66 results about "Intramolecular cyclization" patented technology

Disclosed herein are methods of synthesizing compounds of the formula (I) wherein the variables are defined herein. Also provided are compounds produced using these methods. In some aspects, the methods provided herein may be used to install aryl bioisosteres.

The invention discloses a preparation method of an arfamarana key intermediate, which comprises the following steps: carrying out nucleophilic addition reaction on a compound I and 1-[3-chloro-5-(trifluoromethyl) phenyl]-2, 2, 2-trifluoroethanone under the action of an organic solvent A and alkali to obtain a compound II; dissolving the compound II in an organic solvent B, adding concentrated sulfuric acid, carrying out intramolecular dehydration and cyanogen hydrolysis, and after the reaction is finished, cooling to room temperature for crystal growing to obtain a compound III; dissolving the compound III in an organic solvent C, carrying out intramolecular cyclization and ester hydrolysis reaction on the compound III and hydroxylamine hydrochloride under the action of a certain amount of sodium hydroxide aqueous solution, and after the reaction is finished, collecting a water phase and adjusting the pH value of the water phase, so as to obtain the key intermediate of arfampanaga. The reaction in each step has a high conversion rate, the purity of the prepared arfamarin intermediate is high, and powerful support and guarantee are provided for preparation of high-purity arfamarin.

The invention discloses a method for rapidly and efficiently preparing a series of novel ester group facaplysin derivatives by combining EDCI and HOBT to react with carboxyl facaplysin and directly carrying out ester exchange reaction on an active ester intermediate and alcohol without separation. The invention also discloses application of the derivatives in resisting methicillin-resistant staphylococcus aureus and escherichia coli. The preparation method comprises the following steps that EDCI and HOBT are combined to activate carboxyl facaplysin for reaction, an activated ester intermediate is generated, the activated ester intermediate and alcohol are directly subjected to esterification reaction without separation, and a series of ester-based facaplysin derivatives are obtained. According to the preparation method, ester-based Fascaplysin derivatives with different structures can be rapidly and efficiently constructed, and compared with a traditional method that ester-based carboline derivatives are firstly synthesized and then high-temperature intramolecular cyclization is performed, the time and the raw material cost are greatly saved, the synthesis efficiency is improved, the reaction process is observable and controllable, and the yield is stable. And the synthesized ester group facaplysin derivative has excellent antibacterial activity on methicillin-resistant staphylococcus aureus and escherichia coli.

The invention relates to the technical field of cyclic polypeptides, in particular to a cyclic pentapeptide containing an Fmoc protecting group and a preparation method of the cyclic pentapeptide. The preparation method comprises the following steps: carrying out coupling reaction on dipeptide containing Fmoc-Cbz-lysine and tripeptide containing OBn-OtBu-glutamic acid to form straight-chain pentapeptide containing Fmoc, Cbz, OBn and OtBu; removing Cbz and OBn to form a straight-chain pentapeptide containing Fmoc and OtBu; carrying out intramolecular cyclization reaction to form cyclic pentapeptide containing Fmoc and OtBu; and removing OtBu to form the cyclic pentapeptide containing the Fmoc protecting group. The preparation method is high in cyclization yield, can adapt to various amino acid sequences, can synthesize the cyclic polypeptide containing the side chain protecting group, does not need a solid-phase carrier in the cyclization step, and can remarkably reduce the production cost.

The invention belongs to the technical field of fluorescent probes, and particularly relates to a single-molecule fluorescent probe based on a phenothiazine structure as well as a preparation method and application of the single-molecule fluorescent probe. The preparation method comprises the following steps: firstly introducing an alkyl chain to a nitrogen atom of a raw material to obtain the phenothiazine structure-based single-molecule fluorescent probe, then carrying out regioselective formylation on the raw material to obtain the phenothiazine structure-based single-molecule fluorescent probe, then treating the raw material by adopting aluminum trichloride to realize O-demethylation, and finally carrying out intramolecular cyclization reaction on the raw material and 1H-benzimidazole-2-acetonitrile to obtain the phenothiazine structure-based single-molecule fluorescent probe. The single-molecule fluorescent probe based on the phenothiazine structure prepared by the invention is compatible with orthogonal chemical reaction activity and maintains controllable electron transfer, so that different chemical events are converted into specific optical signals, and selective and mechanism specific fluorescent response to phosgene, copper ions and hypochlorite is realized.

The invention belongs to the technical field of resource recovery of scrapped chemical defense hazardous articles, and particularly relates to a resource recovery disposal method for scrapped Sieve explosion type tear bombs. Specifically, the invention provides a green process for directionally converting CS in a scrapped projectile body into a high-added-value medical intermediate 2-(2-chlorphenyl) benzimidazole. According to the process, pulverization pretreatment of a main charge grain is achieved through swelling treatment, wet crushing and drying, and CS is efficiently recycled through multi-step dissolution and extraction; cS and o-phenylenediamine are taken as raw materials, six-step continuous reaction of nucleophilic addition, acid-base neutralization, nucleophilic substitution, proton migration / elimination, intramolecular cyclization and oxidative aromatization is carried out, and the CS and o-phenylenediamine are directionally converted into 2-(2-chlorphenyl) benzimidazole. According to the disposal method, high-risk waste is converted into medical intermediates, waste resource utilization is achieved, pollution and safety risks caused by a traditional incineration / blasting method are avoided, and the problem of disposal of current decommissioning tear bombs is solved.

The invention discloses a synthesis method of a cyclic oligomer carbazole phosphate hole transport material. According to the material, carbazole phosphoric acid units are directionally connected into a cyclic oligomeric structure through intramolecular cyclization design, cyclic oligomer carbazole phosphoric acid with different hydrolysis degrees is obtained by adjusting the concentration of trimethylbromosilane in hydrolysis reaction, and the charge transfer capacity and the interface passivation effect of the material are remarkably improved. Compared with the traditional self-assembled monomolecular layer (SAM) type carbazole phosphoric acid micromolecule (such as PACz), the Cyclic-PACz has better long-term operation stability and large-area coating compatibility.

The present invention provides industrially suitable processes for preparing intermediates in the production of substituted polycyclic pyridone derivatives having a cap-dependent endonuclease inhibitory activity. In the process as shown below, wherein each symbol is as defined in the specification, an optically active substituted tricyclic pyridone derivative of the formula (VII) is obtained in high yield and high enantioselectivity by subjecting a compound of the formula (III) or (VI) to intramolecular cyclization with controlling stereochemistry to obtain a compound of the formula (IV) having a removable functional group on an asymmetric carbon, and then removing the functional group thereof;

This invention discloses a method for synthesizing a tenapano hydrochloride intermediate. The synthesis method includes the following steps: (1) condensing the compound 3-bromophenylacetaldehyde and the compound N-methyl-(2,4-dichlorophenyl)methylamine under dehydration conditions to obtain an enamine intermediate; (2) subjecting the enamine intermediate to an intramolecular cyclization reaction in the presence of an acid catalyst to obtain the tenapano hydrochloride intermediate 4-(3-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline. The synthetic route provided by this invention requires only two steps to construct the key framework, and has the advantages of short reaction steps, high overall yield, and no need to use highly toxic liquid bromine. This process has high atom economy, reduces the emission of waste gas, wastewater, and solid waste, and is suitable for large-scale industrial production under mild conditions.

The invention relates to a method for preparing 2-aryl-3-difluoromethyl benzothiophene by utilizing an electrochemical reaction. Specifically, the invention provides an electrochemical anodic oxidation cathode reduction characteristic instead of a traditional chemical oxidation reducing agent, sodium difluoromethanesulfinate is used as a difluoromethyl donor, and a difluoromethyl free radical is excited through electrochemical anodic oxidation, so that the difluoromethyl free radical is synthesized. The preparation of the target molecule 2-aryl-3-difluoromethyl benzothiophene is realized through intramolecular cyclization initiated by addition of free radicals to active alkyne. The method does not need to add an additional transition metal catalyst and a super-stoichiometric redox agent, has the advantages of mild reaction conditions, high product yield, good chemical selectivity and the like, better conforms to the purpose of green and sustainable development of the current society, and has a good industrial application prospect.

The invention provides a synthesis method of celacarburine and a key intermediate thereof, which comprises the following steps: taking methyl 4-aminobutyrate hydrochloride as an initial raw material, and sequentially carrying out o-nitrobenzenesulfonyl protection, alkylation, amide condensation, hydrolysis and deprotection, intramolecular cyclization, removal of o-nitrobenzenesulfonyl protecting group and optional acylation reaction to obtain a target product. A synthetic route is designed through an innovative strategy, the technical bottlenecks that raw materials and reagents are difficult to obtain, steps are tedious, conditions are harsh, the yield is low and the like which commonly exist in an existing macrocyclic synthesis method are overcome, and the target product is simply and safely prepared in a high-yield mode under the mild condition. The method has the advantages of cheap and easily available raw materials and reagents, simple operation, mild conditions and no need of special equipment, has significant industrial application potential, and provides a stable and reliable material basis for subsequent pharmacological research and new drug development of celacarflurine.

The application provides a synthesis method of celacarfurine and key intermediates thereof, comprising the following steps: taking 4-amino butyric acid methyl ester hydrochloride as a starting material, sequentially performing ortho-nitrobenzenesulfonyl protection, alkylation, amide condensation, hydrolysis and deprotection, intramolecular cyclization, deprotection of ortho-nitrobenzenesulfonyl, and optional acylation to obtain a target product. The synthesis route is designed by an innovative strategy, and overcomes technical bottlenecks such as difficulty in obtaining raw materials and reagents, long steps, harsh conditions and low yield which exist in the existing macrocycle synthesis method, and the target product is prepared under mild conditions with high yield, simplicity and safety. The method is simple in operation, mild in conditions, and does not need special equipment, has significant industrial application potential, and provides a stable and reliable material basis for subsequent pharmacological research and new drug development of celacarfurine.

The present invention relates to a novel synthetic procedure utilizing domino Knoevenagel- cyclization reactions, in which the furan, thiophene or pyrrole subunits of the substrates undergo a Diels-Alder cycloaddition as either a diene or a dienophile producing novel condensed tetra- penta- or hexacycles with bridged or spirocyclic dihydrofuran, -thiophene or -pyrrole moiety. The five-membered aromatic heterocyclic subunit reacts intramolecularly as a diene with the double bond in a [4+2] or [4+4] cycloaddition (1,4-addition to five-membered heterocycle) producing bridged scaffolds. The cyclization step can also be an intramolecular hetero Diels- Alder reaction, in which a heterodiene reacts intramolecularly with the π-excessive five- membered heterocycles acting as a dienophile in the 1,2-addition. Some of the novel condensed heterocyclic products have antiproliferative activity and thus both the compounds and their therapeutic application are subject of the invention.

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

The invention relates to a preparation method of 4-oxa-7-azaspiro [2.5] octane-6-ketone, and belongs to the field of chemical synthesis of medicines. Hydrochloride of glycine ester is used as a starting material, and 4-oxa-7-azaspiro [2.5] octane-6-ketone is obtained through five steps of protecting group introduction, cyclization, condensation, protecting group removal and intramolecular cyclization reaction and serves as the starting material of the anti-influenza virus medicine and analogues of the anti-influenza virus medicine. The synthesis route is ingenious in design, the use of a palladium catalyst and a harmful reagent chloroacetyl chloride in the prior art is reduced or avoided, and the material cost and the production cost of the whole route are reduced by 70% or above compared with those of the prior art by improving the yield of the two key reactions of condensation and cyclization and simplifying the operation steps. The method is suitable for industrial application.

The invention discloses a metallocene complex and a preparation method thereof.The preparation method comprises the steps that a 2, 5-pentanedione derivative which is cheap and commercially available serves as a starting raw material, a cyclopentenone derivative is generated through alkali catalytic intramolecular cyclization, then the cyclopentenone derivative reacts with a Grignard reagent to generate a cyclopentadiene derivative, and the metallocene complex is obtained. And finally, protons are captured through sodium hydride and then react with zirconium chloride to obtain the metallocene complex, compared with some routes with complex initial raw materials or routes related to medicine control, reagents involved in the reaction process are commercially available cheap raw materials, the reaction conditions are mild, the method is suitable for industrial production, and the method further has the amplified production potential.

The invention belongs to the field of organic chemical synthesis, and relates to a method for synthesizing a natural product Pyrroloazocine indole alkaloid skeleton. According to the method, a commercially available compound 1 and phenylhydrazine are taken as synthesis starting points, and a [2.2. 2] bridge ring system is constructed through key Fischer indole synthesis, Stille coupling reaction and intermolecular Diels-Alder reaction. The preparation method comprises the following steps: carrying out a cyclopropanation reaction mediated by carbene, carrying out a Ley-Griffith oxidation reaction, and carrying out a Beckmann rearrangement and an intramolecular SN2 cyclization cascade reaction so as to realize the construction of the core skeleton of the Pyrroloazocine indole alkaloid. According to the method, a material basis can be provided for activity testing of the Pyrroloazocine indole alkaloid and the analogue thereof, and a thought is provided for synthesis route design of more complex cage-shaped indole alkaloid basic frameworks.

This invention discloses a method for synthesizing 3-oxa[3.1.1]spiropropane, belonging to the fields of organic synthetic chemistry and medicinal chemistry. This method is the first to introduce oxygen atoms into the high-strength skeleton of [3.1.1]spiropropane, successfully synthesizing the 3-oxa[3.1.1]spiropropane molecule. The specific synthetic route is as follows: starting with 3,3-bis(bromomethyl)oxacyclobutane, the 3-oxabicyclo[3.1.1]heptane diol skeleton is constructed sequentially via nucleophilic substitution with diethyl malonate, reduction, and intramolecular cyclization. Then, oxidation and Barton decarboxylation iodination are performed to obtain the key intermediate 1,3-diiodo-3-oxabicyclo[3.1.1]heptane, which is finally reacted with an organolithium reagent to obtain the target product. This invention fills a technological gap in the synthesis of heteroatom-substituted spiroalkyl, providing a key precursor for the subsequent development of its free radical bifunctionalization reaction and the construction of structurally diverse 3-oxabicyclic [3.1.1]heptane dominant skeletons. It has important application prospects in drug design, especially as a bio-electroisoster of meta-substituted aromatics.

The application discloses a method for selectively preparing quinolin-2-ketone or 3,4-dihydroquinolin-2-ketone compounds by regulating a photocatalyst, and the method is characterized in that quinolin-2-ketone or 3,4-dihydroquinolin-2-ketone compounds are prepared by intramolecular cyclization of 1,7-alkenyl alkynes under a photocatalytic condition; the selectivity of the product is controlled by the photocatalyst; when a Cu(I) photocatalyst with strong reducing capacity is used, 3,4-dihydroquinolin-2-ketone compounds are obtained; when a Cu(I) photocatalyst with weak reducing capacity is used, quinolin-2-ketone compounds are obtained; the raw material is simple and easy to obtain, the reaction condition is mild, the substrate has good universality, and the method is suitable for industrial production.

The application discloses a synthesis method of an oxazoline compound. The method is as follows: taking an olefin compound which is cheap and easy to obtain as a starting material, performing amine functionalization on the olefin in the presence of a catalyst, an amination reagent, a base and an additive, and then performing intramolecular cyclization to obtain the oxazoline compound in one step with high selectivity. The method has the characteristics of high atom economy, wide source of raw materials, avoidance of use of anhydrous and oxygen-free operation conditions, simple process and the like, and is suitable for large-scale production.

The invention relates to a semiconductor hole fluorescent probe and application thereof, and belongs to the technical field of fluorescent probes. The semiconductor hole fluorescent probe has a diarylmethane skeleton structure, and can be efficiently oxidized by holes by utilizing the high electron cloud density of carbon atoms in the center of the diarylmethane skeleton, so that intramolecular cyclization reaction is carried out, a fluorescent dye with a rigid plane structure is generated, and fluorescent lightening is realized; the carbon positive ion active site in the center of the oxidation product can be rapidly and irreversibly quenched by water molecules in the environment to realize signal reset, so that the semiconductor hole specificity response can be realized, and the single particle level lossless imaging of hole behaviors in P-type, N-type and PN junctions can be realized.

The invention belongs to the technical field of biochemistry, and particularly relates to a method for synthesizing a flavanone compound through nano-enzyme catalyzed carbene transfer and intramolecular ring closing. The monatomic nano-enzyme is applied to catalysis of non-natural reaction, and the monatomic nano-enzyme is found to have the capability of mediating carbene transfer. 24 flavanone compounds are successfully synthesized by catalyzing a substrate diazo compound through the screened nano-enzyme and organic solvent, and the yield for a plurality of substrates of the type is high. The method disclosed by the invention is simple to operate, mild in condition, low in catalyst cost, high in stability and long in service life, a nano-enzyme catalysis method is good in substrate universality, a mild and direct method is provided for synthesizing the flavanone compound, and the method has a very good industrial application prospect.

The present application relates to the field of photocatalytic organic synthesis, and particularly to a visible light induced tandem radical addition-cyclization reaction for constructing an aromatic heterocycle linked indole ketone compound and a preparation method thereof.By introducing an unsaturated group at the ortho position of a ketoxime ester, a new intramolecular cyclization pathway is generated to realize the construction of a new aromatic heterocycle radical, and a preparation method of the aromatic heterocycle linked indole ketone compound is further provided, and the specific molecular structure is shown in the following formula (I). The present application has the advantages of easy availability of raw materials, simple operation, mild conditions, simple synthesis route, high synthesis efficiency, strong functional group adaptability of the substrate, potential application value in the biological and medical fields due to the particularity and designability of the aromatic heterocycle linked indole ketone structure.

The invention belongs to the technical field of organic synthesis and high polymer materials, and particularly discloses a novel method for preparing monosubstituted glycolide and a polymer thereof. According to the method, a lactate derivative and glycollic acid are taken as initial raw materials, a series of mono-substituted glycolide is synthesized with high selectivity through acid catalysis ester exchange and intramolecular cyclization dehydration, and then the mono-substituted glycolide polymer with a specific structure is prepared through ring-opening polymerization. The core of the method is as follows: excessive glycollic acid is used for inhibiting ester exchange side reaction of lactate and promoting ester exchange reaction between glycollic acid and lactate to obtain a key intermediate, and finally, the monosubstituted glycolide monomer is obtained through one-step condensation cyclization by using the chemical structure stability of monosubstituted glycolide. The monomers can be prepared into corresponding degradable polyester through ring opening polymerization. The invention provides a general synthesis path for preparing cyclic lactone and functional polyester materials with regular structures and adjustable side chains on a large scale from bulk raw materials.

The invention relates to a diazotization ring closing method for synthesizing a 4, 4-dimethyl-4H-cyclopentane benzophenanthrene compound. The diazotization ring closing method comprises the following steps of: adding a diazotization reagent; according to the method, an amino-containing biphenyl dimethyl fluorene compound is taken as a raw material, diazotization reaction and intramolecular ring-closing reaction are continuously completed in the same reaction system under anhydrous and anaerobic conditions, and the benzophenanthrene fused ring skeleton is directly constructed. According to the method, a diazo intermediate is generated in situ under an acidic condition, and is promoted to be converted to an intramolecular cyclization direction in the presence of a copper salt catalyst and a drying agent, so that the problems that a dibenzfluorene system is large in tension, and a traditional aminophenanthrene ring method is low in conversion rate and has many side reactions are effectively solved. The method is mild in reaction condition, independent of a high-load noble metal catalyst, simple and convenient to operate, good in adaptability to substituent groups, suitable for large-scale implementation and good in industrial application prospect.

The application relates to a rapamycin-G4H nanocapsule, a preparation method and application thereof. The preparation method of the rapamycin-G4H nanocapsule comprises the following steps: S1. preparing a rapamycin micelle by adopting a film hydration method; S2. modifying a dibenzocyclooctyne amplification primer on the surface of the rapamycin micelle through a click chemistry reaction to obtain a rapamycin micelle modified with the amplification primer; S3. taking a linear DNA molecule as a template, and synthesizing a circular amplification template through an intramolecular cyclization reaction; and S4. incubating the circular amplification template, the rapamycin micelle modified with the amplification primer, a thermophilic DNA polymerase, a pyrophosphatase, dNTP and Co-G4-haem DNAzyme under the condition of a thermophilic DNA polymerase reaction buffer. The rapamycin-G4H nanocapsule can play an efficient antioxidant stress and immune inflammatory regulation function, can improve the intraocular microenvironment of a glaucoma patient, and can inhibit the continuous apoptosis of retinal ganglion cells.

The application provides a synthesis method and antitumor application of several furanopyrimidine-ibuprofen hybrid derivatives, which are linked by aza-wittig reaction, intramolecular cyclization, substitution reaction, hydrolysis and acidification reaction and the like, and a fused triazole, a hydrazide, a bis-hydrazide and an oxadiazole are used as a bond bridge key, so that different series of furanopyrimidine-ibuprofen hybrid derivatives are synthesized in a simple and efficient manner. The CCK8 method in vitro pharmacodynamics test proves that the target compound has proliferation inhibition activity on A549 lung cancer cells and HepG2 liver cancer cell lines. Test results show that the target compound shows good proliferation inhibition activity on the two kinds of cells, and the structural formula is as follows:

The application discloses a preparation method of pyrazoline, which comprises the following steps: (1) mixing a ketone hydrazine raw material with a Lewis acid catalyst, and heating to perform a reaction to obtain a reaction mixture; and (2) cooling and filtering the reaction mixture, and purifying to obtain a pyrazoline product. In the application, the Lewis acid catalyst acts as an electron pair acceptor, coordinates with a nitrogen atom or an oxygen atom in the ketone hydrazine, and activates the ketone hydrazine molecule; the activated ketone hydrazine molecule is more prone to intramolecular cyclization reaction, and forms a pyrazoline ring; the Lewis acid does not provide a proton, and thus the hydrolysis of the ketone hydrazine and side reactions caused by a protonic acid catalyst are avoided, and the selectivity and yield of the product are improved; in addition, the Lewis acid catalyst can be filtered and recycled for reuse, meets the principle of green chemistry, and reduces environmental pollution and resource waste; and the preparation method has low requirements on reaction conditions, is simple to operate, and is suitable for industrial production.

Catalytic processes to produce on purpose piperazine are described. The processes are based on the use of a 10-member ring zeolite, preferably with MFI topology, with tunned morphology and acidity to promote intermolecular or intramolecular cyclization of alkanolamines, ethyleneamines, or diols to cyclic piperazine. The unavoidable byproducts due to thermodynamics can be tuned to favor piperazine upon recycling. The processes can be used to manufacture piperazine which can be used as solvent for post-combustion CO2 capture.

The application provides a pyrazine compound and a preparation method and application thereof, a nitryl pyrazine compound and a preparation method and application thereof, and a preparation method of an upatin intermediate, and relates to the technical field of drug synthesis. The pyrazine compound with the structure shown in formula IV is subjected to an addition reaction with nitromethane to obtain a nitryl pyrazine compound with the structure shown in formula III, and then, under the condition of an alkaline reagent, an intramolecular cyclization-aromatization reaction is performed to obtain an upatin intermediate with the structure shown in formula II. Compared with the prior art, the application does not need to use expensive metal catalysts (such as a palladium catalyst) and other expensive silicon reagents, but only needs to use inexpensive and easily available formaldehyde aqueous solution and nitromethane, so that the production cost of the upatin intermediate is greatly reduced; and compared with the use of acetaldehyde gas, the application uses formaldehyde aqueous solution, and the operation is more simple, and the application is more conducive to industrialized production.