224results about "Organic racemisation" patented technology

The invention provides a chiral resolution method and application of a 3-aryl substituted glutaric acid monoester compound, and the method comprises the following steps: taking a substance as shown in a formula I as a starting raw material, and carrying out alcoholysis to obtain a racemic intermediate as shown in a formula IV; and splitting the intermediate shown in the formula IV, and then dissociating to obtain the compound shown in the formula III, which has a single spatial configuration and an ee value of more than 99%. A cyclic anhydride substrate with a symmetrical structure is used and reacts with alcohol to obtain racemic 3-aryl substituted glutaric acid monoester, a target configuration with high chiral purity is obtained by screening some resolution reagents and solvents and performing salifying resolution on the 3-aryl substituted glutaric acid monoester, the operation is simple, the resolution reagents are easily available in the market and can be recycled, and the method is suitable for industrial production. The method has the advantages that an expensive chiral catalyst or a harsh enzyme catalysis condition is avoided, the reaction cost is reduced, amplified production is facilitated, the ee value of a target configuration can be increased to 99% or above, and the method is an economic and environment-friendly technical route which is simple in post-treatment and convenient for amplified production.

The invention discloses a preparation method of four new skeleton alkaloid compounds with anti-inflammatory effect in the root of Anachymin and the use of the anti-inflammatory activity thereof. The four new skeleton alkaloid compounds are extracted from the root (root of Anachymin) of Roman pyrethrum (Anacyclus pyrethrum (L.) DC.) by using an organic solvent, and then separated by two or three methods of normal phase silica gel column chromatography, reverse phase silica gel column chromatography and semi-preparative high performance liquid chromatography to obtain eight new skeleton alkaloid monomer compounds, and the structures thereof are identified by high-resolution mass spectrometry, nuclear magnetic resonance spectroscopy and X-ray single crystal diffraction. The invention also provides the NO inhibition effect of these compounds.

The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structureuseful for the synthesis of compounds that target KRAS G12C mutations, such as

The invention discloses a chiral amine reagent and a preparation method thereof as well as a method for analyzing and splitting a chiral drug, the chiral amine reagent is APMA # imgabs0 # or d5-APMA # imgabs1 #, and the configuration of a carbon atom connected with an amino group on a piperidine ring in the structural formula is an S configuration. The APMA and d5-APMA provided by the invention can be used for analysis and detection of chiral drugs, 3-aminocyclohexyl-phenyl methane ketone (APMA) and the d5-APMA in a stable isotope form thereof are independently or jointly used as a pair of isotope labeling reagents and are subjected to condensation reaction with the chiral drugs to obtain derivatives, enantiomers of the chiral drugs can be effectively split, and the chiral drugs can be analyzed and detected. And an easy-to-ionize group is introduced, so that the mass spectrum response in an ESI positive ion mode is greatly improved.

The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structureuseful for the synthesis of compounds that target KRAS G12C mutations, such as

The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structureuseful for the synthesis of compounds that target KRAS G12C mutations, such as

The invention relates to a method for preparing S-citalopram based on an R-diol intermediate. The method comprises the following steps: (1) carrying out SN2 configuration inversion on a citalopram R-diol intermediate under the action of a large-steric-hindrance acid and a large-steric-hindrance ligand to obtain a mixture containing S-citalopram and R-citalopram; and (2) obtaining the S-citalopram from the mixture in the step (1) under the action of a resolving agent. In addition, the invention also discloses a preparation method of the S-citalopram. The optical purity of the S-citalopram prepared by the method is greater than 95%, and the optical purity is greater than 99% after the S-citalopram is purified. In addition, the total yield of S-citalopram is increased to 82% from 31% in the prior art.

The present invention relates to a process for preparing acyloxymethyl esters of (4S)-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid of the formula (IIa) by optical resolution of the compound of the formula (II) using a hydrolase. The invention also relates to a process for preparing (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula (Ia), wherein the process comprises the optical resolution of the compound of the formula (II) using a hydrolase. The invention additionally also relates to the use of a hydrolase in a process for preparing a compound of formula (IIa). The invention further relates to the use of a hydrolase in a process for preparing a compound of formula (Ia).

The application provides a preparation method of finerenone and intermediates thereof. The application discloses a preparation method of a finerenone intermediate 5, which comprises the following steps: step 1: in an organic solvent, a resolution reaction is carried out between a finerenone intermediate 2 and D-tartaric acid diphenyl ester to obtain a resolution salt, then an acid-base reaction is carried out between the resolution salt and a base to obtain the finerenone intermediate 3; step 2: in an organic solvent, a nucleophilic substitution reaction is carried out between the finerenone intermediate 3 and triethyl orthoformate in the presence of an acid to obtain a finerenone intermediate 4; step 3: in a solvent, a hydrolysis reaction is carried out between the finerenone intermediate 4 to obtain the finerenone intermediate 5. The preparation method has the advantages of short reaction steps, high total reaction yield, simple and safe operation, simple post-treatment steps, high product purity, low production cost and suitability for industrial production.

The invention relates to the technical field of medicines, in particular to a preparation method of calcium L-5-methyltetrahydrofolate. According to the method, N-(4-aminobenzoyl)-L-glutamic acid, 2, 4, 5-triamino-6-hydroxypyrimidine sulfate and propane trihalide are adopted as starting raw materials, and tetrahydrofolic acid is synthesized through a one-pot method; compared with synthesis of L-5-methyl calcium tetrahydrofolate by using high-purity folic acid as an initial raw material, the process route does not involve use of chemical reagents such as sodium borohydride, zinc powder and some noble metal catalysts any more, the reaction is easier to control, the cost is lower, the safety is higher, the method is more environmentally friendly, and industrial production is easier to carry out.

The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structureuseful for the synthesis of compounds that target KRAS G12C mutations, such as

The invention provides a method for regulating and controlling dynamic kinetic resolution of spiral polycyclic aromatic hydrocarbon based on an inorganic chiral surface and application, and the method comprises the following steps: S1, rotating a substrate clockwise or anticlockwise, and depositing an inorganic material on the substrate by adopting a physical vapor deposition method to obtain an inorganic chiral nano material layer; wherein the contact angle between the inorganic material and N, N-dimethylformamide is less than 22 degrees, and the deposition angle and the normal direction of the substrate form an angle of 86 degrees or 0 degree; s2, dissolving spiral polycyclic aromatic hydrocarbon molecules needing to be split into N, N-dimethylformamide to obtain a solution; then dropwise adding to the surface of the inorganic chiral nano material layer to obtain a sample; and S3, annealing the sample at 40-50 DEG C, and obtaining the homochiral aggregate after the solvent is completely evaporated. The technical scheme provided by the invention is high in controllability, strong in universality and good in stability, and can be used for efficiently preparing chiral compounds with specific configurations.

To provide a simple method for optically resolving a chiral compound, which is expected to be industrially applicable.SOLUTION: A method for optical resolution of a chiral compound includes dissolving a mixture of both enantiomers of the chiral compound in a first solvent to prepare a first solution, stirring the prepared first solution, precipitating a first gel in the stirred first solution, and separating the first solution into the first gel and a first supernatant.SELECTED DRAWING: Figure 1

The invention discloses an alkaloid compound extracted from anacyclus pyrethrum (L.) DC. As well as an extraction method and application thereof. The alkaloid compound is extracted from the anacyclus pyrethrum (L.) DC. Root (L.) by adopting an organic solvent, and the extraction method comprises the following steps: extracting the alkaloid compound from the anacyclus pyrethrum (L.) DC. And separating by using two, three or four combined methods of normal-phase silica gel column chromatography, reverse-phase silica gel column chromatography and semi-preparative high performance liquid chromatography to obtain the novel skeleton alkaloid compound. In addition, the compounds provided by the invention can play an anti-inflammatory role by inhibiting nitric oxide (NO) of cells, so that the compounds can be used for preparing anti-inflammatory drugs.

The invention discloses an enantiomer crystallization resolution method of delta-dodecalactone, which comprises the following steps: hydrolyzing delta-dodecalactone under an alkaline condition for ring opening, acidifying to obtain 5-hydroxylauric acid, adding a dehydroabietylamine solution, dissolving in an alcohol solvent or a solvent system consisting of the alcohol solvent and other solvents, fully reacting, cooling, slowly crystallizing, filtering, washing, and drying to obtain the delta-dodecalactone enantiomer. Filtering, adding ethyl acetate and hydrochloric acid into a filter cake for dissolving, carrying out liquid-liquid extraction and washing an organic phase, and carrying out rotary evaporation concentration on the organic phase to obtain optically enriched delta-dodecalactone; the method is simple to operate and does not depend on expensive special equipment, and the sample loading amount is greatly increased; due to the introduction of dehydroabietylamine, the 5-hydroxylauric acid and the dehydroabietylamine form diastereoisomer salt, and chiral separation is carried out in the crystallization process; the reaction safety is high, and the requirements of green chemistry are met.

To provide arylcyclohexylamine compounds and their use in the treatment of psychiatric disorders.SOLUTION: There are provided arylcyclohexylamine compounds and compositions of a single enantiomer or enantiomerically enriched mixtures of arylcyclohexylamine having significantly higher oral bioavailability, higher antidepressant potency, and / or greater therapeutic index between antidepressant effects and side effects, compared to ketamine.SELECTED DRAWING: None

The present invention belongs to the field of drug splitting technology, and in particular to a method for splitting ofloxacin chiral drugs by two-phase identification extraction. The present invention mixes ofloxacin racemate, cyclodextrin and water to obtain ofloxacin racemate aqueous phase solution; Cyclodextrin includes β-cyclodextrin and / hydroxypropyl β-cyclodextrin, and the mass concentration of cyclodextrin in ofloxacin racemate aqueous phase solution is 0.005~0.015g / mL; Tartaric acid and organic solvent are mixed to obtain organic phase solution; Tartaric acid includes L / D-di-p-methylbenzoyltartaric acid, L / D-dibenzoyltartaric acid and L / D-diethyl tartrate; Ofloxacin racemate aqueous phase solution and organic phase solution are mixed, and the obtained mixed solution is subjected to chiral extraction. The splitting method provided by the present invention not only has higher selectivity, and low cost, is suitable for industrial application.

The present invention discloses a method for converting a chiral compound racemate into a single enantiomer, combining crystallization and SMB processes, while reducing the separation purity requirements of SMB, respectively, the chiral substance solution at the SMB extraction port and the raffinate port is crystallized and purified, and in addition, an equal mixture of the racemate raw material, the product of the racemization reaction of the single enantiomer derived from the non-target product in the racemization reactor, and the eutectic generated by the two crystallizers is used as the three sources of the racemate at the SMB feed port, which can not only ensure the purity of the target product, but also achieve high utilization of the racemate raw material and high yield of the target product, while significantly improving the overall equipment yield. It can be seen that using the method of the present invention, the chiral compound racemate can be converted into a single enantiomer, which can significantly improve the overall equipment yield while ensuring the purity and yield of the target product.

A process is provided for the formation of high purity magnesium L-lactate crystals from homogeneous and heterogeneous decomposed organic wastes. The process provides magnesium L-lactate crystals with improved enantiomeric and overall purity that are particularly suitable for reuse in the production of new polylactic acid.

This invention provides a method for preparing chiral epoxy compounds, chiral β-lactones, and polyhydroxyalkanoates. The method involves three steps: chiral resolution of the epoxy compound, carbonylation of the chiral epoxy compound to prepare a chiral β-lactone, and ring-opening polymerization of the β-lactone. Using this method, polyhydroxyalkanoates with good tensile strength and toughness, as well as a wide processing window, can be prepared. This invention has advantages such as simple steps, low raw material costs, and no need to introduce a second monomer, making it easy to scale up production.

A composition of a crystalline form salt or polymorph of R-MDMA. A pharmaceutical composition of a crystalline salt or polymorphic substance of R-MDMA and a pharmaceutically acceptable excipient. A method of treating a medical condition in a subject by administering to the subject an effective amount of a composition of a crystalline form salt or polymorph of R-MDMA and treating the subject.

The invention relates to the technical field of chiral stationary phase fillers, in particular to an underived beta-cyclodextrin chiral stationary phase as well as a preparation method and application thereof. Underived beta-cyclodextrin is bonded on the surface of silica gel through urea or thiourea groups respectively, and the structure is shown as a formula I in the specification. The preparation process of the underived beta-cyclodextrin chiral stationary phase filler provided by the invention has the advantages of simple and easily-controlled conditions, no need of complex derivatization and good repeatability. The novel chiral stationary phase is suitable for different mobile phase systems of high performance liquid chromatography, can efficiently separate N-containing chiral compounds such as imidazole antibacterial drugs and triazole pesticides in various structure types, and can meet the requirements of daily analysis, production process and use process quality control and the like of the chiral drugs and the chiral pesticides.

This invention belongs to the field of recycling and purification technology, specifically relating to a method for recovering the β isomer from a CME solution containing both β and α isomers. The method includes the following steps: concentrating the CME solution containing both β and α isomers and dissolving it in methanol with trichloroacetic acid to form a salt, followed by cooling and crystallization and filtration to obtain the trichloroacetic acid salt of the CME β isomer; then, ionizing the trichloroacetic acid salt of the CME β isomer in methanol with ammonia to obtain the CME β isomer. By reacting trichloroacetic acid with the α and β isomers of CME to form a salt, the different solubilities of the trichloroacetic acid salts of the α and β isomers are utilized to separate the trichloroacetic acid salt of the CME β isomer, and then ionizing the trichloroacetic acid salt of the CME β isomer with ammonia, the CME β isomer is recovered.

The invention relates to processes for preparing carbaprostacyclin analogues and intermediates prepared from the processes. The invention also relates to cyclopentenone intermediates in racemic or optically active form.

The present invention relates to a preparation method for tert-butyl (R)-3-amino-1-oxa-8-azaspiro[4.5]decane-8-carboxylate, comprising the following steps: enabling N-BOC-4-piperidone to undergo a Grignard reaction with allylmagnesium halide to obtain intermediate 1; enabling the intermediate 1 to undergo a substitution reaction with 3-halopropene to obtain intermediate 2; enabling the intermediate 2 to undergo an olefin metathesis reaction under the action of a Grubbs catalyst to obtain intermediate 3; enabling the intermediate 3 to undergo a nitration reaction with nitric acid to obtain intermediate 4; enabling the intermediate 4 to undergo a hydrogenation reduction reaction to obtain racemic intermediate 5; and enabling the intermediate 5 to undergo chiral resolution by means of a resolving agent to obtain a target product. The preparation method provided by the present invention has a short process route, simple operation, and no substantial waste water and waste gas generated, and can achieve relatively high total product yield and chemical and chiral purities.

The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure useful for the synthesis of compounds that target KRAS G12C mutations, such as

The invention discloses a high-yield synthesis method of elxalidone, and relates to the technical field of drug synthesis. 1-chloro-2-(trifluoromethyl) benzene and 4-(methylsulfonyl) aniline are used as initial raw materials; according to the present invention, the isaprorenone is obtained through the Grignard reaction, the addition reaction, the bromination reaction, the condensation reaction, the substitution reaction, the cyclization reaction, the reduction reaction, the substitution reaction and the chiral resolution, and the synthesis method has advantages of low raw material cost, short route, high yield and the like, and can be used for the quantitative production of the isaprorenone.

The invention relates to the field of organic synthesis, in particular to a synthetic method of (2R, 4S)-N-BOC-4-hydroxypiperidine-2-methyl formate. The synthesis method of (2R, 4S)-N-BOC-4-hydroxypiperidine-2-methyl formate comprises the following steps: mixing a material A, a material B, potassium carbonate, sodium iodide and a solvent, and reacting to obtain a material C; mixing the material C, the material D, triethylamine and a solvent, and reacting to obtain a material E; mixing the material E, ammonia water and a solvent, and reacting to obtain a material F; and mixing the material F, di-tert-butyl dicarbonate, a palladium carbon catalyst and a solvent, and carrying out a reaction to obtain the (2R, 4S)-N-BOC-4-hydroxypiperidine-2-methyl formate. The process route is easy to operate and has no special dangerous reaction. Reaction materials are cheap and easy to obtain, and the prepared product is high in purity.

The invention discloses a ferrocenyl chiral diphosphine ligand and a preparation method of an intermediate of the ferrocenyl chiral diphosphine ligand, and belongs to organic synthesis. The method comprises the following steps: dissolving acetylferrocene and a chiral catalyst in an organic solvent, dropwise adding dimethylamine, after the reaction is finished, purifying to obtain a crude product of N, N-dimethyl-1-ferrocenylethylamine, and splitting and dissociating to obtain (S)-(-)-N, N-dimethyl-1-ferrocenylethylamine. The preparation method comprises the following steps: dissolving 2, 4-dichlorophenoxyacetic acid into an organic solvent, dropwise adding sec-butyllithium under a low-temperature condition, continuing to react, dropwise adding an organic solvent solution of iodine under a low-temperature condition, and continuing to react to obtain an iodinated product; then carrying out Ullmann reaction on the iodinated substance under the catalysis of nickel to obtain a coupling product; and finally, dissolving the coupling intermediate and diphenylphosphine in acetic acid, and continuously reacting to obtain a target product. The preparation method provided by the invention has the advantages of cheap and easily available raw materials, less chiral catalyst dosage, less preparation steps, high product yield and good product quality.

Provided is an amine separation method that includes separating an amine through chromatography using a stationary phase including a ligand having a crown ether-like cyclic structure and being supported on a carrier; and a mobile phase containing a salt of a cation and an acid anion at a concentration of 0.2 mM or more and 50.0 mM or less and containing a solvent having a water content of 50 vol. % or less.