- Access to pyridines via cascade nucleophilic addition reaction of 1,2,3-triazines with activated ketones or acetonitriles
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We studied the cascade nucleophilic addition reactions of 1,2,3-triazines with activated acetonitriles or ketones, which were used to construct highly substituted pyridines that are not easily accessed by conventional methods. The strategy addressed some structural diversity issues currently facing medicinal chemistry, and the resulting pyridines could be used as convenient precursors for the synthesis of related pharmaceuticals. In particular, our method was applied to the syntheses of the marketed drug etoricoxib and several biologically important molecules in a few steps.
- Zhang, Yuan,Luo, Han,Lu, Qixing,An, Qiaoyu,Li, You,Li, Shanshan,Tang, Zongyuan,Li, Baosheng
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supporting information
p. 393 - 396
(2020/05/18)
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- Synthetic method and applications of polysubstituted pyridine derivative
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The invention belongs to the field of organic chemical synthesis, and relates to a synthetic method and applications of a polysubstituted pyridine derivative. According to the method, a 2,3-triazine compound and a ketone compound are used as reaction substrates, and can be subjected to a one-step reaction under the action of a catalytic amount of an alkali to synthesize polysubstituted pyridine, wherein the reaction does not involve in the use of danger and controlled drugs, so that a simple, safe, efficient and environment-friendly way is provided for synthesis of polysubstituted pyridine. According to the invention, the reaction can also be used for synthesis of drug molecules, such as one-step synthesis of drug molecule etoricoxib and a derivative thereof; and the product obtained by the invention is further derivatized to obtain multiple types of pyridine functional group-containing active molecules, such as two-step synthesis of active molecules 2-SORA.
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Paragraph 0051-0053
(2020/04/22)
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- IBX-Promoted Oxidative Cyclization of N-Hydroxyalkyl Enamines: A Metal-Free Approach toward 2,3-Disubstituted Pyrroles and Pyridines
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An iodoxybenzoic acid-mediated selected oxidative cyclization of N-hydroxyalkyl enamines was developed. Through this strategy, a variety of 2,3-disubstituted pyrroles and pyridines were produced in good selectivity involving oxidation of alcohol, followed by condensation of aldehyde and α-C of enamines. Furthermore, this metal-free method has several advantages, including the use of environmentally friendly reagents, broad substrate scope, mild reaction conditions, and high efficiency.
- Gao, Peng,Chen, Huai-Juan,Bai, Zi-Jing,Zhao, Mi-Na,Yang, Desuo,Wang, Juan,Wang, Ning,Du, Lele,Guan, Zheng-Hui
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p. 7939 - 7951
(2020/07/16)
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- Transition-Metal-Free Synthesis of Pyridine Derivatives by Thermal Cyclization of N -Propargyl Enamines
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A transition-metal-free synthesis of pyridine derivatives by 6- endo - dig cyclization of N -propargyl enamines was developed. This method is environmentally friendly and is a high atom economy reaction that is easily accessed to provide pyridine derivatives in moderate to good yield by heating N -propargyl enamines in solvent without additives. The total synthesis of onychine was achieved in 51% yield in only two steps by using this method.
- Chikayuki, Yuya,Higashiyama, Kimio,Kirita, Akiko,Matsuo, Natsuko,Miyashige, Takakane,Sasaki, Shigeru,Teramoto, Hiroyoshi,Yamauchi, Takayasu,Yonekawa, Shiori
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p. 1113 - 1121
(2020/04/01)
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- Arylation, Vinylation, and Alkynylation of Electron-Deficient (Hetero)arenes Using Iodonium Salts
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Arylation, vinylation, and alkynylation of electron-deficient arenes and heteroarenes have been achieved by chemoselective C-H zincation followed by copper-catalyzed coupling reactions using iodonium salts. This approach offers a direct and general access to a wide scope of (hetero)biaryls as well as alkenylated and alkynylated heteroarenes under mild conditions. It is particularly useful and valuable for the rapid and modular synthesis of diverse (hetero)aryl compounds, as demonstrated in the synthesis of transient receptor potential vanilloid 1 (TRPV1) antagonists and angiotensin II receptor type 1 (AT1 receptor) antagonists.
- Liu, Chuan,Wang, Qiu
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supporting information
p. 5118 - 5121
(2016/10/14)
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- Inherent vs Apparent Chemoselectivity in the Kumada-Corriu Cross-Coupling Reaction
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The Kumada-Corriu reaction is a powerful tool for C-C bond formation, but is seldom utilized due to perceived chemoselectivity issues. Herein, we demonstrate that high-yielding couplings can occur in the presence of many electrophilic and heterocyclic functional groups. Our strategy is mechanically based, matching oxidative addition rates with the rate of syringe pump addition of the Grignard reagent. The mechanistic reason for the effectiveness of this strategy is uncovered by continuous-infusion ESI-MS studies.
- Hua, Xiye,Masson-Makdissi, Jeanne,Sullivan, Ryan J.,Newman, Stephen G.
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supporting information
p. 5312 - 5315
(2016/11/02)
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- Lewis acid-catalyzed borono-minisci reactions of arylboronic acids and heterocycles
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A Lewis acid-catalyzed Minisci reaction between arylboronic acids and heterocycles has been developed. This radical-coupling reaction was demonstrated employing several different heterocycles as well as electron-rich arylboronic acids. Quinoline substrates afforded modest regioselectivity for substitution at the 4-position under the reaction conditions, in contrast to previously reported Br?nsted acid-mediated reactions with quinoline substrates that favored substitution at the 2-position.
- Biaco, Joyce L.,Jones, Savannah L.,Barker, Timothy J.
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p. 1687 - 1697
(2016/10/12)
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- N-methyliminodiacetic acid as a simple and highly efficient ligand for palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl chlorides
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A simple, air-stable, inexpensive and easily prepared molecule, N-methyliminodiacetic acid (MIDA), is reported as a ligand for palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of phenylboronic acid with aryl chlorides. The yield of the corresponding Suzuki coupling reaction is up to around 90% at both high temperature of 80°C and room temperature under ambient atmosphere.
- Qi, Liang,Zhou, Xiuling,Li, Xiaogang,Li, Wei,Lv, Meiyun,Guo, Mengping
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p. 244 - 246
(2015/03/30)
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- Palladacycle-catalyzed Suzuki-Miyaura reaction of aryl/heteroaryl halides with MIDA boronates in EtOH/H2O or H2O
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With good to excellent yields, a series of mono- or diheteroaryl compounds were synthesized via the palladacycle-catalyzed Suzuki-Miyaura reaction of various N-methyliminodiacetic acid (MIDA) boronates with aryl/heteroaryl halides in EtOH/H2O or H2O. This journal is the Partner Organisations 2014.
- Li, Yabo,Wang, Jingran,Wang, Zhiwei,Huang, Mengmeng,Yan, Beiqi,Cui, Xiuling,Wu, Yusheng,Wu, Yangjie
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p. 36262 - 36266
(2014/11/08)
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- 3-Indolylphosphines as ligand for palladium in Suzuki-Miyaura coupling reaction of chloroarenes: Substituent effects
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The ligand 1,3-bis(diphenylphosphino)-1H-indole, L1 with palladium promotes Suzuki-Miyaura coupling reaction of chloroarenes and benzyl chlorides with arylboronic acids. Structural modification of L1 established that the phosphine group at C-3 position of indole was crucial to catalysis and its efficacy depended on the nature of the N-substituent. 31P chemical shift values of the substituted indolylphosphines appear to show a correlation with observed trend in catalytic efficiency.
- Saha, Debajyoti,Ghosh, Raju,Sarkar, Amitabha
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p. 3951 - 3960
(2013/06/27)
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- Ferrocenyl (P,N)-diphosphines incorporating pyrrolyl, imidazolyl or benzazaphospholyl moieties: Synthesis, coordination to group 10 metals and performances in palladium-catalyzed arylation reactions
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Three novel symmetrical ferrocenyl diphosphines with tertiary phosphorus atoms holding respectively nitrogen-containing heterocyclic derivatives of pyrrole, imidazole and benzazaphosphole were synthesized and characterized. Up to now, integration of heteroaromatic fragments, or more generally hetero-cycles, as substituents on the tertiary phosphines of symmetrical ferrocenyl diphosphines has been limited to the furyl motif. Their coordination to palladium and platinum group 10 transition metals was exemplified, and analyzed using single crystal X-ray diffraction. The performances obtained in palladium-catalyzed copper-free Sonogashira and Suzuki cross-coupling reactions using bromoarenes and chloroarenes are reported for the most efficient system. The unprecedented combination of a tert-butyl group and of an imidazolyl motif on the phosphorus atoms led to an air-stable ferrocenyl diphosphine, which allowed in combination with 0.1-0.2 mol% of palladium to generate catalytic systems able to couple some activated chloroarenes and most of the bromoarenes examined.
- Allouch, Fatima,Vologdin, Nikolay V.,Cattey, Hélène,Pirio, Nadine,Naoufal, Daoud,Kanj, Ali,Smaliy, Radomyr V.,Savateev, Aleksandr,Marchenko, Anatoly,Hurieva, Anastasia,Koidan, Heorgii,Kostyuk, Aleksandr N.,Hierso, Jean-Cyrille
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- A novel, air-stable phosphine ligand for the palladium-catalyzed suzuki-miyaura cross-coupling reaction of chloro arenes
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(Figure presented) A novel, air-stable phosphine ligand, prepared from readily available 2-bromonitrobenzene and vinylmagnesium bromide, combines with Pd(CH3CN)2Cl2 to afford an effective catalyst for Suzuki-Miyaura cross-coupling of aryl, heteroaryl, and allyl chlorides with phenylboronic acid.
- Ghosh, Raju,Adarsh,Sarkar, Amitabha
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experimental part
p. 5320 - 5322
(2010/10/19)
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- 9-Hydroxyazafluorenes and their use in thrombin inhibitors
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Optimization of a previously reported thrombin inhibitor, 9-hydroxy-9-fluorenylcarbonyl-L-prolyl-trans-4-aminocyclohexylmethylamide (1), by replacing the aminocyclohexyl P1 group provided a new lead structure, 9-hydroxy-9-fluorenylcarbonyl-L-prolyl-2-aminomethyl-5-chlorobenzylamide (2), with improved potency (Ki = 0.49 nM for human thrombin, 2× APTT = 0.37 μM in human plasma) and pharmacokinetic properties (F = 39%, iv T1/2 = 13 h in dogs). An effective strategy for reducing plasma protein binding of 2 and improving efficacy in an in vivo thrombosis model in rats was to replace the lipophilic fluorenyl group in P3 with an azafluorenyl group. Systematic investigation of all possible azafluorenyl P3 isomers and azafluorenyl-N-oxide analogues of 2 led to the identification of an optimal compound, 3-aza-9-hydroxyfluoren-9(R)-ylcarbonyl-L-prolyl-2-aminomethyl-5- chlorobenzylamide (19b), with high potency (Ki = 0.40 nM, 2× APTT = 0.18 μM), excellent pharmacokinetic properties (F = 55%, T 1/2 = 14 h in dogs), and complete efficacy in the in vivo thrombosis model in rats (inhibition of FeCl3-induced vessel occlusions in six of six rats receiving an intravenous infusion of 10 μg/kg/min of 19b). The stereochemistry of the azafluorenyl group in 19b was determined by X-ray crystallographic analysis of its N-oxide derivative (23b) bound in the active site of human thrombin.
- Stauffer, Kenneth J.,Williams, Peter D.,Selnick, Harold G.,Nantermet, Philippe G.,Newton, Christina L.,Homnick, Carl F.,Zrada, Matthew M.,Lewis, S. Dale,Lucas, Bobby J.,Krueger, Julie A.,Pietrak, Beth L.,Lyle, Elizabeth A.,Singh, Rominder,Miller-Stein, Cynthia,White, Rebecca B.,Wong, Bradley,Wallace, Audrey A.,Sitko, Gary R.,Cook, Jacquelyn J.,Holahan, Marie A.,Stranieri-Michener, Maria,Leonard, Yvonne M.,Lynch Jr., Joseph J.,McMasters, Daniel R.,Yan, Youwei
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p. 2282 - 2293
(2007/10/03)
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- Palladium Charcoal-Catalyzed Suzuki-Miyaura Coupling to Obtain Arylpyridines and Arylquinolines
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A phosphine ligand, such as PPh3 or 2-(dicyclohexylphosphino)biphenyl, is essential for the Pd/C-catalyzed Suzuki-Miyaura coupling of halopyridines and haloquinolines, although it has been reported that the reaction of phenyl chlorides can be catalyzed by nonprereduced Pd/C without any additives. In the reactions of bromopyridines, bromoquinolines, 2-chloropyridines, and 2-chloroquinolines, PPh3 was effective enough to provide coupling products in good yields. However, in the reactions of 3-chloropyridine, 4-chloropyridine, and 6-chloroquinoline, sterically hindered 2-(dicyclohexylphosphino)biphenyl was indispensable as a ligand.
- Tagata, Tsuyoshi,Nishida, Mayumi
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p. 9412 - 9415
(2007/10/03)
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