- Pyridinium-N-(2-pyridyl)aminides: A selective approach to substituted 2-aminopyridines
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Differently substituted 2-aminopyridines have been prepared in two steps from pyridinium-N-(2-pyridyl)aminide.
- Carceller, Rosa,Garcia-Navio, Jose L.,Izquierdo, Maria L.,Alvarez-Builla, Julio
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- Tertiary formylated amines by microwave irradiation of N,N-dimethyl- N′-(2-pyridyl) formamidines with methyl vinyl ketone
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Treatment of N,N-dimethyl-N′-(2-pyridyl)formamidine with methyl vinyl ketone under microwave irradiation yields N-formyl-N-(3-oxobutyl)-2- pyridylamine without decomposition or polymerization of methyl vinyl ketone. The result is an alternative non-oxidat
- Gomez-Garcia, Omar,Salgado-Zamora, Hector,Campos-Aldrete, Elena
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- Preparation of 2,3-Disubstituted 5-Bromo-1 H -pyrrolo[2,3- b ]pyridine Framework by Fischer Cyclization
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A simple synthesis of some hard-to-reach heterocycles containing 2,3-disubstituted 5-bromo-1H-pyrrolo[2,3-b]pyridine framework by FisNher indole cyclization in polyphosphoric acid has been developed. A particularly valuable feature of this synthetic route is the possibility to build a 5-bromo-7-azaindole scaffold with alkyl or aryl substituents at positions 2 and 3 from available starting materials.
- Alekseyev, Roman S.,Amirova, Sabina R.,Terenin, Vladimir I.
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- Metal-Free Reduction of Aromatic Nitro Compounds to Aromatic Amines with B2pin2 in Isopropanol
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A metal-free reduction of aromatic nitro compounds to the corresponding amines has been achieved by a combination of B2pin2 and KOtBu in isopropanol. A series of nitro compounds containing various reducible functional groups were chemoselectively reduced in good to excellent yields.
- Lu, Hongtao,Geng, Zhiyue,Li, Jingya,Zou, Dapeng,Wu, Yusheng,Wu, Yangjie
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- Nitrogen-doped graphene-activated iron-oxide-based nanocatalysts for selective transfer hydrogenation of nitroarenes
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Nanoscaled iron oxides on carbon were modified with nitrogen-doped graphene (NGr) and found to be excellent catalysts for the chemoselective transfer hydrogenation of nitroarenes to anilines. Under standard reaction conditions, a variety of functionalized and structurally diverse anilines, which serve as key building blocks and central intermediates for fine and bulk chemicals, were synthesized in good to excellent yields.
- Jagadeesh, Rajenahally V.,Natte, Kishore,Junge, Henrik,Beller, Matthias
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- The acid-catalysed synthesis of 7-azaindoles from 3-alkynyl-2- aminopyridines and their antimicrobial activity
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The synthesis of 7-azaindoles from 3-alkynyl-2-aminopyridines using acidic conditions, namely, a mixture of trifluoroacetic acid (TFA) and trifluoroacetic anhydride (TFAA), is described. This methodology resulted in the synthesis of fifteen 7-azaindoles, with most containing substituents at the 2- and 5-positions. The majority of these were tested for antimicrobial activity against a range of bacteria and yeasts. The 7-azaindoles displayed the best activity against the yeasts, particularly against Cryptococcus neoformans, where activities as low as 3.9 μg ml-1 were observed.
- Leboho, Tlabo C.,Van Vuuren, Sandy F.,Michael, Joseph P.,De Koning, Charles B.
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- Handling Hydrogen Peroxide Oxidations on a Large Scale: Synthesis of 5-Bromo-2-nitropyridine
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5-Bromo-2-nitropyridine was prepared from the corresponding amine via hydrogen peroxide oxidation in large scale production. This transformation initially showed low conversion, high impurity content and lack of reproducibility in lab trials. Parallel to process development, safety studies were conducted to investigate the stability of oxidant mixture, its composition and the oxidation reaction itself by reaction and adiabatic calorimetry. The resulting robust reaction conditions and appropriate safety boundaries allowed to develop a reproducible, safe protocol for the implementation of this chemistry on large scale, obtaining consistent results throughout the campaign.
- Agosti, Alessandro,Bertolini, Giorgio,Bruno, Giacomo,Lautz, Christian,Glarner, Thomas,Deichtmann, Walter
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- Directing Group Enables Electrochemical Selectively Meta-Bromination of Pyridines under Mild Conditions
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Without the use of catalysts and oxidants, a facile and sustainable electrochemical bromination protocol was developed. By introducing the directing groups, the regioselectivity of pyridine derivatives could be controlled at themeta-position utilizing the inexpensive and safe bromine salts at room temperature. A variety of brominated pyridine derivatives were obtained in 28-95% yields, and the reaction could be readily performed at a gram scale. By combining the installation and removing the directing group, the concept ofmeta-bromination of pyridines could be verified.
- Wu, Yanwei,Xu, Shanghui,Wang, Hong,Shao, Dongxu,Qi, Qiqi,Lu, Yi,Ma, Li,Zhou, Jianhua,Hu, Wei,Gao, Wei,Chen, Jianbin
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- Halogenation of pyridinium-N-(2'-pyridyl)aminide: An easy synthesis of halo-2-aminopyridines
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The regioselective halogenation of pyridinium-N-(2'-pyridyl)aminide 1 with N-chloro, bromo or iodosuccinimide under mild conditions is described. The method, combined with a reduction of the N-N bond, allows an easy preparation of 5-halo and 3,5-dihalo-2-aminopyridines 4.
- Burgos,Delgado,Garcia-Navio,Izquierdo,Alvarez-Builla
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- Synthesis of a fluorine-18 labeled derivative of epibatidine for in vivo nicotinic acetylcholine receptor PET imaging
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Epibatidine (exo-2-(2'-chloro-5'-pyridyl)-7-azabicyclo[2.2.1]heptane), a natural compound isolated from the skin of the Ecuadorian poison frog Epipedobates tricolor, is the most potent nicotinic acetylcholine receptor (nAChR) agonist reported to date. In order to visualize and quantify in vivo these receptors in human brain using Positron Emission Tomography (PET), [18F]norchlorofluoroepibatidine (exo-2-(2'-[18F]fluoro-5'-pyridyl)-7-azabicyclo[2.2.1]heptane), a fluorine-18 (t(1/2): 110min) radiolabeled derivative of epibatidine has been designed. The corresponding 2'-bromo-, 2'-iodo- and 2'-nitro exo-2-(5'-pyridyl)-7-azabicyclo[2.2.1]heptane analogues as labeling precursors, as well as norchlorofluoroepibatidine as a reference compound have been synthesized by reductive, stereoselective, palladium-catalyzed Heck-type coupling between an N-Boc protected azanorbornene and the corresponding halopyridine. [18F]Norchlorofluoroepibatidine has been radiolabeled with fluorine-18 by nucleophilic aromatic substitution from the corresponding Boc-protected halo- and nitro precursors using [18F]FK-K222 complex in DMSO by conventional heating (at 150-180°C for 10min) or microwave activations (at 100 Watt, for 1 to 2.5min), followed by TFA-removal of the protective group. Typically, using the microwave activation procedure, 60-80mCi (2.22-2.96 GBq) of pure [18F]norchlorofluoroepibatidine could be obtained in less than 2h (110-115min) from the bromo labeling precursor, with specific radioactivities of 1.5-2.5Ci/μmol (55.5-92.5GBq/μmol) calculated for End of Bombardment. The preliminary PET experiments in baboon (Papio papio) with [18F]norchlorofluoroepibatidine show a high uptake and a rapid accumulation of the radiotracer into the brain within 30min. In the thalamus, a nAChR rich area, uptake of radioactivity reached a maximum at 40min (10% I.D./100mL tissue). The ratio of radioactivity thalamus/cerebellum (the latter being a nAChR poor area) was 2 at 40min and increased with time, up to 4.3 at 160min. Its specific regiodistribution and its high ratio of specific-to-nonspecific binding confirm the ideal profile of [18F]norchlorofluoroepibatidine as a suitable radioligand for PET imaging of nAChRs in the brain. Copyright (C) 1999 Elsevier Science Ltd.
- Dolci, Lilian,Dolle, Frederic,Valette, Heric,Vaufrey, Francoise,Fuseau, Chantal,Bottlaender, Michel,Crouzel, Christian
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- Mild regioselective halogenation of activated pyridines with N-bromosuccinimide
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Regioselective mono and dihalogenations of amino, hydroxy and methoxy pyridines (2-, 3-, and 4-substituted) as well as 2,6-dimethoxy pyridine with N-bromosuccinimide in different solvents have been studied. Reactivity of the substrates decreases in the order amino>hydroxy>methoxy and regioselectivity depends on the position of the substituent (2-substituted > 3-substituted). In most of the cases we obtained monobrominated derivatives regioselectively and in high yields. Hydroxy and amino pyridines can also be dibrominated in almost quantitative yield with 2 equivalents of NBS.
- Canibano,Rodriguez,Santos,Sanz-Tejedor,Carreno,Gonzalez,Garcia-Ruano
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- Electrochemical C-H Halogenations of Enaminones and Electron-Rich Arenes with Sodium Halide (NaX) as Halogen Source for the Synthesis of 3-Halochromones and Haloarenes
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Without employing an external oxidant, the simple synthesis of 3-halochromones and various halogenated electron-rich arenes has been realized with electrode oxidation by employing the simplest sodium halide (NaX, X = Cl, Br, I) as halogen source. This electrochemical method is advantageous for the simple and mild room temperature operation, environmental friendliness as well as broad substrate scope in both C-H bond donor and halogen source components.
- Jin, Jun,Lin, Yan,Liu, Yunyun,Wan, Jie-Ping,Wang, Chaoli
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p. 12378 - 12385
(2021/09/07)
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- Method for synthesizing 2-amino-3-chloro-5-trifluoromethylpyridine
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The invention discloses a method for synthesizing 2-amino-3-chloro-5-trifluoromethylpyridine, and belongs to the technical field of organic synthesis. Specifically, starting from 2-aminopyridine, three chemical reactions of bromination, chlorination and coupling are involved, and two organic solvents are used in the whole process; and after the three-step reaction, recrystallization treatment is carried out to obtain the high-purity 2-amino-3-chloro-5-trifluoromethylpyridine. The method is mild in reaction condition and easy to control, and the obtained product is high in purity; reaction rawmaterials and organic solvents are easy to obtain and low in price, and a new way is provided for large-scale production.
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Paragraph 0007; 0020-0021; 0026-0027; 0032-0033
(2021/02/06)
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- Synthetic method of medicinal raw material 2 and 5 - dibromopyridine
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The invention relates to the technical field of preparation of dibromopyridine, and discloses a synthetic method of a pharmaceutical raw material 2 and 5 - dibromopyridine, which comprises S1: temperature rising, 2 -aminopyridine and acetic anhydride added into a four-port flask. S2: Cooling, Step S1 The raw material reaction was completely followed by a cooling treatment, followed by stirring by adding bromoethane, heating at a heating temperature of 30 - 60 (degree) C, heating time of 20 - 40 minutes, and stirring again to obtain a mixture A. S3: Monol Bromo. To the method, raw materials can be pre-mixed, so that the raw materials can be preliminarily reacted, the reaction B effect is improved, bubbles are generated after reaction, the next crystallization is facilitated, cost can be reduced through accurate control of temperature and raw materials in the process, and the method is safer and more reliable.
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Paragraph 0018; 0021; 0024
(2021/10/05)
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- Preparation method 2-5 - dibromopyridine
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The invention relates to the technical field of preparation of dibromopyridine, and discloses 2-5 - dibromopyridine preparation method which comprises the following steps S1: mixing reaction, putting 2 - aminopyridine into a reactor, adding acetone, adding bromate and N -bromosuccinimide. S2: Acetone was recovered, acetone was recovered by distillation under reduced pressure, and then filtered to collect the remaining solid. S3: The finished product was prepared, the collected remaining solids were placed in a reactor, and then sodium hydroxide solution was added followed by stirring to obtain 2 - amino -5 - bromopyridine. By adding N - bromosuccinimide and heating in batches, the reaction efficiency of N - bromosuccinimide is improved, the use amount is reduced, the cost is reduced, the raw materials can be recycled by recycling acetone, the cost is reduced, 2 - amino -5 - bromopyridine yield and the purity can be improved.
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Paragraph 0017-0025
(2021/09/21)
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- Method for synthesizing 2-amino-5-bromopyridine under synergistic effect of microwave and ionic liquid catalysis
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The invention belongs to the technical field of synthesis of 2-amino-5-bromopyridine, and particularly relates to a method for synthesizing 2-amino-5-bromopyridine under synergistic effect of microwave and ionic liquid catalysis, which comprises the following steps: adding 2-aminopyridine serving as a raw material into an organic solvent, and adding bromine under the action of an ionic liquid catalyst and microwave radiation to perform halogenation; and carrying out vacuum distillation on the obtained reaction solution to remove the solvent, and further recrystallizing to obtain the high-purity 2-amino-5-bromopyridine. Compared with the prior art, the method has the advantages that the production process is simplified, the reaction conditions are mild, the product purity is higher, meanwhile, the Lewis acidic ionic liquid can be recycled, and the production cost is low.
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Paragraph 0021-0026
(2020/06/09)
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- Synthesis method of 2, 5-dibromopyridine
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The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of 2, 5-dibromopyridine, and the method comprises the following steps: (1) adding 2-aminopyridine and acetic anhydride into a four-neck flask, refluxing, and completely reacting by thin-layer chromatography tracking; (2) when the temperature of the reaction solution in the step (1) isreduced to 20-25 DEG C, dropwise adding liquid bromine, reacting for 2-3 hours at 45-55 DEG C after completion of the dropwise adding, adding water into the system until all solids are dissolved, dropwise adding a sodium hydroxide solution, continuously reacting for 30-40 minutes when a large amount of precipitate is generated, and carrying out suction filtration, drying and recrystallization to obtain 2-amino-5-bromopyridine; and (3) adding the 2-amino-5-bromopyridine into a hydrogen bromide solution, dropwise adding a sodium nitrate solution in the presence of a catalytic amount of cuprous bromide, controlling the temperature to be -5 to15 DEG C, and reacting for 2-5 hours to obtain the 2, 5-dibromopyridine. The method has the beneficial effects of mild reaction conditions, high yield, accessible raw materials, lower cost and fewer product byproducts, reduces the composite load of later separation, and has industrial prospects.
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- Commercially Available CuO Catalyzed Hydrogenation of Nitroarenes Using Ammonia Borane as a Hydrogen Source
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Tandem ammonia borane dehydrogenation and nitroarenes hydrogenation has been reported as a novel strategy for the preparation of aromatic amines. However, the practical application of this strategy is subjected to the high-cost and tedious preparation of supported noble metal nanocatalysts. The commercially available CuO powder is herein demonstrated to be a robust catalyst for hydrogenation of nitroarenes using ammonia borane as a hydrogen source under mild conditions. Numerous amines (even sterically hindered, halogenated, and diamines) could be obtained through this method. This monometallic catalyst is characteristic of support-free, excellent chemoselectivity, low-cost, and high recyclability, which will favor its future utilization in preparative reduction chemistry. Mechanistic studies are also carried out to clarify that diazene and azoxybenzene are key intermediates of this heterogeneous reduction.
- Du, Jialei,Chen, Jie,Xia, Hehuan,Zhao, Yiwei,Wang, Fang,Liu, Hong,Zhou, Weijia,Wang, Bin
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p. 2426 - 2430
(2020/03/30)
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- Synergy of Anodic Oxidation and Cathodic Reduction Leads to Electrochemical C—H Halogenation
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We herein uncovered an electrochemical C—H halogenation protocol that synergistically combines anodic oxidation and cathodic reduction for C—X bond formation. The reaction was demonstrated under exogenous-oxidant-free conditions. Moreover, this is the first example of activating CBr4, CHBr3, and CCl3Br under electrochemical conditions.
- Zhou, Zhilin,Yuan, Yong,Cao, Yangmin,Qiao, Jin,Yao, Anjin,Zhao, Jing,Zuo, Wanqing,Chen, Wenjie,Lei, Aiwen
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supporting information
p. 611 - 615
(2019/05/10)
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- A 2 - amino -5 - bromo pyridine preparation method
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The invention belongs to the field of organic synthetic technology, in particular to a 2 - amino - 5 - bromo pyridine of the preparation method, the reaction steps are as follows: in order to 2 - aminopyridine as raw material, in order to dichloromethane or chloroform as the solvent, with the phenyl trimethyl tri bromide in 20 - 50 °C reaction at a temperature of 1 - 3 hours, the 2 - aminopyridine with phenyl trimethyl tri bromide molar ratio of 0.7 - 1.4. The technical scheme of the invention has the advantages of: (1) avoid the traditional preparation method a large number of 3 bit generation of by-products, to reduce a waste of materials and the later separation of the load; (2) the raw material 2 - aminopyridine is easy, and the cost is low, the line mild reaction conditions, high yield, the whole process does not 3 bit by-product generation, and has industrial prospects.
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Paragraph 0017-0023
(2019/05/28)
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- Selectfluor-promoted regioselective chlorination/bromination of 2-aminopyridines and 2-aminodiazines using LiCl/LiBr
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Using LiCl as a chlorine source, the chlorination of 2-aminopyridines or 2-aminodiazines in the presence of Selectfluor and DMF is established under mild conditions. This method gives chlorinated pyridines or diazines in good to high yields with high regioselectivities. Also, this method is extended to the bromination of 2-aminopyridines or 2-aminodiazines by using LiBr. The regioselectivity of the chlorination reaction is strongly dependent upon the substituent pattern in either the 2-aminopyridines or 2-aminodiazines. The synthesis of Buparlisib from chlorinated pyridines was explored. A study of the mechanism revealed that this chlorination occurs via either a pyridine or diazine radical process.
- Hu, Jiao,Zhou, Gang,Tian, Yawei,Zhao, Xiaoming
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supporting information
p. 6342 - 6345
(2019/07/10)
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- Cu-mediated selective bromination of aniline derivatives and preliminary mechanism study
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A simple and efficient bromination of aniline, aniline derivatives, and analogs have been developed. Forty three examples were given and the highest yield reached was 98%. Different substrates including substituted aniline, pyridin-amine, N-substituted aniline, N,N-disubstituted aniline, N-phenyl-amide, N-phenyl-sulfonamide, and nitrogen-containing heterocycles were all reactive and selectively generated desired bromo-products. The method can be applied to synthesize drug intermediate and quinoxaline derivatives.
- Zhao, Hong-Yi,Yang, Xue-Yan,Lei, Hao,Xin, Minhang,Zhang, San-Qi
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supporting information
p. 1406 - 1415
(2019/05/01)
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- Electrochemical Regioselective Bromination of Electron-Rich Aromatic Rings Using n Bu 4 NBr
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Electrochemical regioselective bromination of electron-rich aromatic rings using stoichiometric tetrabutylammonium bromide (n Bu 4 NBr) has been accomplished under mild conditions. This protocol provides an environmentally friendly and simple way for the construction of C-Br bond in moderate to high yields with wide functional group tolerance.
- Bai, Ya,Che, Xin,Liu, Nian,Ning, Shulin,Shi, Lingling,Wang, Shutao,Wang, Siyu,Xiang, Jinbao,Xie, Wenxia
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supporting information
p. 1313 - 1316
(2019/06/20)
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- A 2, 5 - dibromo pyridine synthesis method
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The invention belongs to the field of organic synthetic technology, in particular to a 2, 5 - dibromo pyridine synthesis method, comprises the following steps: (1) the 2 - aminopyridine and acetic anhydride is added to the four flasks reflux, thin-layer chromatography tracking reaction is complete; (2) step (1) of reaction fluids in a temperature drop to 20 - 25 °C when, [...], paused, 45 - 55 °C reaction 2 - 3 hours, water is added to the system to all the solid dissolved, sodium hydroxide solution, a large amount of precipitation of the reaction to continue 30 - 40 minutes, filtered, drying, by recrystallization to obtain 2 - amino - 5 - bromo pyridine; (3) the 2 - amino - 5 - bromo pyridine is added in a solution of hydrogen bromide, in the presence of a catalytic amount of cuprous bromide, dropping sodium nitrate solution, temperature control in the - 5 - 15 °C, reaction 2 - 5 hours, shall be 2, 5 - dibromo pyridine. The method of the invention is beneficial effect: mild reaction conditions, high yield, and raw materials are easy, and the cost is low, few by-products of the product, reduces the later separation of the composite load, has industrialized prospect.
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- Utilization of a Hydrogen Source from Renewable Lignocellulosic Biomass for Hydrogenation of Nitroarenes
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Exploring of hydrogen source from renewable biomass, such as glucose in alkaline solution, for hydrogenation reactions had been studied since 1860s. According to proposed pathway, only small part of hydrogen source in glucose was utilized. Herein, the utilization of a hydrogen source from renewable lignocellulosic biomass, one of the most abundant renewable sources in nature, for a hydrogenation reaction is described. The hydrogenation is demonstrated by reduction of nitroarenes to arylamines in up to 95 % yields. Mechanism studies suggest that the hydrogenation occurs via a hydrogen transformation pathway.
- Tan, Fang-Fang,Tang, Kai-Li,Zhang, Ping,Guo, Yan-Jun,Qu, Mengnan,Li, Yang
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p. 4189 - 4195
(2019/03/07)
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- Simple 2-amino-5-halogenated pyridine preparation method
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The invention provides a 2-amino-5-halogenated pyridine preparation method, which comprises: carrying out an addition reaction on 4-cyano-1-butyne and a halogen element X2 in a solvent under the catalysis of an acidic catalyst to obtain 4,4,5,5-tetrahalogenated n-valeronitrile, and carrying out cyclization on the 4,4,5,5-tetrahalogenated n-valeronitrile and ammonia through pyridine to obtain 2-amino-5-halogenated pyridine. According to the present invention, the preparation method has advantages of mild preparation condition, safety, environmental protection, low cost, high selectivity, less by-products and high product yield, and is suitable for industrial production.
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Paragraph 0033-0036
(2019/10/01)
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- Preparation method of 2-amino substituted six-membered nitrogen-containing heterocycle complex
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The invention discloses a preparation method of a 2-amino substituted six-membered nitrogen-containing heterocycle complex. The preparation method comprises the following steps: mix 2-fluorine substituted six-membered nitrogen-containing heterocycle complex and amidine hydrochloride salt compound, and then react under the action of a alkaline substance to obtain a 2-amino substituted six-memberednitrogen-containing heterocycle complex. Preferably, the 2-amino substituted six-membered nitrogen-containing heterocycle complex is a 2-amino pyridine compound, a 2-aminopyrimidine compound or a 2-aminopyrazine compound. Compared with the prior art, the method has the advantages of simple synthesis conditions, less reaction steps, mild reaction conditions, low cost of the catalyst used, less waste discharge and good functional group tolerance.
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Paragraph 0073; 0074
(2019/02/08)
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- Preparation method of 2-amino-5-bromopyridine
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The invention discloses a preparation method of 2-amino-5-bromopyridine. The preparation method is characterized in that 2-aminopyridine is used as the raw material, and two different bromination agents, namely bromine and N-bromo-succinimide (NBS), are sequentially added; the reaction temperature is strictly controlled, and thus 2-amino-5-bromopyridine can be quickly prepared with high yield andhigh purity; and the preparation method is applicable to industrial production. Additionally, a high-purity by-product, namely succinimide, is separated out in the preparation process and is brominated into high-purity NBS through potassium bromide, potassium bromate and sulfuric acid; and the NBS is applied to the synthesizing of 2-amino-5-bromopyridine in the method and has the same effect as the commercial NBS. According to the method, the quantity of used NBS is decreased, the raw material conversion rate is increased, and the bromination agents are recycled, so that the cost is greatly decreased; the main byproduct is only inorganic salt potassium sulfate; and the synthesizing method is green and environmentally friendly.
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Paragraph 0017; 0018; 0019; 0020; 0021; 0022
(2018/04/01)
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- Preparation method of 5-bromo-7-azaindole
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The invention belongs to the technical field of preparation of pharmaceutical intermediates and particularly relates to a preparation method of 5-bromo-7-azaindole. The target product, 5-bromo-7-azaindole, is prepared by: subjecting 2-aminopyridine as a raw material to bromination to obtain 5-bromo-2-aminopyridine, subjecting 5-bromo-2-aminopyridine to iodination to obtain 5-bromo-3-iodo-2-aminopyridine, subjecting 5-bromo-3-iodo-2-aminopyridine Sonogashira coupling and deprotection reaction to obtain 5-bromo-3-alkynyl-2-aminopyridine, and carrying out intramolecular ring-closing reaction. Thepreparation method herein has the advantages of low cost, good access to materials, good implementing convenience of reaction conditions, good operation simplicity and the like; the finished 5-bromo-7-azaindole prepared by means of the preparation method has purity of 99.3% and above.
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Paragraph 0017-0019
(2019/01/14)
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- Transition-metal-free access to 2-aminopyridine derivatives from 2-fluoropyridine and acetamidine hydrochloride
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Under catalyst-free conditions, an efficient method for the synthesis of 2-aminopyridine derivatives through the nucleophilic substitution and hydrolysis of 2-fluoropyridine and acetamidine hydrochloride has been developed. This amination uses inexpensive acetamidine hydrochloride as the ammonia source and has the advantages of a high yield, high chemoselectivity and wide substrate adaptability. The results suggest that other N-heterocycles containing fluorine substituents can also complete the reaction via these reaction conditions and yield the target products.
- Li, Yibiao,Huang, Shuo,Liao, Chunshu,Shao, Yan,Chen, Lu
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supporting information
p. 7564 - 7567
(2018/11/02)
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- pyrimidine derivatives substituted with aryl- or heteroaryl- substituted fluorene group, and organic electroluminescent device including the same
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Aryl group or a heteroaryl group substituted pyrimidine derivatives of formula 1 is coupled to polyarylenic backbone containing encoded ball number. [Formula 1] [In said formula 1, Ar1 And Ar2 Are each independently a hydrogen, methyl or phenyl, The C L6 - C24 C aryl of reflector3 - C24 It will be biting and heteroatoms, N is an integer 0 or 1 and, Ar3 The C6 - C30 C aryl of reflector3 - C30 A variety of printers] (by machine translation)
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Paragraph 0106; 0107; 0108; 0109
(2017/10/28)
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- Fused phenanthridine derivatives substituted with aryl or heteroaryl, and organic electroluminescent device including the same
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Aryl group or a heteroaryl group substituted [...] phenanthridine derivatives of formula 1 to ball number encoded. [Formula 1] [In said formula 1, Ar1 Is phenyl or pyridyl [...], Z1 And the O or S, L is a phenyl or pyridyl [...], Ar2 To is selected from the group represented by either formula 3] [Formula 3] , , , , (by machine translation)
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Paragraph 0384-0387
(2018/03/28)
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- Substituted ring compound and its method and use thereof
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The invention provides a substituted cyclic compound as well as a use method and application thereof. The compound is a compound as shown in a formula (I) or stereoisomers, stereomers, tautomers, nitric oxides, solvates, metabolites and pharmaceutically acceptable salts or prodrugs of the compound as shown in the formula (I). The invention further provides a medicament composition containing the compound. The compound and the medicament composition are capable of regulating the activity of protein kinase in a biological sample body and are used for protecting, treating or relieving proliferative diseases of patients. The formula (I) is as shown in the specification.
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Paragraph 0547; 0548; 0549
(2017/08/25)
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- Water as a hydrogen source in palladium-catalyzed reduction and reductive amination of nitroarenes mediated by diboronic acid
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An unprecedented palladium-catalyzed chemoselective reduction and reductive amination of nitroarenes with water as a hydrogen source mediated by diboronic acid have been discovered. A series of aryl amines containing various reducible functional groups were obtained in good to excellent yields.
- Zhou, Yanmei,Zhou, Haifeng,Liu, Sensheng,Pi, Danwei,Shen, Guanshuo
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p. 3898 - 3904
(2017/06/13)
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- Sustainable and Scalable Fe/ppm Pd Nanoparticle Nitro Group Reductions in Water at Room Temperature
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An operationally simple and general process for the safe and selective reduction of nitro groups utilizing ppm Pd supported on Fe nanomaterials in aqueous solution of designer surfactant TPGS-750-M has been developed and successfully carried out at a 100 mmol scale. Preferred use of KBH4 as the hydride source, at ambient temperature and pressure, lends this process suitable for a standard reaction vessel alleviating the need for specialized hydrogenation equipment. Calorimetry data parallel those expected for a classical nitro group reduction when measuring the heat of reaction (-896 to -850 kJ/mol).
- Gabriel, Christopher M.,Parmentier, Michael,Riegert, Christian,Lanz, Marian,Handa, Sachin,Lipshutz, Bruce H.,Gallou, Fabrice
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p. 247 - 252
(2017/02/26)
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- Synthesis and evaluation of the anticoccidial activity of trifluoropyrido[1,2-a]pyrimidin-2-one derivatives
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Screening of our chemical library to discover new molecules exhibiting in vitro activity against the invasion of host cells by Eimeria tenella revealed a lead compound with an IC50 of 15 μM. Structure-activity relationship studies were conducted with 34 newly synthesized compounds to identify more active molecules and enhance in vitro activity against the parasite. Four compounds were more effective in inhibiting MDBK cell invasion in vitro than the lead compound.
- Silpa, Laurence,Niepceron, Alisson,Laurent, Fabrice,Brossier, Fabien,Pénichon, Mélanie,Enguehard-Gueiffier, Cécile,Abarbri, Mohamed,Silvestre, Anne,Petrignet, Julien
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supporting information
p. 114 - 120
(2015/12/18)
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- Method for preparing organic bromide by using micro-channel reactor
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The invention discloses a method for preparing an organic bromide by using a micro-channel reactor. The method comprises the step of: performing a bromination reaction on a homogeneous solution formed by a compound shown in a formula I and a solvent and a homogeneous solution formed by a bromination agent and a solvent in the micro-channel reactor to obtain the organic bromide represented by a formula II, wherein the bromination reaction time is 1-10 minutes; the bromination reaction temperature is DEG C to 60 DEG C. The preparation method disclosed by the invention is extremely short, accurate to control reaction condition, high in safety and suitable for quick preparation of products, can be used for continuously production, and is low in cost. Moreover, by using the micro-channel reactor to prepare the organic bromide, the selectivity of reaction raw materials is high and the purity of a targerted compound is good, so that the preparation method is suitable for industrial production on a large scale. R1-H-R1-BrI II.
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Paragraph 0056; 0057; 0058; 0059; 0060
(2016/11/28)
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- 2-aminopyridine derivative containing 2-pyridone ring side chain, preparation and application
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The invention provides a 2-aminopyridine derivative containing a 2-pyridone ring side chain or an enantiomer of the 2-aminopyridine derivative. The target compound is obtained mainly by taking 2-aminopyridine as a parent nucleus to be coupled with a 4-bromo-2-pyridone ring. Experiments prove that the 2-aminopyridine derivative has a significant proliferation inhibition effect on tumor cells Karpas 299 (NPM-ALK positive cell lines) related to the ALK tyrosine kinase activity, NCI-H2228 (EML4-ALK positive cell lines), SKN-BE2 (ALK gene amplification cell lines) and SH-SY5Y (ALK F1174 mutant cell lines) and can be prepared into corresponding anti-tumor-cell drugs. The 2-aminopyridine derivative has a general structural formula I (please see the formula in the description).
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Paragraph 0083
(2017/01/02)
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- Double Sonogashira reactions on dihalogenated aminopyridines for the assembly of an array of 7-azaindoles bearing triazole and quinoxaline substituents at C-5: Inhibitory bioactivity against Giardia duodenalis trophozoites
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The synthesis of 2,3,5-trisubstituted 7-azaindoles as well as 2,5-disubstituted 7-azaindoles from 3,5-dihalogenated 2-aminopyridines is outlined. Using a double Sonogashira coupling reaction on 2-amino-3,5-diiodopyridine followed by the Cacchi reaction the synthesis of 2,3,5-trisubstituted 7-azaindoles was accomplished. In addition, using two sequential Sonogashira coupling reactions on 2-amino-5-bromo-3-iodopyridine and a potassium t-butoxide mediated ring closure reaction resulted in the assembly of 2,5-disubstituted 7-azaindoles. The 5-alkynyl substituent of the azaindole was easily converted into both quinoxaline and triazole substituents, the latter utilizing an alkyne-azide cycloaddition reaction. Some of these azaindole derivatives showed very promising biological activity against the gastrointestinal protozoal parasite Giardia duodenalis.
- Leboho, Tlabo C.,Giri, Somnath,Popova, Inessa,Cock, Ian,Michael, Joseph P.,De Koning, Charles B.
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p. 4943 - 4951
(2015/08/03)
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- USE OF THERMALLY-TREATED SUPPORTED COBALT CATALYSTS COMPRISING A POLYCYCLIC AROMATIC STRUCTURE CONSISTING OF NITROGEN LIGANDS FOR HYROGENATING AROMATIC NITRO COMPOUNDS
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The invention relates to the use of thermally-treated supported cobalt catalysts for hydrogenating aromatic nitro compounds, the cobalt catalysts having been prepared by in situ immobilization of a cobalt-amine complex on an inorganic porous support and subsequent pyrolysis, and, in the cobalt-amine complex used, cobalt being present bonded to an aromatic or heterocyclic nitrogen ligand L, the nitrogen ligand being selected so as to form a polyaromatic structure with the cobalt atom.
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Paragraph 0034; 0035
(2015/11/16)
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- Highly selective transfer hydrogenation of functionalised nitroarenes using cobalt-based nanocatalysts
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Anilines are important feedstock for the synthesis of a variety of chemicals such as dyes, pigments, pharmaceuticals and agrochemicals. The chemoselective catalytic reduction of nitro compounds represents the most important and prevalent process for the manufacture of functionalized anilines. Consequently, the development of selective catalysts for the reduction of nitro compounds in the presence of other reducible groups is a major challenge and is crucial. In this regard, herein we show that the cobalt oxide (Co3O4-NGr@C) based nano-materials, prepared by the pyrolysis of cobalt-phenanthroline complexes on carbon constitute highly selective catalysts for the transfer hydrogenation of nitroarenes to anilines using formic acid as a hydrogen source. Applying these catalysts, a series of structurally diverse and functionalized nitroarenes have been reduced to anilines with unprecedented chemo-selectivity tolerating halides, olefins, aldehyde, ketone, ester, amide and nitrile functionalities.
- Jagadeesh, Rajenahally V.,Banerjee, Debasis,Arockiam, Percia Beatrice,Junge, Henrik,Junge, Kathrin,Pohl, Marga-Martina,Radnik, J?rg,Brückner, Angelika,Beller, Matthias
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supporting information
p. 898 - 902
(2015/03/04)
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- Discovery and optimization of a highly efficacious class of 5-aryl-2-aminopyridines as FMS-like tyrosine kinase 3 (FLT3) inhibitors
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Based on a putative binding mode of quizartinib (AC220, 1), a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor in Phase III clinical development, we have designed de novo a simpler aminopyridine-based hinge binding motif. Further optimization focusing on maximizing in vivo efficacy and minimizing CYP3A4 time-dependent inhibition resulted in a highly efficacious compound (6s) in tumor xenograft model for further preclinical development.
- Liu, Gang,Abraham, Sunny,Liu, Xing,Xu, Shimin,Rooks, Allison M.,Nepomuceno, Ron,Dao, Alan,Brigham, Daniel,Gitnick, Dana,Insko, Darren E.,Gardner, Michael F.,Zarrinkar, Patrick P.,Christopher, Ron,Belli, Barbara,Armstrong, Robert C.,Holladay, Mark W.
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p. 3436 - 3441
(2015/08/11)
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- A mild method for the regioselective bromination of 2-aminopyridines
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An efficient and regioselective bromination of 2-aminopyridines was developed. The environmental friendly bromination occurs under mild and clean conditions using readily available 1-butylpyridinium bromide as the bromine source and hydrogen peroxide as the green oxidant.
- Xu, Tong,Zhou, Wen,Wang, Jing,Li, Xue,Guo, Jun-Wen,Wang, Bin
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supporting information
p. 5058 - 5061
(2015/01/08)
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- SPIRO-SUBSTITUTED OXINDOLE DERIVATIVES HAVING AMPK ACTIVITY
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The present invention relates to compounds of formula (I), which have valuable pharmacological properties, in particular are activators of AMPK and which are therefore useful in the treatment of certain disorders that can be prevented or treated by activation of this receptor. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.
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Page/Page column 107
(2015/01/07)
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- OLEFIN SUBSTITUTED OXINDOLES HAVING AMPK ACTIVITY
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The present invention relates to compounds of formula (I), which have valuable pharmacological properties, in particular are activators of AMPK and which are therefore useful in the treatment of certain disorders that can be prevented or treated by activation of this receptor. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.
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Page/Page column 102
(2015/01/07)
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- SUBSTITUTED CYCLIC COMPOUNDS AND METHODS OF USE
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The present invention provides novel substituted alkynyl compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 0221
(2014/06/24)
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- Improved synthesis of pyridyl-biaryl ring systems via benzidine rearrangements
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The acid-catalyzed benzidine rearrangement of diazo compounds is known to involve several rearrangements with the major pathway being a [5,5] sigmatropic rearrangement to provide 4,4′-diaminobiaryls. A limitation of this rearrangement has been poor conversions with pyridyl systems. Herein, we address this long standing issue to furnish hetero-biaryls via a pyridinium salt in the presence of trimethylsilyl iodide.
- Leung, Gulice Y.C.,William, Anthony D.,Johannes, Charles W.
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supporting information
p. 3950 - 3953
(2014/07/08)
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- SULFONAMIDE COMPOUNDS AND USES AS TNAP INHIBITORS
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Described herein are compounds that modulate the activity of TNAP. In some embodiments, the compounds described herein inhibit TNAP. In certain embodiments, the compounds described herein are useful in the treatment of conditions associated with hyper- mineralization.
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Paragraph 00588-00589
(2013/09/12)
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- Controlling molecular tautomerism through supramolecular selectivity
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We have isolated the stable as well as the metastable tautomers of 1-deazapurine in the solid state by exploiting principles of supramolecular selectivity in the context of cocrystal design.
- Epa, Kanishka,Aakeroey, Christer B.,Desper, John,Rayat, Sundeep,Chandra, Kusum Lata,Cruz-Cabeza, Aurora J.
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p. 7929 - 7931
(2013/09/02)
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- A facile, regioselective and controllable bromination of aromatic amines using a CuBr2/Oxone system
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A combination of cupric bromide and Oxone serves as a facile, mild and effective reagent for the bromination of aromatic amines. Primary, secondary and tertiary aromatic amines are all suitable substrates. The reaction possesses high regioselectivity and functional group tolerance, and mono- and multi-brominated products can be obtained controllably in moderate to excellent yields. The Royal Society of Chemistry 2013.
- Li, Xin-Le,Wu, Wei,Fan, Xin-Heng,Yang, Lian-Ming
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p. 12091 - 12095
(2013/09/02)
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- Integrated structure-based activity prediction model of benzothiadiazines on various genotypes of HCV NS5b polymerase (1a, 1b and 4) and its application in the discovery of new derivatives
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This work presents the first structure-based activity prediction model for benzothiadiazines against various genotypes of HCV NS5b polymerase (1a, 1b and 4).The model is a comprehensive workflow of structure-based field template followed by guided docking. The field template was used as a pre-filter and a tool to provide hits in good orientation and position. It was created based on detailed molecular interaction field analysis which includes Topomer CoMFA, grid independent analysis and Superstar. On the other hand, Guided docking was used as a refinement and assessment tool. It was actively directed by two scores: Moldock score as an interaction descriptor (r2 = 0.65) and a template similarity score as a measure for accurate binding-mode compliance. The docking template was based on energy-based pharmacophore analysis. The whole procedure was formulated and tweaked for both screening (ROC of AUC = 0.91) and activity prediction (r2 of 0.8) for the genotype 1a. In order to widen the model scope, linear interaction energy was used as a tool for predicting activities of other genotypes based on the docked ligand poses while mutation binding energy was used to investigate the effect of each amino acid mutation in genotype 4. The model was applied for structure-based fragment hopping by screening a library designed by reaction enumeration. A top scoring hit was used to generate a focused library such that it has lower TPSA than the original class ligands and thus better pharmacokinetic properties. After that, experimental validation was carried out by the synthesis of this library and its biological evaluation which yielded compounds that exhibit EC50 ranging from 1.86 to 23 μM.
- Ismail, Mohamed A.H.,Abou El Ella, Dalal A.,Abouzid, Khaled A.M.,Mahmoud, Amr H.
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experimental part
p. 2455 - 2478
(2012/05/05)
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- Preparation of highly reactive pyridine- and pyrimidine-containing diarylamine antioxidants
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We recently reported a preliminary account of our efforts to develop novel diarylamine radical-trapping antioxidants (Hanthorn, J. J. et al. J. Am. Chem. Soc. 2012, 134, 8306-8309) wherein we demonstrated that the incorporation of ring nitrogens into diphenylamines affords compounds which display a compromise between H-atom transfer reactivity to peroxyl radicals and stability to one-electron oxidation. Herein we provide the details of the synthetic efforts associated with that report, which have been substantially expanded to produce a library of substituted heterocyclic diarylamines that we have used to provide further insight into the structure-reactivity relationships of these compounds as antioxidants (see the accompanying paper, DOI: 10.1021/jo301012x). The diarylamines were prepared in short, modular sequences from 2-aminopyridine and 2-aminopyrimidine wherein aminations of intermediate pyri(mi)dyl bromides and then Pd-catalyzed cross-coupling reactions of the amines and precursor bromides were the key steps to yield the diarylamines. The cross-coupling reactions were found to proceed best with Pd(η3-1-PhC3H 4)(η5-C5H5) as precatalyst, which gave higher yields than the conventional Pd source, Pd2(dba) 3.
- Hanthorn, Jason J.,Valgimigli, Luca,Pratt, Derek A.
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experimental part
p. 6908 - 6916
(2012/10/08)
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- SUBSTITUTED DIARYLAMINES AND USE OF SAME AS ANTIOXIDANTS
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The present invention relates to substituted heteroaromatic dianlamine compounds of Formula I and II, their pharmaceutically acceptable salts, and compositions thereof useful as antioxidants, wherein each of X, Y and Z are independently a carbon or nitrogen atom; R1 and R2 are each independently a hydrogen or an electron donating group, but are not both hydrogen, and wherein R1 and R2 are each bonded to a carbon atom in their own respective aryl ring.
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Page/Page column 45-46
(2013/02/28)
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- Design and synthesis of active site inhibitors of the human farnesyl pyrophosphate synthase: Apoptosis and inhibition of ERK phosphorylation in multiple myeloma cells
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Human farnesyl pyrophosphate synthase (hFPPS) controls intracellular levels of FPP and post-translational prenylation of small GTPase proteins, which are essential for cell signaling and cell proliferation. Clinical investigations provide evidence that N-BP inhibitors of hFPPS are disease modifying agents that improve survival of multiple myeloma (MM) patients via mechanisms unrelated to their skeletal effects. A new series of N-BPs was designed that interact with a larger portion of the GPP subpocket, as compared to the current therapeutic drugs, and rigidify the 364KRRK367 tail of hFPPS in the closed conformation in the absence of IPP. An analogue of this series was used to demonstrate inhibition of the intended biological target, resulting in apoptosis and down-regulation of ERK phosphorylation in human MM cell lines.
- Lin, Yih-Shyan,Park, Jaeok,De Schutter, Joris W.,Huang, Xian Fang,Berghuis, Albert M.,Sebag, Michael,Tsantrizos, Youla S.
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body text
p. 3201 - 3215
(2012/05/20)
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