507 results about "Metaclazepam" patented technology

The present invention provides a pharmaceutical composition for use in a dosage form for oral administration to a patient. The composition expands upon contact with gastric fluid and promotes retention of the dosage form in the patient's stomach for a prolonged period of time. The present invention further provides pharmaceutical dosage forms containing an active ingredient, and the pharmaceutical composition. The forms are adapted for immediate or controlled release of the active ingredient. The dosage forms may be used advantageously in the treatment of Parkinson's disease with levodopa and hyperactivity and attention deficit disorder with methylphenidate.

The invention concretely relates to a synthetic technology for pyraclostrobin. The synthetic technology comprises: firstly performing cyclization to obtain 1-(4-chlorophenyl)-pyrazol-3-one, oxidizing the pyrazol ring under the effect of an oxidant to generate 1-(4-chlorophenyl)-3-hydroxypyrazole, then using 2-nitrobenzyl bromide to performing etherification to generate 1-(4-chlorophenyl)-3-[2-(nitrophenyl)methoxy]-1H-pyrazole, then using a reducing agent to perform nitro reducing, so as to generate N-hydroxyl-2-[N'-(4-chlorophenyl)pyrazol-3'-yloxymethyl]aniline, then using ClCO2CH3 to perform N-acylation reaction to generate methyl N-hydroxyl-N-2-{[N'-(4-chlorophenyl)pyrazol-3'-yloxymethyl]phenyl}formate, and finally performing hydroxyl methylation under an alkaline condition to generate pyraclostrobin. The technology enables all operations in the pyraclostrobin preparation process to be relatively controllable, helps to improve the stability of the preparation process and improve the product yield, successfully employs low-cost reagents and substantially reduces production cost, and also the employed reagents are relatively small in toxicity, is relatively beneficial for environment protection, and has no corrosivity on plastic pipes, so that the production safety is improved.

The invention discloses a preparation method for tazobactam. The preparation method comprises the following steps: with benzhydryl s-oxopenicillanate as a raw material, successively carrying out thermal cracking, bromination, catalytic oxidation and a reaction with 1H-1,2,3-triazole under the action of an anion resin carrier so as to obtain an important intermediate 2beta-(1H-1,2,3-triazolyl)-2alpha-methyl-benzhydryl penicillanate-1beta-oxide; and carrying out potassium permanganate oxidation and then protective group removal under the action of meta-cresol so as to obtain the target product tazobactam. The invention is characterized in that a sulfur atom is subjected to monooxidation so as to improve compound stability, then a nucleophilic substitution reaction with 1H-1,2,3-triazole is carried out so as to effectively control the possibility of ring enlargement during introduction of a triazole ring, and total yield is increased to 68%. The preparation method has the advantages of stable process, simple and convenient operation, easy separation and purification of the reaction product, a small amount of waste gas, waste water and industrial residues, high yield and suitability for clean, industrial and large-scale production.

Disclosed herein are mixed metal-organic frameworks, Zn₃(BDC)₃[Cu(SalPycy)] and Zn₃(CDC)₃[Cu(SalPycy)], wherein BDC is 1,4-benzenedicarboxylate, CDC is 1,4-cyclohexanedicarboxylate, and SalPyCy is a ligand of the formula:

These are useful for applications such as selective gas storage, selective molecular separations, and selective detection of molecules, including enantioselective applications thereof.

The present invention is related to a novel process for the preparation of amisulpride (I) which involves: methylation of 4-amino-salicylic-acid (VI) with dimethyl sulphate and base, optionally in presence of TBAB to obtain 4-amino-2-methoxy methyl benzoate (VII) and (ii) oxidation of 4-amino-2-methoxy-5-ethyl thio benzoic acid (IX) or 4-amino-2-methoxy-5-ethyl thio methyl benzoate (X) with oxidizing agent in the presence of sodium tungstate or ammonium molybdate to give 2-methoxy-4-amino-5-ethyl-sulfonyl benzoic acid (IV) or 2-methoxy-4-amino-5-ethyl-sulfonyl methyl benzoate (XI) respectively.

The invention belongs to the technical field of medicine, and discloses a preparation method of (3S,2'S), (3S,2'R), (3R,2'R) and (3R,2'S) four type chiral monomers of muscarine receptor antagonist racemic medicine glycopyrronium bromide. The method comprises the following steps: resolving racemic alpha-cyclopentylmandelic acid by a chemical resolution method by using L-Tyrosine methyl ester and (R)-alpha-phenylethylamine as resolution reagents to respectively prepare (S)-alpha-cyclopentylmandelic acid and (R)-alpha-cyclopentylmandelic acid; and carrying out esterification reaction to respectively obtain chiral intermediates (S)/(R)-alpha-cyclopentylmethyl mandelate. L/D-malic acid used as the raw material is subjected to four reaction steps, including condensation, carbonyl reduction, catalytic hydrogenation or transfer hydrogenation reduction debenzylation, and reduction alkylation or alkylogen alkylation, in a chiral synthesis mode to obtain another important chiral intermediate (S)/(R)-N-methyl-3-hydroxypyrrolidine. The chiral intermediate is subjected to ester exchange and quaterisation to respectively obtain the four (3S,2'S), (3S,2'R), (3R,2'R) and (3R,2'S) type glycopyrronium bromide chiral monomers. The result indicates that the (3R,2'S)-glycopyrronium bromide has the strongest cholinergic antagonistic action.

The present invention relates to a synthesis method of high-purity amlodipine besylate. In particular, o-chlorobenzaldehyde, 4-(2-phthalyl imino radical ethoxy) acetoacetic ester and 3-amino methyl cro-tonate are used as raw materials for ring closure in an alcohol solvent, and when the amount of the 3-amino methyl cro-tonate is three times, the intermediate for ring closure can be prepared; the intermediate is refined by toluene/glacial acetic acid, dissolved in methylamine to form a salt in the aqueous solution, and the high-purity amlodipine besylate can be acquired after recrystallization with ethyl alcohol.

The invention discloses a method for preparing progesterone by taking 1,4-androstenedione as a raw material, which comprises the following steps: 1) dissolving 1,4-androstenedione into an organic solvent, adding the acid of trimethyl orthoformate or triethyl orthoformate, and introducing nitrogen to protect the 1,4-androstenedione to synthesize the enol ether of 1,4-androstenedione, namely 3-methoxy-androstane 3,5-diene-20-ketone; and 2) dispersing (1-methoxy ethyl)-triphenylphosphine salt in a reaction medium, an organic solvent, adding alkali at low temperature, performing a Wittig reaction of the 3-methoxy-androstane 3,5-diene-20-ketone synthesized in the step 1), and purifying and crystallizing to obtain progesterone. By adopting the 1,4-androstenedione as the raw material, the method solves the problem that of lack in raw materials for synthesizing steroid drugs such as progesterone, and improves the utilization rate of 1,4-androstenedione and the yield of progesterone; the preparation process is simple.

The present invention relates to novel azoles, novel antiviral active components of the general formulas 1A and 1B, pharmaceutical composition, antiviral medicament, method for prophylaxis and treatment of viral diseases, particularly caused by hepatitis C viruses (HCV). In general formulas 1A and 1B

wherein: solid lines with accompanying dotted lines () represent ordinary bond or double bond, provided that one of them is an ordinary bond, the other one is double bond; X and Y accept various meanings, one of them is—nitrogen, the other—oxygen, sulfur or NH group; R¹ and R²—optionally the same radicals selected from 2-(R)- and (S)-substituted N-acyl pyrrolidine derivatives; N-methyl-N-[2-(R) and (S)-substituted 2,2-disubstituted acetamides; methyl[2-(R) and (S)-substituted ((methyl)amino)-(1-oxobutan-2-yl)-2-(R)-] and (S)-iso-propyl)-carbamates. A represents aliphatic C₂-C₈ biradical; dioxane, cyclo- and bicycloaliphatic, alkyloxyalkyl, alkyloxyalkylenoxyalkyl, alkenyloxyalkyl, alkynyloxyalkyl biradicals and their thioanaloges; aryl and thiophene alkynylcycloalkyl, alkynyldioxane, alkynylaryl, alkylthiophene, alkenylthiophene and alkynylthiophene, alkyloxyaryl, alkenyloxyaryl, alkynyloxyaryl, alkylthioaryl, alkenylthioaryl, alkynylthioaryl, cycloalkylthiophene, aryldioxane and thiophenyldioxane biradicals. B represents: aliphatic C₂-C₈ radical, including 1, 2 or 3 triple C≡C bonds; aryl and thiophene, alkynylcycloalkyl, alkynyldioxane, alkynylaryl, alkylthiophene, alkenylthiophene and alkynylthiophene, cycloalkylbenzene, 4-cycloalkylbiphenyl, bicycloalkylbenzene, 4-bicycloalkylbiphenyl, cycloalkylthiophene, aryldioxane and thiophenyldioxane radicals.

The invention belongs to the field of medicinal chemistry, and discloses a technology for preparing aclidinium bromide. By adopting the technology, (R)-3-quinuclidinol, (C1)methyl-2,2-dithienyl glycolate and 3-phenoxy propyl bromide are taken as raw materials, and the aclidinium bromide is prepared by adopting a one-pot process. The method is simple to operate, and convenient for post-treatment, and has good application value.

The invention discloses a preparation method of an intermediate of an anti-new crown drug Paxlovid. According to the preparation method, cheap and easily available N-Boc-trans-4-hydroxy-L-proline methyl ester (compound II) is taken as an initial raw material, the Paxlovid intermediate can be obtained through a plurality of steps of reactions, and the structural formula of the anti-new crown drug Paxlovid intermediate is as shown in the formula I. The method has the advantages of simple process, low production cost, easiness in industrial production and the like.

The invention relates to an amlodipine besylate compound and a novel preparation method thereof, wherein the method comprises the following steps that: a moderate amino-protecting reagent of di-tert-butyl dicarbonate is adopted so that the introduction of a Boc protecting group is realized, through the reaction of intermediums of 3-amino-crotonic acid methyl ester and 2-chlorobenzaldehyde, the obtained amlodipine besylate compound is directly carried out BOC protecting group removal reaction with benzene sulfonic acid, and the final product is obtained. Consequently, the invention is dispensed with the special deprotection step, simplifies the reaction steps, is more suitable for industrialized production and has high total reaction yield.

The invention relates to a preparation method of a compound represented by the formula (i); and the compound represented by the formula (i) is prepared by taking glycine methyl ester or hydrochloride thereof as the starting material through benzaldehyde protection, benzyl chloride biphenyl alkylation and deprotection. According to the invention, the starting material is easy to obtain and low in cost; furthermore, an intermediate related in the reaction process is unnecessary to separate and purify; the preparation method is simple to operate and moderate in reaction condition; and therefore, the preparation method is applied to industrialized mass production.

The invention relates to a synthesis method of bulk drug of anagliptin for treating II type diabetes, and aims to solve the problem that at present there is no industrial synthesis method of anagliptin. The synthesis method comprises the following steps: (1) taking vinyl ethyl ether and trichloroacetic chloride as the raw materials, carrying out three-step reactions to obtain an intermediate (4) with a protected aldehyde group; carrying out dehydration condensation between the intermediate (4) and 3-amino-5-methylpyrazole to obtain pyrazolopyrimidine parent nucleus; and hydrolyzing carboxyl ethyl ester to obtain 2-methyl-pyrazolo[1,5-a]pyrimidine-6-carboxylic acid6; (2) taking L-proline as the raw material, subjecting L-proline to methyl esterification, ammoniation, acetylation, and cyaniding reactions to obtain a chiral cyanopyrrole intermediate (11); making the chiral cyanopyrrole intermediate (11) and a diamine segment (12) carry out nucleophilic substitution reactions under an alkaline condition to obtain an intermediate (13), and finally removing the Boc protective group from the intermediate (13) in the presence of hydrochloric acid to obtain a cyanopyrrole amine intermediate (14); (3) coupling 2-methyl-pyrazolo[1,5-a]pyrimidine-6-carboxylic acid 6 with the cyanopyrrole amine intermediate (14) under condensation conditions so as to obtain the bulk drug anagliptin.

The present invention provides an oxiracetam drug activity composition, which comprises the following components: a component I, a component II and a component III, wherein the component I is oxiracetam, the component I content is more than or equal to 98.0%, the component II is glycine anhydride, the component II content is more than 0 and is less than or equal to 0.3%, the component III is one or a plurality materials selected from 4-hydroxy-2-oxo-1-pyrrolidineacetic acid, 4-hydroxy-2-oxo-1-pyrrolidine, ethyl 4-hydroxy-2-oxopyrrolidine-1-acetate, methyl 4-hydroxy-2-oxopyrrolidine-1-acetate, and piracetam, the component III content is more than 0 and is less than or equal to 1.5%, the 4-hydroxy-2-oxo-1-pyrrolidineacetic acid content is more than 0 and is less than or equal to 0.5%, and the total content of the component II and the component III is less than or equal to 1.5%. The drug activity composition of the present invention has stable quality, and can completely meet quality requirements on the drug activity composition by oxiracetam preparations. In addition, the prepared preparation has characteristics of safety, effectiveness, and controllable quality, and clinical therapy effects and medication safety of the oxiracetam preparation are ensured.

The invention relates to a synthesizing method of 2-amino-5,8-dimethoxy[1,2,4]-triazolo[1,5-c]-pyrimidine. The invention solves the problems such as low yield, high pollution, complicated operation, and the like of current preparation methods. The method provided by the invention comprises the steps that: methoxy methyl acetate and methyl formate are condensed under a strong-alkali condition; the condensation product is subjected to cyclization with thiourea; methylation is carried out by using chloromethane; chlorination is carried out by using phosphorus oxychloride; hydrazination is carried out by using hydrazine hydrate; the product is subjected to cyclization with cyano bromine; and under the effect of strong alkali and acrylate, a final product is obtained. With the method provided by the invention, the yield of each step is higher than 80%, and a total yield reaches 39%. The method is suitable for industrialized productions. The method provided by the invention belongs to the field of paddy rice herbicide penoxsulam intermediate preparation.

The invention discloses a high selectivity method for synthesizing moxifloxacin. The method comprises the following steps of: reacting boric anhydride with trifluoro acetic anhydride to obtain a chelant; reacting 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid ethyl ester with the chelant, cooling to room temperature, adding ice water, performing suction filtration, and washing a filter cake with water until neutrality to obtain a 1-ethyl-7-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid methyl ester trifluoroacetic anhydride boronized chelate; and reacting the 1-ethyl-7-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid methyl ester trifluoroacetic anhydride boronized chelate with (S,S)-2,8-diazabicyclo[4,3,0]nonane to obtain a 1-cyclopropyl-6-fluoro-7-([S,S]-2,8-diazabicyclo[4,3,0]nonane-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid ethyl ester trifluoroacetic anhydride boronized chelate, recycling a solvent under reduced pressure, adding alkali, refluxing, discoloring, filtering, freezing, performing suction filtration, and drying a filter cake. The method is simple, mild in conditions, and high in selectivity, avoids difficultly separated impurities, is high in reaction yield and product purity, and is suitable for industrial production.

The invention discloses a lysine-modified benzofuroxan compound, a synthetic method, an application and a recovery method of the lysine-modified benzofuroxan compound as well as a method of detecting the concentration of copper ions. The structural formula of the lysine-modified benzofuroxan compound is shown in the specification. The synthetic method of the lysine-modified benzofuroxan compound comprises the following steps: 1) carrying out reaction on methanol, thionyl chloride and lysine to obtain lysine methyl ester hydrochloride; 2) in the presence of an acid binding agent, carrying out reaction on the lysine methyl ester hydrochloride and 4-chlorine-7-nitro-benzofuroxan, and carrying out column chromatography; and 3) dissolving the product obtained in the last step in alkali liquor, extracting for multiple times, regulating a pH value of a water phase, extracting for multiple times, collecting an extractant layer, and carrying out purification. The method of detecting the concentration of the copper ions comprises the following steps: 1) drawing a standard curve; 2) detecting and recording; and 3) carrying out calculation. The recovery method of the lysine-modified benzofuroxan compound comprises the following steps: adding a complexing agent aqueous solution into the compound solution containing the copper ions, uniformly mixing, extracting, collecting an organic phase, and removing a solvent. The lysine-modified benzofuroxan compound is applied to preparing a copper ion fluorescent probe. The synthesized lysine-modified benzofuroxan compound is capable of specifically detecting the copper ions, can be prepared into the probe and can also be recovered.

The invention provides high-stability moisture preservation sun-screen cream, which is prepared from cyclopentasiloxane, cyclohexasiloxane, titanium dioxide, caprylic/capric triglyceride, C12-15 alcohol benzoate, CI 77891, PEG-30 dihydroxy stearate, polydimethyl siloxane crosslinked polymers, ethylhexyl methoxycinnamate, disteardimonium hectorite, propylene garbonate, cetyl dimethicone, stearoyl inulin, tocopheryl acetate, bis-PEG/PPG-14/14 polydimethylsiloxane, cetyl PEG/PPG-10/1 polydimethylsiloxane, cyclopentasiloxane, PEG/PPG-18/18 polydimethylsiloxane, sucrose polyoleate, butanediol, propanediol, sodium chloride, 1,2-hexanediol, 1,2-pentanediol, allantoin, EDTA-disodium, butanol polyether-3, azimino-benzene butyl sodium phenolsulfonate, tributyl citrate, lycine, sodium hyaluronate, niacinamide, creatin, methyl hydroxybenzoate, peony root extracts, rice fermentation product filter liquid and phenoxyethanol. The formula design is reasonable; the irritation is small; the stability ishigher than that of a conventional sun-screen cream; the sun-screen and moisture preservation effects are ensured; the formation of free radicals is reduced; the anti-aging function is achieved.

The invention belongs to the technical field of medicine and discloses a preparation method of muscarinic receptor antagonist glycopyrronium bromide. The preparation method of the muscarinic receptor antagonist glycopyrronium bromide is characterized in that Alpha-cyclopentyl mandelic acid methyl ester is obtained by aceptophenone ketonic acid Grignard reaction and esterification reaction, and then glycopyrronium bromide is obtained by N-methyl pyrrolidine-3-alcohol ester exchange and quaterisation.

The invention relates to an intermediate for preparing azilsartan and a novel preparation method for the azilsartan. The method includes the following steps: 1) reducing 2-cyano-4'-bromomethylbiphenyl with hydroxylamine hydrochloride to generate (Z)-4'-bromomethyl-(N')-hydroxy-[1,1'-biphenyl]-2-amidine; 2) performing esterification with ethyl chloroformate to generate (Z)-4'-bromomethyl-(N')-((ethoxycarbonyl)oxyl)-[1,1'-biphenyl]-2-amidine; 3) performing ring closing to prepare 3-(4'-(bromomethyl)-[1,1'-biphenyl]-2-yl)-1,2,4-oxadiazole-5-(4H)-one; 4) performing a condensation reaction to 2-ethoxy-1H-benzimidazole-7-methyl carboxylate and the 3-(4'-(bromomethyl)-[1,1'-biphenyl]-2-yl)-1,2,4-oxadiazole-5-(4H)-one to prepare 2-ethoxy-1-((2'-(2,5-dihydro-5-oxy-1,2,4-oxadiazole-3-yl)biphenyl-4-yl)methyl)benzimidazole-7-methyl carboxylate; and 5) finally performing hydrolysis to prepare the azilsartan. The method employs the raw material being easy to obtain, is short in synthetic route, is low in device cost, is less in side products, is low in toxicity and pollution, is environment-friendly, is high in product purity and is suitable for industrial production.