- Carbon Atom Insertion into Pyrroles and Indoles Promoted by Chlorodiazirines
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Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores, respectively. By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, the traditional haloform-based protocol central to the parent Ciamician-Dennstedt rearrangement can be modified to directly afford 3-(hetero)arylpyridines and quinolines. Chlorodiazirines are conveniently prepared in a single step by oxidation of commercially available amidinium salts. Selectivity as a function of pyrrole substitution pattern was examined, and a predictive model based on steric effects is put forward, with DFT calculations supporting a selectivity-determining cyclopropanation step. Computations surprisingly indicate that the stereochemistry of cyclopropanation is of little consequence to the subsequent electrocyclic ring opening that forges the pyridine core, due to a compensatory homoaromatic stabilization that counterbalances orbital-controlled torquoselectivity effects. The utility of this skeletal transform is further demonstrated through the preparation of quinolinophanes and the skeletal editing of pharmaceutically relevant pyrroles.
- Dherange, Balu D.,Kelly, Patrick Q.,Levin, Mark D.,Liles, Jordan P.,Sigman, Matthew S.
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supporting information
p. 11337 - 11344
(2021/08/16)
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- Palladium-Catalyzed Secondary C(sp3)?H Arylation of 2-Alkylpyridines
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A pyridyl group-assisted palladium-catalyzed secondary C(sp3)?H arylation protocol was developed. A substituent at the 3-position of the pyridyl group is proved to be important for promoting C?H arylation and controlling the regioselectivity. Aryl iodides can be used as coupling partners. The reaction proceeded in good to excellent yields with good functional group tolerance, even on the gram-scale. The preliminary asymmetric reaction was investigated using an L-proline derivative as a chiral ligand. (Figure presented.).
- Li, Hong-Liang,Kuninobu, Yoichiro
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supporting information
p. 2637 - 2641
(2020/06/02)
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- Synthesis of 1-Amino-2 H-quinolizin-2-one Scaffolds by Tandem Silver Catalysis
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An efficient tandem cycloisomerization-amination reaction catalyzed by silver is described. This rapid and atom-economic reaction delivered 1-amino-2H-quinolizin-2-one scaffolds in high yields under mild conditions. The reaction could be extended to an asymmetric version albeit with moderate enantioselective excess of the products. In addition, the products can be easily reduced into various azabicycles containing 4-pyridones, which are important building blocks in organic synthesis.
- Min, Xiao-Long,Sun, Chao,He, Ying
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supporting information
p. 724 - 728
(2019/02/21)
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- Multi-substituted amine compound and its preparation and use (by machine translation)
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The invention belongs to the field of medical technology, in particular, the present invention provides the following formula I shown multi-substituted amine compound or its isomer or its pharmaceutically acceptable salt, ester, prodrug or hydrate, its pharmaceutical composition, preparation method thereof and its use in the preparation of medicine for treating aids in use. The compound or pharmaceutical composition containing the compound can be used as an inhibitor for inhibiting HIV integrase with LEDGF/p75 between protein - protein interaction and HIV integrase dimerization, then can be used for the treatment of aids. . (by machine translation)
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Paragraph 0678; 0760; 0761; 0764; 0767
(2018/04/27)
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- Pd-Catalyzed Ligand-Free Synthesis of Arylated Heteroaromatics by Coupling of N-Heteroaromatic Bromides with Iodobenzene Diacetate, Iodosobenzene, or Diphenyliodonium Salts
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An efficient method for synthesizing arylated heteroaromatics has been reported via Pd-catalyzed ligand-free cross-coupling of N-heteroaromatic bromides with iodine(III) reagents under mild conditions. Iodobenzene diacetate, iodosobenzene, and diphenyliod
- Wang, Xiajun,He, Yongqin,Ren, Mengdan,Liu, Shengkang,Liu, He,Huang, Guosheng
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p. 7958 - 7962
(2016/09/09)
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- Transition-Metal-Free Regioselective Alkylation of Pyridine N-Oxides Using 1,1-Diborylalkanes as Alkylating Reagents
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Reported herein is an unprecedented base-promoted deborylative alkylation of pyridine N-oxides using 1,1-diborylalkanes as alkyl sources. The reaction proceeds efficiently for a wide range of pyridine N-oxides and 1,1-diborylalkanes with excellent regioselectivity. The utility of the developed method is demonstrated by the sequential C?H arylation and methylation of pyridine N-oxides. The reaction also can be applied for the direct introduction of a methyl group to 9-O-methylquinine N-oxide, thus it can serve as a powerful method for late-stage functionalization.
- Jo, Woohyun,Kim, Junghoon,Choi, Seoyoung,Cho, Seung Hwan
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supporting information
p. 9690 - 9694
(2016/08/10)
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- Flow synthesis of 2-methylpyridines via α-methylation
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A series of simple 2-methylpyridines were synthesized in an expedited and convenient manner using a simplified bench-top continuous flow setup. The reactions proceeded with a high degree of selectivity, producing α-methylated pyridines in a much greener fashion than is possible using conventional batch reaction protocols. Eight 2-methylated pyridines were produced by progressing starting material through a column packed with Raney nickel using a low boiling point alcohol (1-propanol) at high temperature. Simple collection and removal of the solvent gave products in very good yields that were suitable for further use without additional work-up or purification. Overall, this continuous flow method represents a synthetically useful protocol that is superior to batch processes in terms of shorter reaction times, increased safety, avoidance of work-up procedures, and reduced waste. A brief discussion of the possible mechanism(s) of the reaction is also presented which involves heterogeneous catalysis and/or a Ladenberg rearrangement, with the proposed methyl source as C1 of the primary alcohol.
- Manansala, Camille,Tranmer, Geoffrey K.
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p. 15797 - 15806
(2015/12/01)
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- Rh(III)-catalyzed decarboxylative coupling of acrylic acids with unsaturated oxime esters: Carboxylic acids serve as traceless activators
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α,β-Unsaturated carboxylic acids undergo Rh(III)-catalyzed decarboxylative coupling with α,β-unsaturated O-pivaloyl oximes to provide substituted pyridines in good yield. The carboxylic acid, which is removed by decarboxylation, serves as a traceless activating group, giving 5-substituted pyridines with very high levels of regioselectivity. Mechanistic studies rule out a picolinic acid intermediate, and an isolable rhodium complex sheds further light on the reaction mechanism.
- Neely, Jamie M.,Rovis, Tomislav
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supporting information
p. 2735 - 2738
(2014/03/21)
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- Intramolecular carbolithiation of N-allyl-ynamides: An efficient entry to 1,4-dihydropyridines and pyridines - Application to a formal synthesis of sarizotan
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We have developed a general synthesis of polysubstituted 1,4-dihydropyridines and pyridines based on a highly regioselective lithiation/6-endo-dig intramolecular carbolithiation from readily available N-allyl-ynamides. This reaction, which has been successfully applied to the formal synthesis of the anti-dyskinesia agent sarizotan, further extends the use of ynamides in organic synthesis and further demonstrates the synthetic efficiency of carbometallation reactions.
- Gati, Wafa,Rammah, Mohamed M.,Rammah, Mohamed B.,Evano, Gwilherm
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p. 2214 - 2222
(2013/02/23)
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- Ring closing and opening reactions leading to aza-polycyclic aromatic compounds
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A series of functionalized aza-polycyclic aromatic compounds were prepared by a superacid-promoted ring closing and opening reaction cascade. A reaction mechanism is proposed, which involves reactive dicationic intermediates. A key step in the conversions involves ipso protonation of an aryl group and elimination of an alkyl phenyl group.
- Kethe, Anila,Li, Ang,Klumpp, Douglas A.
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scheme or table
p. 3357 - 3360
(2012/07/16)
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- Synthesis of biaryls through a one-pot tandem borylation/Suzuki-Miyaura cross-coupling reaction catalyzed by a palladacycle
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The tricyclohexylphosphane adduct of cyclopalladated ferrocenylimine I exhibited high catalytic activity in the one-pot borylation/Suzuki-Miyaura coupling (BSC) reaction with low catalyst loading (2 mol-%). Various biaryls were obtained in good to excellent yields for 37 examples. This process was applied to aryl and heteroaryl halides (Br and Cl) containing a variety of functional groups and did not require an excess amount of phosphane ligand and the addition of the palladium catalyst in the second step. Cyclopalladated ferrocenylimine I exhibited high catalytic activity in the borylation/Suzuki- Miyaura coupling (BSC) reaction with low catalyst loading. Various unsymmetrical biaryls were obtained ingood to excellent yields in one pot. This protocol was applied to aryl and heteroaryl halides (Br and Cl) containing a variety of functional groups without adding catalyst in the second step. Copyright
- Wang, Lianhui,Cui, Xiuling,Li, Jingya,Wu, Yusheng,Zhu, Zhiwu,Wu, Yangjie
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p. 595 - 603
(2012/03/09)
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- Synthesis of the pyridinyl analogues of dibenzylideneacetone (pyr-dba) via an improved Claisen-Schmidt condensation, displaying diverse biological activities as curcumin analogues
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An efficient and easy procedure to synthesize the pyridinyl analogues of dibenzylideneacetone (pyr-dba) was developed by the condensation of substituted nicotinaldehyde and acetone in the presence of K2CO3 in toluene-EtOH-H2O solvent system. Structurally diverse pyr-dba, including quinolinyl dba, can be prepared conveniently in moderate to excellent yields under mild conditions with this method. The resulting pyr-dba functioned as the enone analogs of curcumin and efficiently inhibited the activation of NF-κB and the growth of colorectal carcinoma HCT116 p53+/+ cells as well as the HIV-1 IN-LEDGF/p75 interaction. The Royal Society of Chemistry 2012.
- Cao, Bin,Wang, Yong,Ding, Kan,Neamati, Nouri,Long, Ya-Qiu
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experimental part
p. 1239 - 1245
(2012/03/07)
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- Double decarboxylative Claisen rearrangement reactions: Microwave-assisted de novo synthesis of pyridines
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Microwave-assisted double decarboxylative Claisen rearrangement of bis(allyl) 2-tosylmalonates provides substituted 1,6-heptadienes, which may be alkylated, and then converted into pyridines by ozonolysis followed by reaction with ammonia generated in sit
- Craig, Donald,Paina, Federica,Smith, Stephen C.
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supporting information; experimental part
p. 3408 - 3410
(2009/02/05)
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- Synthesis, rotamer orientation, and calcium channel modulation activities of alkyl and 2-phenethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3- or 6-substituted-2-pyridyl)-5-pyridinecarboxylates
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A group of racemic alkyl and 2-phenethyl 1,4-dihydro-2,6-dimethyl-3- nitro-4-(3- or 6-substituted-2-pyridyl)-5-pyridinecarboxylates (13a-q) was prepared using a modified Hantzsch reaction that involved the condensation of a 3- or 6-substituted-2-pyridinecarboxaldehyde (7a-j) with an alkyl or 2- phenethyl 3-aminocrotonate (11a-d) and nitroacetone (12). Nuclear Overhauser (NOE) studies indicated there is a significant rotamer fraction in solution where the pyridyl nitrogen is oriented above the 1,4-dihydropyridine ring, irrespective of whether a substituent is located at the 3- or 6-position. A potential H-bonding interaction between the pyridyl nitrogen free electron pair and the suitably positioned 1,4-dihydropyridine NH moiety may stablize this rotamer orientation. In vitro calcium channel antagonist and agonist activities were determined using guinea pig ileum longitudinal smooth muscle (GPILSM) and guinea pig left atrium (GPLA) assays, respectively. Compounds having an i-Pr ester substituent acted as dual cardioselective calcium channel agonists (GPLA)/smooth muscle-selective calcium channel antagonists (GPILSM), except for the C-4 3-nitro-2-pyridyl compound which exhibited an antagonist effect on both GPLA and GPILSM. In contrast, the compounds with a phenethyl ester group, which exhibited antagonist activity (IC50 = 10-5- 10-7 M range) on GPILSM, were devoid of cardiac agonist activity on GPLA. Structure-activity relationships showing the effect of a substituent (Me, CF3, C1, NO2, Ph) at the 3- or 6-position of a C-4 2-pyridyl moiety and a variety of ester substituents (Me, Et, i-Pr, PhCH2CH2-) upon calcium channel modulation are described. Compounds possessing a 3- or 6-substituted- 2-pyridyl moiety, in conjuction with an i-Pr ester substituent, are novel 1,4-dihydropyridine calcium channel modulators that offer a new drug design approach directed to the treatment of congestive heart failure and may also be useful as probes to study the structure-function relationships of calcium channels.
- Iqbal, Nadeem,Akula, Murthy R.,Vo, Dean,Matowe, Wandikayi C.,McEwen, Carol-Anne,Wolowyk, Michael W.,Knaus, Edward E.
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p. 1827 - 1837
(2007/10/03)
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- SYNTHESIS OF ALKYL-SUBSTITUTED ARYLPYRIDINES IN THE VAPOR PHASE BY THE CHICHIBABIN METHOD
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An industrial cadmium calcium phosphate catalyst was used in the syntheses of pyridine bases in the vapor phase by the Chichibabin method (condensation of carbonyl compounds with ammonia).Alkyl-substituted arylpyridines with the aryl radical at C2, C3, or C4 are formed during the condensation of aromatic aldehydes and ammonia with saturated and unsaturated aldehydes and also with methyl alkyl ketones.
- Soldatenkov, A. T.,Fedorov, V. O.,Chandra, R.,Polosin, V. M.,Mikaya, A. I.,Prostakov, N. S.
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p. 179 - 185
(2007/10/02)
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