23 results about "HATU" patented technology

The invention discloses an omariglitazone intermediate as well as a synthesis method and application thereof, and belongs to the technical field of pharmaceutical chemistry synthesis. The invention provides a synthesis method of an omarigliflozin intermediate and application of the intermediate in synthesis of omarigliflozin. The key of the synthesis method provided by the invention lies in the deprotection process of polycyclic indole amide, nitrile groups are not hydrolyzed, indole carboxylic acid is generated with high selectivity, molecular lactamization is avoided in the condensation process with polycyclic imine B, and expensive amidation reagents such as HATU are not needed in the process, so that the synthesis method is simple and easy to implement. And the purpose of preparing omariglitazone with low cost and high yield is achieved. The synthesis method has the advantages of easily available raw materials, mild reaction conditions, small side reaction influence, simplicity and convenience in operation and high yield, improves the yield, is easy to purify, and is suitable for industrial production of omariglitazone.

The preparation method comprises the following steps: dissolving a compound 1 and a compound 2 in a certain volume of acetonitrile, adding HATU, and generating a crude product solution of the lefanacin at a certain temperature; and purifying the crude product solution of the lehanakine to obtain the high-purity lehanakine. The ratio of the volume of acetonitrile to the mass of the compound 1 is preferably (15-30) ml: 1g, the reaction temperature is preferably 25-35 DEG C, and the reaction time is longer than or equal to 2 hours. According to the present invention, the reaction solvent, the reaction temperature and the reaction time are optimized, and the amide condensation catalyst with the high activity is selected, such that the reaction efficiency of the compound 1 and the compound 2 is high, the lefanacin yield is significantly improved, and the high-purity lefanacin is obtained after purification.

The invention relates to the technical field of biological medicine manufacturing, in particular to an environment-friendly and efficient Difelikefalin preparation method. According to the method, a solid-phase peptide synthesis technology is adopted, and the core is that a green mixed solvent system composed of 2-methyltetrahydrofuran and cyclopentyl methyl ether is used for comprehensively replacing traditional toxic solvents such as DMF and DCM. The method comprises the steps of resin swelling, Fmoc deprotection, amino acid coupling, peptide chain cutting, purification and freeze drying, a piperidine / 2-MeTHF solution is adopted in the deprotection, an optimized HATU / DIPEA activation system is adopted in the coupling reaction, a TFA / 2-MeTHF / water mixed solution is adopted in the cutting, and an ethanol-water chromatographic system is adopted in the purification. According to the invention, closed-loop circulation of the solvent is also realized, and 2-MeTHF and CPME are purified through rotary evaporation and reused in the synthesis process. According to the method, high purity and high yield of the product are guaranteed, production toxicity and environmental hazards are remarkably reduced, and the method has excellent industrial application prospects.

The application relates to the technical field of drug synthesis, in particular to a synthesis method and application of a 2-(cyclopropylamide)thiazole-4-amide derivative. The thiazole structure is shown in formula I. The preparation method of the 2-(cyclopropylamide)thiazole-4-amide derivative is as follows: the compound shown in formula I is obtained by reacting the compound shown in formula II in the presence of HATU, DIPEA, a primary amine or a secondary amine and tetrahydrofuran. The 2-(cyclopropylamide)thiazole-4-amide derivative has the effect of relieving Alzheimer's disease, and is characterized by strong cholinesterase inhibition activity.

The invention discloses a fluorescent probe for recognizing lithium ions and a preparation method and application thereof.The method comprises the steps that rhodamine B, HATU and methyl 3-amino-3-methyl-1-butyrate are mixed and subjected to a first-step reaction, a first reactant is obtained, the first reactant, ethyl alcohol and sodium hydroxide are mixed and subjected to a second-step reaction, a second reactant is obtained and subjected to a third-step reaction, and the fluorescent probe for recognizing the lithium ions is obtained. And mixing the second reactant, crown ether, EDCI and HOBT, and carrying out a third-step reaction to obtain the fluorescent probe. According to the method, lithium ions in a complex environment can be efficiently recognized, and raw material waste and resource loss in the production process are avoided.

The present invention discloses a cationic nanocarrier for penetrating fibrocartilage and its preparation method and application, which belongs to the field of biomedicine technology. The preparation method comprises the following steps: mixing an ethylenediamine solution and a Boc-Lys(Fmoc)-OH solution, adding HATU and HOAt for activation, adding DIPEA for further activation, stirring the reaction, adding glacial ether and standing to obtain a precursor; mixing the precursor and a piperidine solution, adding glacial ether and n-hexane and standing to obtain DGL; reacting DGL in a mixed solution of TFA, DCM and TIS to obtain de-Boc DGL, and reacting the de-Boc DGL with phenylboronic acid in a solvent. The cationic nanocarrier prepared by the present invention can reversibly bind to glycosaminoglycans in cartilage and penetrate the full layer of condylar cartilage of the temporomandibular joint while carrying siRNA to target deep chondrocytes, giving lysosomal escape ability, promoting chondrocyte uptake, and improving siRNA transfection efficiency.

The invention discloses an anti-myocardial fibrosis compound as well as a preparation method and application thereof, and belongs to the technical field of medicine synthesis. The preparation method of the compound A comprises the following steps: adding 219 mg of DIPEA into 4 mL of an anhydrous DMF solution containing 100 mg of a compound 6 and 74 mg of a VHL ligand 7, 30 min later, adding 64 mg of HATU, stirring for 4 h at room temperature, pouring the mixture into 40 mL of water, extracting with dichloromethane, combining an organic layer, washing the organic layer with a saturated sodium chloride solution, drying with anhydrous Na2SO4, spin-drying the organic layer at 40 DEG C in vacuum, and separating with a silica gel column. The compound A and the compound B obtained in the invention can significantly reduce the levels of collagen Collagen I and Collagen III of myocardial fibroblasts, and have good anti-myocardial fibrosis effect, and the compound C, the compound D and the compound E have weak anti-myocardial fibrosis effect.

The present invention belongs to the field of pharmaceutical technology, and particularly relates to a protein degradation-targeting chimera for CPT1A, its preparation method, and application. (S,R,S)-AHPC-PEG4-NH2 HCl, etomoxir (sodium salt), and DIPEA are added to an organic solvent, followed by HATU, and the reaction is stirred at 20-25°C. After completion of the reaction, the chimera of formula (I) is obtained by purification. A new PROTAC capable of targeted degradation of the CPT1A protein was developed by linking the CPT1A inhibitor etomoxir (sodium salt) to a conjugate of the E3 ubiquitin ligase VHL ligand and a linker. This PROTAC can bind to CPT1A and trigger its effective degradation, significantly downregulating CPT1A levels, and has important application prospects in tumor treatment.

This invention belongs to the field of heterocyclic compound technology, specifically relating to a protein hydrolysis-targeted chimera for the treatment of multiple myeloma, its preparation method, and its application. Compounds 2, 3, and HATU are dissolved in THF, then DIPEA is added and the reaction is stirred. Water is added to terminate the reaction, followed by extraction, washing, drying, and column chromatography to obtain product 4. Under argon protection, product 4 is dissolved in dichloromethane, then trifluoroacetic acid is added and the reaction is carried out. Toluene is added, and the mixture is distilled under reduced pressure to obtain product 5. Product 5, compound 6, HATU, and DIPEA are dissolved in THF and the reaction is stirred. Water is added to terminate the reaction, followed by extraction, washing, drying, and column chromatography to obtain the protein hydrolysis-targeted chimera for the treatment of multiple myeloma. The protein hydrolysis-targeted chimera for the treatment of multiple myeloma in this invention exhibits significant anti-proliferative activity against RPMI-8266 multiple myeloma cells. The preparation process is simple and suitable for industrial production.

The application is suitable for the technical field of materials, and provides a drug-loaded ligand, a chromium-based metal organic framework material and a preparation method and application thereof, the preparation method of the drug-loaded ligand comprises the following steps: stirring cysteine methyl ester, HATU, 2,5-di(methoxycarbonyl)benzoic acid and diisopropylethylamine in DMF at room temperature for 12 h, and performing washing and purification treatment; the obtained 2-((3-mercapto-1-methoxy-1-oxoprop-2-yl)carbamoyl) terephthalic acid dimethyl ester is added with 3 mL of a sodium hydroxide aqueous solution in THF / MeOH, stirred at room temperature for 18 h, and subjected to acidification and concentrated acid treatment under reduced pressure to obtain the drug-loaded ligand. The application breaks through the traditional physical adsorption or surface modification by adopting the drug-loaded ligand with a cysteine active group to prepare metal organic framework nanoparticles, and simultaneously realizes drug administration by bonding a functional group with radiation protection capability to the ligand through a ligand doping technology.

The invention discloses a preparation method of a dabigatran etexilate precursor, and belongs to the technical field of drug intermediate synthesis. The method comprises the following steps: S1, under the protection of nitrogen, reducing nitro of a compound IV into amino by taking tetrahydroxy diboron and 4, 4 '-dipyridyl as a concerted catalytic system, and purifying to obtain a compound III; s2, pretreating a compound III, a compound II and a condensing agent, performing low-temperature activation and microwave reaction in a DMF / DCM mixed solvent in the presence of HATU, HOAt and DIPEA, and performing post-treatment and recrystallization to obtain an amino amide intermediate; and S3, dissolving the amino amide intermediate in glacial acetic acid, carrying out reflux cyclization, and carrying out post-treatment and recrystallization to obtain a compound I. According to the invention, tetrahydroxy diboron and 4, 4 '-dipyridyl are adopted to synergistically catalyze nitro reduction, the conditions are mild, and the reaction is rapid; by means of synergistic catalysis of HATU and HOAt, water removal through a 4molecular sieve, batch addition of HATU, microwave assistance and the like, the reaction time is shortened, the yield is increased, side reactions are reduced, and the method is suitable for industrial production.

The application relates to a preparation method of Tovorafenib. In the preparation method, HATU is used for amidation, reaction time can be effectively reduced, and yield can be improved; in the application, an amine-free compound is selected as an initial raw material, and the interference of an amine group on the reaction is avoided during amidation, so that the reaction yield is improved; in the preparation method, a cyclic compound is constructed from an initial raw material, and then combined into a target product; the existing commercial compound is selected, the key synthesis step is focused on, the operation method is simple, and the reaction steps are greatly shortened; the post-treatment of the multi-step reaction is simple, and the batch production is suitable.

The present application relates to a kind of drug synthesis process of Tovorafenib.The synthesis process described in the present application, the preparation method of chiral alpha-heteroamine involved, using biological catalyst amine dehydrogenase, directly under mild conditions, one-step reduction amination of latent chiral ketone is into optical pure chiral alpha-heteroamine, it can overcome the deficiency of existing catalytic technology, process route is simple, reaction condition is mild, yield is high, has the advantages, such as step economy, atom economy and other green synthesis, and the advantages, such as good stereoselectivity (ee value is as high as 99%).The condensation method of amino and carboxyl in the synthesis route described in the present application is mostly under HATU and alkaline environment, simple operation, high reaction yield, suitable for batch production.

The invention relates to the technical field of medicine synthesis, in particular to a synthesis method and application of a 2-(3, 4-dimethoxybenzamido) thiazole-4-amide derivative. The structure of the thiazole is as shown in a formula I in the specification. The preparation method of the 2-(3, 4-dimethoxybenzamido) thiazole-4-amide derivative comprises the following step: reacting a compound shown in a formula I with a compound shown in a formula II in the presence of HATU, DIPEA, primary amine or secondary amine and tetrahydrofuran to obtain the 2-(3, 4-dimethoxybenzamido) thiazole-4-amide derivative. The 2-(3, 4-dimethoxybenzoylamino) thiazole-4-amide derivative disclosed by the invention has a relatively good effect of relieving the Alzheimer's disease, and is characterized by having relatively strong cholinesterase inhibitory activity.

The invention belongs to the technical field of heterocyclic compounds, and particularly relates to a proteolysis targeting chimera for treating multiple myeloma as well as a preparation method and application of the proteolysis targeting chimera. Dissolving the compound 2, the compound 3 and HATU in THF, then adding DIPEA, stirring and reacting, adding water to terminate the reaction, extracting, washing, drying, and carrying out column chromatography to obtain a product 4; under the protection of argon, dissolving the product 4 in dichloromethane, and then adding trifluoroacetic acid for reaction; adding methylbenzene, and performing reduced pressure distillation to obtain a product 5; dissolving the product 5, a compound 6, HATU and DIPEA in THF, and stirring for reaction; and adding water to terminate the reaction, extracting, washing, drying, and carrying out column chromatography to obtain the proteolysis targeting chimera for treating multiple myeloma. The proteolysis targeting chimera for treating multiple myeloma has remarkable anti-proliferative activity on multiple myeloma RPMI-8266 cells, the preparation process is simple, and the chimera is suitable for industrial production.

The invention discloses a diagnosis and treatment integrated viscosity response self-assembly nano-micelle as well as a preparation method and application thereof, belongs to the technical field of chemical and biological materials, and aims to solve the problems of curative effect evaluation lagging and invasive detection in existing photo-thermal and photodynamic therapy. The invention provides a preparation scheme of dissolving (E)-3-(5-carboxyl amyl)-2-(2-(5-(4-(diphenylamino) phenyl) thiophene-2-yl) vinyl)-1, 1-dimethyl-1H-benzo [e] indole-3-onium, sulfydryl polyethylene glycol amine, HATU and DIPEA (diisopropylethylamine) in dichloromethane, reacting, self-assembling and purifying, and the obtained nano-micelle has near-infrared fluorescence response and photo-thermal and photodynamic functions. And the curative effect of the drug in treatment of the undifferentiated thyroid cancer can be evaluated in real time by monitoring the viscosity change of a tumor microenvironment.

The application discloses a preparation method of 2-(8-bromimidazo[1,5-a]pyridine-3-yl)propane-2-amine and belongs to the technical field of synthesis of pharmaceutical intermediates. The preparation method of 2-(8-bromimidazo[1,5-a]pyridine-3-yl)propane-2-amine comprises the following steps: step one, condensation of compound I and compound II to obtain compound III; step two, dehydration and ring closure of compound III to obtain compound IV; and step three, hydrazinolysis of compound IV to obtain compound V. The compound V is prepared by adopting a new route, the use of HATU and the Burgess reagent is avoided, product purification is simple, the yield is high, the cost is low, and the method is very suitable for industrial production.

The invention discloses a synthesis method of an aromatic hydrocarbon receptor AHR inhibitor CH223191, and relates to the technical field of synthesis of CH223191. The preparation method comprises the following steps: by taking 1-methylpyrazole-5-formic acid and 4-amino-2, 3-dimethyl azobenzene as initial raw materials, in a DMF (Dimethyl Formamide) solvent, taking HATU (Hydroxyethyl Terephthalate) and DIPEA (Diisopropylethylamine) as amidation condensation reagents, and reacting at normal temperature to prepare CH223191; and after the reaction is completed, separating by adopting a liquid-liquid extraction method (ethyl acetate / deionized water), and further purifying by adopting a silica gel column chromatography to obtain the high-purity target compound CH223191. The synthetic route is short, the operation is simple, convenient and rapid, the separation and treatment of unstable diazonium salt are avoided, and the operation safety and the reaction efficiency are remarkably improved; the obtained product is high in purity, the yield reaches 90% or above, and an important basis is provided for researching a biotoxic mechanism related to AHR excessive activation and preventing and treating diseases.

The application belongs to the technical field of organic synthesis, and specifically provides a 2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,1,3,3-tetramethylurea hexafluorophosphate, a preparation method and a condensation reagent. The preparation method of the 2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,1,3,3-tetramethylurea hexafluorophosphate comprises: making 2-chloro-4,6-dimethoxy-1,3,5-triazine and tetramethylurea undergo a nucleophilic substitution reaction to generate an intermediate; and making the intermediate and potassium hexafluorophosphate undergo an ion exchange reaction to generate the 2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,1,3,3-tetramethylurea hexafluorophosphate. The 2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,1,3,3-tetramethylurea hexafluorophosphate according to the embodiment of the application can be used as a condensation reagent for forming an amide bond, and compared with condensation reagents such as HBTU and HATU which have two high-energy heteroatomic bonds of N-N and N-O, the thermal hazard of the 2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,1,3,3-tetramethylurea hexafluorophosphate is smaller, and the 2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,1,3,3-tetramethylurea hexafluorophosphate is suitable for industrial production. In addition, the preparation method according to the embodiment of the application has mild reaction, fewer reaction steps and low operation risk coefficient.

The invention belongs to the technical field of organic synthesis, and particularly provides 2-(4, 6-dimethoxy-1, 3, 5-triazine-2-yl)-1, 1, 3, 3-tetramethylurea hexafluorophosphate, a preparation method and a condensation reagent. The preparation method of the 2-(4, 6-dimethoxy-1, 3, 5-triazine-2-yl)-1, 1, 3, 3-tetramethylurea hexafluorophosphate comprises the following steps: carrying out nucleophilic substitution reaction on 2-chloro-4, 6-dimethoxy-1, 3, 5-triazine and tetramethylurea to generate an intermediate; and carrying out ion exchange reaction on the intermediate and potassium hexafluorophosphate to generate 2-(4, 6-dimethoxy-1, 3, 5-triazine-2-yl)-1, 1, 3, 3-tetramethylurea hexafluorophosphate. The 2-(4, 6-dimethoxy-1, 3, 5-triazine-2-yl)-1, 1, 3, 3-tetramethylurea hexafluorophosphate provided by the embodiment of the invention can be used as a condensation reagent for forming an amido bond, and compared with condensation reagents with two high-energy heteroatom bonds of N-N and N-O, such as HBTU and HATU, the 2-(4, 6-dimethoxy-1, 3, 5-triazine-2-yl)-1, 1, 3, 3-tetramethylurea hexafluorophosphate is smaller in heat hazard and suitable for industrial production. In addition, according to the preparation method of the embodiment of the invention, the reaction is mild, the reaction steps are few, and the operation danger coefficient is low.

The invention relates to the technical field of biomass mass spectrometry detection, and particularly discloses a mass spectrometry detection method for metabolites containing carboxyl and / or carbonyl based on a boric acid material, which comprises the following steps: step 1, mixing a to-be-detected substance with an HATU solution; step 2, injecting the mixed solution into a boric acid coating capillary tube loaded with an AEAP-diol functional probe; step 3, repeatedly shaking the capillary tube to enable the mixed solution and the AEAP-diol functionalized probe to fully interact, and carrying out derivatization reaction; step 4, washing the capillary tube to remove HATU and impurities; step 5, cracking the borate bond in the capillary tube and releasing the AEAP-diol functionalized probe labeled molecules of the object to be detected; and step 6, carrying out mass spectrometry detection by adopting a mass spectrometer. According to the invention, efficient, sensitive and accurate on-line mass spectrometry detection and analysis of the carboxyl and / or carbonyl-containing metabolite are realized, and the technical problems of poor ionization efficiency, insufficient detection sensitivity and serious matrix interference in direct mass spectrometry detection and analysis of the carboxyl and / or carbonyl-containing metabolite are effectively solved.

This invention belongs to the field of compound preparation technology, and provides a 4-aryloxyphenyl-1,4-dihydroquinoline-3-carboxamide compound, its preparation method, and its application. The method of this invention includes the following steps: reacting compound 1, potassium carbonate, and a phenol compound; mixing compound 2, methanol, water, and lithium hydroxide to obtain compound 3; acylating compound 3, thionyl chloride, and sodium bromide, followed by reaction with tin chloride dihydrate and ethanol to obtain compound 4; reacting compound 5 with DMF-DMA; reacting compound 6, substituted aniline, and cesium carbonate followed by hydrolysis to obtain compound 8; and reacting compound 4, compound 8, HATU, and DIPEA. The compounds of this invention are used to prepare anti-inflammatory drugs, treating inflammation and inflammation-related diseases by inhibiting the release of inflammatory factors (TNF-α and / or IL-6) from macrophages.

The invention belongs to the technical field of polysaccharide preparation, and particularly relates to aminated lentinan as well as a preparation method and application thereof. The method comprises the following steps: dissolving lentinan in an organic solvent, then adding succinic anhydride, and carrying out a first reaction to obtain LNT-COOH after the reaction is finished; the preparation method comprises the following steps: dissolving lentinan in an organic solvent, sequentially adding HATU, HOBT and DIEA, stirring, reacting, adding H2N-NHBOC after the reaction is finished, carrying out an amination reaction, adding trifluoroacetic acid after the amination reaction is finished, and stirring to obtain aminated lentinan. The method disclosed by the invention has the characteristics of simplicity and convenience in operation and high reaction efficiency, and the obtained aminated lentinan has better solubility, biocompatibility and remarkable biological activity, and is suitable for development and application of medicines, health-care products and other biological materials.