (3R, 5R)-3-Boc amino-5-fluoropiperidine is obtained; according to the method disclosed by the invention, the (3R, 5R)-3-Boc amino-5-fluoropiperidine can be efficiently and economically synthesized by optimizing a reaction route.

The invention discloses a synthetic method of 1, 2, 4-triazole-3-carboxylic acid methyl ester, and belongs to the field of organic synthesis. The preparation method comprises the following steps: by taking formamidine acetate, hydrazine hydrate and dimethyl oxalate as raw materials, carrying out one-pot reaction to obtain the 1, 2, 4-triazole-3-carboxylic acid methyl ester. Compared with the prior art, the method has the advantages of short synthesis process route, short reaction time and simplicity in operation; and the synthesis process is few in three wastes, environment-friendly and green. Meanwhile, the synthesis process is safe and reliable, reaction conditions are mild, and dangerous processes such as diazotization and desulfurization are not involved.

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.

Provided is the pharmaceutical use of (3-amino-5-ethyladamantan-1-yl) methyl nitrate and a pharmaceutically acceptable salt thereof. In the present invention, provided is the use of (3-amino-5-ethyladamantan-1-yl) methyl nitrate and a pharmaceutically acceptable salt thereof in the prevention or treatment of a stroke and a sequela thereof, as well as the use in the preparation of a corresponding drug.

A process for the preparation of sphingosine 1-phosphate (11a) or a stereoisomer thereof, comprising the steps: (a) Conversion of L-serine (1a) to methyl ester (2a) or a salt thereof: (b) protecting the amino function of methyl ester (2a) or the salt thereof to form methyl ester (3a),: where Pg stands for a protecting group, (c) protecting the primary hydroxyl group and the amino group of methyl ester (3a) to form methyl ester (4a), where R 1 and R 2 independently of one another can be hydrogen, an optionally substituted C1-C6 alkyl radical or an optionally substituted phenyl radical, or wherein R 1 and R 2 together can form an optionally substituted C4-C7 cycloalkyl radical (d) Reduction of methyl ester (4a) to form alcohol (5a): (e) Oxidation of alcohol (5a) to form aldehyde (6a): (f) Reaction of aldehyde (6a) with 1-pentadecyne and a base to form alkyne (7a): (g) partial deprotection of alkyne (7a) to form alkyne (8a): (h) Reducing the triple bond of alkyne (8a) to a trans double bond to form alkene (9a): (i) Phosphorylating the primary hydroxyl group of alkene (9a) to form phosphate (10a): and (j) Deprotection of phosphate (10a) to form sphingosine 1-phosphate (11a): wherein the method has at least one of the following features: Oxidation of alcohol (5a) to form aldehyde (6a) using oxalyl chloride, DMSO and less than 5.5 equivalents of Hünig base, Oxidation of alcohol (5a) to form aldehyde (6a) at a temperature above -70°C, Reacting aldehyde (6a) with 1-pentadecyne and a base to form alkyne (7a) using at least 1.5 equivalents of 1-pentadecyne and / or Purification of the alkyne (7a), which is obtained after reacting aldehyde (6a) with 1-pentadecyne and a base to form alkyne (7a), by distilling off unreacted 1-pentadecyne.

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 present invention provides a preparation method of tozasertib, which relates to the technical field of medicine. The preparation method provided by the present invention comprises the following steps: (1) reacting methyl 2-cyanoisonicotinate with hydrazine hydrate, and crystallizing to obtain intermediate TPS-1; (2) reacting 4-cyanopyridine with a base, and then reacting completely with TPS-1, followed by filtration, washing and drying to obtain TPS-2a; (3) subjecting TPS-2a to a cyclization reaction with a reaction solvent, and after the reaction is complete, mixing with a crystallization solvent to obtain the product TPS. The product obtained by this process has a relatively high yield, with the highest total yield being about 62%, high purity, with a purity greater than 99.9%; the preparation method is simple, under the conditions of this preparation method, the raw materials react quickly, and at the same time, time-consuming operations such as extraction and concentration are avoided, and the product can be directly obtained by filtration after the reaction, with a short production cycle; the reaction conditions are easy to realize industrial operation.

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.