- Deoxygenation of N-oxides with triphenylphosphine, catalyzed by dichlorodioxomolybdenum(VI)
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Chemoselective deoxygenation of N-oxides was carried out under mild conditions with common phosphines in the presence of dichlorodioxomolybdenum(VI) . Georg Thieme Verlag Stuttgart.
- Sanz, Roberto,Escribano, Jaime,Fernández, Yolanda,Aguado, Rafael,Pedrosa, María R.,Arnáiz, Francisco J.
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- Cl3CCN/PPh3 and CBr4/PPh3: Two efficient reagent systems for the preparation of N-heteroaromatic halides
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Cl3CCN/PPh3 and CBr4/PPh3 are two highly reactive reagent systems for the conversion of N-heteroaromatic hydroxy compounds into N-heteroaromatic chlorides or bromides in moderate to excellent yields under mild and acid-free conditions.
- Kijrungphaiboon, Woranun,Chantarasriwong, Oraphin,Chavasiri, Wainthorn
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- POLYORGANOMETALLIC HETEROCYCLES. 2,6-DILITHIOPYRIDINE
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Metal-halogen exchange between 2,6-diiodo- and 2,6-dibromopyridine and two equivalents of n-butyllithium gives 2,6-dilithiopyridine.On quenching with either carbon dioxide followed by esterification, methanol or dimethyl disulfide the dilithio compound gives a methyl 2,6-pyridinedicarboxylate, pyridine, or 2,6-dithiomethylpyridine, respectively.A convenient procedure for halogen-halogen exchange is also described.
- Newkome, George R.,Roper, Jerry M.
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- TMSCH2Li and TMSCH2Li-LiDMAE: Efficient reagents for noncryogenic halogen-lithium exchange in bromopyridines
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(Chemical Equation Presented) TMSCH2Li and TMSCH 2Li-LiDMAE have been used efficiently for bromine-lithium exchange in 2-bromo-, 3-bromo-, and 2,5-dibromopyridines under noncryogenic conditions, while low temperatures (-78 to -100°C) are always needed with n-BuLi. The aminoalkoxide LiDMAE induced a remarkable C-2 selectivity with 2,5-dibromopyridines in toluene at 0°C, which was unprecedented at such a temperature. The lithiopyridines were successfully reacted witb electrophiles also under noncryogenic conditions giving the expected adducts in good yields.
- Doudouh, Abdelatif,Woltermann, Christopher,Gros, Philippe C.
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- A facile halogenation of some hydroxyheterocycles using triphenylphosphine and N-halosuccinimide
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Some hydroxyheterocycles were halogenated to give the corresponding haloheterocycles using triphenylphosphine and N-halosuccinimide. In comparison with the usual method using phosphorus oxyhalide, the haloheterocycles were easily isolated.
- Sugimoto, Osamu,Mori, Miho,Tanji, Ken-ichi
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- Steric Effects on the Structures, Reactivity, and Coordination Chemistry of Tris(2-pyridyl)aluminates
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Introducing substituents in the 6-position of the 2-pyridyl rings of tris(pyridyl)aluminate anions, of the type [EtAl(2-py′)3]- (py′=a substituted 2-pyridyl group), has a large impact on their metal coordination characteristics. This is seen most remarkably in the desolvation of the THF solvate [EtAl(6-Me-2-py)3Li·THF] to give the monomer [EtAl(6-Me-2-py)3Li] (1), containing a pyramidal, three-coordinate Li+ cation. Similar monomeric complexes are observed for [EtAl(6-CF3-2-py)3Li] (2) and [EtAl(6-Br-2-py)3Li] (3), which contain CF3 and Br substituents (R). This steric influence can be exploited in the synthesis of a new class of terminal Al-OH complexes, as is seen in the controlled hydrolysis of 2 and 3 to give [EtAl(OH)(6-R-2-py)2]- anions, as in the dimer [EtAl(OH)(6-Br-2-py)2Li]2 (5). Attempts to deprotonate the Al-OH group of 5 using Et2Zn led only to the formation of the zincate complex [LiZn(6-Br-py)3]2 (6), while reactions of the 6-Br substituted 3 and the unsubstituted complex [EtAl(2-py)3Li] with MeOH give [EtAl(OMe)(6-Br-2-py)2Li]2 (7) and [EtAl(OMe)(2-py)2Li]2 (8), respectively, having similar dimeric arrangements to 5. The combined studies presented provide key synthetic methods for the functionalization and elaboration of tris(pyridyl)aluminate ligands.
- García-Rodríguez, Raúl,Wright, Dominic S.
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- Titanium(0) Reagents; 2. A Selective and Efficient Deoxygenation of Halogen Containing Heteroaromatic N-Oxides
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Following successful reductions of unfunctionalized heteroaromatic N-oxides by titanium(0), we applied this method to halogenated aromatic N-oxides to give the deoxygenated halogeno derivatives in 90-95percent yield.
- Malinowski, Marek,Kaczmarek, Lukasz
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- A facile bromination of hydroxyheteroarenes
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Bromination of hydroxyheteroarenes using P2O5/Bu4NBr proceeds under mild conditions to afford high yields of various bromoheteroarenes. This procedure is successfully applied to large-scale syntheses of bromoheteroarenes.
- Kato, Yoshiaki,Okada, Shigemitsu,Tomimoto, Koji,Mase, Toshiaki
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- Clean protocol for deoxygenation of epoxides to alkenes: Via catalytic hydrogenation using gold
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The epoxidation of olefin as a strategy to protect carbon-carbon double bonds is a well-known procedure in organic synthesis, however the reverse reaction, deprotection/deoxygenation of epoxides is much less developed, despite its potential utility for the synthesis of substituted olefins. Here, we disclose a clean protocol for the selective deprotection of epoxides, by combining commercially available organophosphorus ligands and gold nanoparticles (Au NP). Besides being successfully applied in the deoxygenation of epoxides, the discovered catalytic system also enables the selective reduction N-oxides and sulfoxides using molecular hydrogen as reductant. The Au NP catalyst combined with triethylphosphite P(OEt)3 is remarkably more reactive than solely Au NPs. The method is not only a complementary Au-catalyzed reductive reaction under mild conditions, but also an effective procedure for selective reductions of a wide range of valuable molecules that would be either synthetically inconvenient or even difficult to access by alternative synthetic protocols or by using classical transition metal catalysts. This journal is
- Fiorio, Jhonatan L.,Rossi, Liane M.
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p. 312 - 318
(2021/01/29)
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- Transition-metal-free decarboxylative halogenation of 2-picolinic acids with dihalomethane under oxygen conditions
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A convenient and efficient method for the synthesis of 2-halogen-substituted pyridines is described. The decarboxylative halogenation of 2-picolinic acids with dihalomethane proceeded smoothly via N-chlorocarbene intermediates to afford 2-halogen-substituted pyridines in satisfactory to excellent yields under transition-metal-free conditions. This new type of decarboxylative halogenation is operationally simple and exhibits high functional-group tolerance.
- Zhang, Xitao,Feng, Xiujuan,Zhang, Haixia,Yamamoto, Yoshinori,Bao, Ming
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supporting information
p. 5565 - 5570
(2019/10/22)
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- Design, synthesis and biological evaluation of deuterated Vismodegib for improving pharmacokinetic properties
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Vismodegib is an oral and high selective hedgehog (Hh) inhibitor used for the treatment of basal cell carcinoma (BCC). In this work, analogs of Vismodegib with deuterium-for-hydrogen replacement at certain metabolically active sites were prepared and found to have a better pharmacokinetic properties in mice. In particular, deuterated compound SKLB-C2211 obviously altered the blood circulation behavior compared to its prototype, which was demonstrated by significantly prolonged blood circulation half-life time (t1/2) and increased AUC0→∞. These results suggested SKLB-C2211 had the potential to be a long-acting inhibitor against Hh signaling pathway, and laid the foundation for the further research of its druggability.
- Wang, Fangying,Jiang, Hongxia,Deng, Yufang,Yu, Jiang,Zhan, Miao,Zhao, Lifeng,Chen, Yuanwei
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supporting information
p. 2399 - 2402
(2018/06/25)
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- Synthesis of bromocyclopropylpyridines via the Sandmeyer reaction
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The reactions of 2-amino-5-cyclopropylpyridine with organic nitrites in the presence of copper(II) halides in various organic solvents were investigated. Optimal reaction conditions for the Sandmeyer reaction were developed and successfully applied to the synthesis of useful building blocks, bromo and chlorocyclopropylpyridines. Aminocyclopropylpyridines were synthesized in high yields from the corresponding aminobromopyridines under standard Suzuki coupling conditions.
- Striela, Romualdas,Urbelis, Gintaras,Sūd?ius, Jurgis,Ston?ius, Sigitas,Sadzevi?ien?, Rita,Labanauskas, Linas
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supporting information
p. 1681 - 1683
(2017/04/06)
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- B(C6F5)3-Catalyzed Deoxygenation of Sulfoxides and Amine N-Oxides with Hydrosilanes
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An efficient strategy for the deoxygenation of sulfoxides and amine N-oxides by using B(C6F5)3 and hydrosilanes was developed. This method provided the corresponding aromatic and aliphatic products in good to high yields and showed good functional-group tolerance under mild conditions.
- Ding, Fangwei,Jiang, Yanqiu,Gan, Shaoyan,Bao, Robert Li-Yuan,Lin, Kaifeng,Shi, Lei
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p. 3427 - 3430
(2017/07/04)
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- A disopyramide pharmaceutical intermediate 2-bromo pyridine synthesis method (by machine translation)
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A disopyramide pharmaceutical intermediate 2-bromo pyridine synthesis method, comprising the following steps: adding the reaction container 2-aminopyridine 1.3mol, O-toluene solution 1.6-1.9mol, reducing the temperature of the solution to 3-5°C, control the stirring speed 130-170rpm, adding cuprous bromide 1.5mol, cyclonexane 600 ml, reaction 90-120min, the elevated temperature to 40-45°C, to continue reaction 60-80min, by adding sodium sulfite solution 300 ml, reducing the temperature of the solution to 30-35°C, reaction 30-50min, solution with acetonitrile extraction 3-5 time, combined acetonitrile extracted solution, salt solution washing, dehydrating agent dehydration, after recovering acetonitrile, vacuum distillation, collecting 90-95 °C fraction, re-crystallization in the ethylenediamine, shall be 2-bromo pyridine. (by machine translation)
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Paragraph 0015; 0016
(2016/11/17)
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- Deoxygenation of amine N-oxides using gold nanoparticles supported on carbon nanotubes
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Deoxygenation of a variety of aromatic and aliphatic amine N-oxides has been carried out in excellent yield using dimethylphenylsilane as the reducing agent under the catalytic influence of a carbon nanotube-gold nanohybrid at room temperature. Low catalyst loading, good TON and TOF values, and recyclability of the catalyst are some of the salient features of our methodology.
- Donck, Simon,Gravel, Edmond,Shah, Nimesh,Jawale, Dhanaji V.,Doris, Eric,Namboothiri, Irishi N. N.
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p. 50865 - 50868
(2015/06/25)
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- Nitrosation of aryl and heteroaryltrifluoroborates with nitrosonium tetrafluoroborate
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Organotrifluoroborates have emerged as an alternative to toxic and air- and moisture-sensitive organometallic species for the synthesis of functionalized aryl and heteroaryl compounds. It has been shown that the trifluoroborate moiety can be easily converted into a variety of different substituents in a late synthetic stage. In this paper, we disclose a mild, selective, and convenient method for the ipso-nitrosation of organotrifluoroborates using nitrosonium tetrafluoroborate (NOBF4). Aryl- and heteroaryltrifluoroborates were converted into the corresponding nitroso products in good to excellent yields. This method proved to be tolerant of a broad range of functional groups.
- Molander, Gary A.,Cavalcanti, Livia N.
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experimental part
p. 4402 - 4413
(2012/06/18)
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- Reduction of amine N-oxides by diboron reagents
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Facile reduction of alkylamino-, anilino-, and pyridyl-N-oxides can be achieved via the use of diboron reagents, predominantly bis- (pinacolato)- and in some cases bis(catecholato)diboron [(pinB)2 and (catB)2, respectively]. Reductions occur upon simply mixing the amine N oxide and the diboron reagent in a suitable solvent, at a suitable temperature. Extremely fast reductions of alkylamino- and anilino-N-oxides occur, whereas pyridyl-N-oxides undergo slower reduction. The reaction is tolerant of a variety of functionalities such as hydroxyl, thiol, and cyano groups, as well as halogens. Notably, a sensitive nucleoside N-oxide has also been reduced efficiently. The different rates with which alkylamino- and pyridyl-N-oxides are reduced has been used to perform stepwise reduction of the N,N-dioxide of (S)-(-)-nicotine. Because it was observed that (pinB)2 was unaffected by the water of hydration in amine oxides, the feasibility of using water as solvent was evaluated. These reactions also proceeded exceptionally well, giving high product yields. In constrast to the reactions with (pinB)2, triethylborane reduced alkylamino-N oxides, but pyridine N-oxide did not undergo efficient reduction even at elevated temperature. Finally, the mechanism of the reductive process by (pinB)2 has been probed by 1H and 11B NMR. (Figure presented) ; 2011 American Chemical Society.
- Kokatla, Hari Prasad,Thomson, Paul F.,Bae, Suyeal,Doddi, Venkata Ramana,Lakshman, Mahesh K.
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experimental part
p. 7842 - 7848
(2011/12/01)
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- Flow microreactor synthesis of disubstituted pyridines from dibromopyridines via Br/Li exchange without using cryogenic conditions
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A flow microreactor method for the synthesis of disubstituted pyridines by generation of pyridyllithiums followed by reactions with electrophiles has been developed. By using a short residence time and efficient temperature control, the cryogenic conditions required for conventional batch macro processes can be avoided. Sequential introduction of two different electrophiles into dibromopyridines has been achieved using an integrated flow microreactor system composed of four micromixers and four microtube reactors, to obtain disubstituted pyridine compounds.
- Nagaki, Aiichiro,Yamada, Shigeyuki,Doi, Masatomo,Tomida, Yutaka,Takabayashi, Naofumi,Yoshida, Jun-Ichi
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supporting information; experimental part
p. 1110 - 1113
(2011/06/26)
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- One-pot iodination of hydroxypyridines
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(Chemical Equation Presented) A one-pot, high-yielding iodination of hydroxypyridines and hydroxyquinolines is described. The iodination proceeds under mild conditions, and the products are obtained in high yield without the need for chromatographic purif
- Maloney, Kevin M.,Nwakpuda, Emily,Kuethe, Jeffrey T.,Yin, Jingjun
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supporting information; experimental part
p. 5111 - 5114
(2009/10/24)
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- Bromine-lithium exchange under non-cryogenic conditions: TMSCH 2Li-LiDMAE promoted C-2 lithiation of 2,3-dibromopyridine
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The first C-2 selective bromine-lithium exchange in 2,3-dibromopyridine was performed at 0°C in toluene using the TMSCH2Li-LiDMAE reagent. The Royal Society of Chemistry.
- Gros, Philippe C.,Elaachbouni, Fatima
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scheme or table
p. 4813 - 4815
(2009/03/12)
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- Preparation of novel substituted haloarene compounds
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This invention relates to a new process for the preparation of novel substituted haloarene compounds of the formula I or IV: respectively, wherein R1, R2, R3, R4, R5, X, and Y are as defined herein, that comprises a novel and efficient selective mono-lithiation of a dihaloarene of the formula II or V: respectively, by an organo-lithium compound in the presence of a carbonyl reactant of the formula III: wherein R1 and R2 are as defined herein. In the process of the instant invention, the newly formed lithiated haloarene is sequentially quenched in situ by the carbonyl reactant to form said substituted haloarene. The process is suitable for batch or continuous flow systems. The substituted haloarenes produced by the process of the present invention are useful intermediates in the preparation of N-aryl or N-heteroaryl substituted pharmaceutically active compounds that include selective antagonists, inverse agonists and partial agonists of serotonin 1 (5-HT1) receptors useful in treating or preventing depression, anxiety, obsessive compulsive disorder (OCD) and other disorders for which a 5-HT1 agonist or antagonist is indicated.
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(2008/06/13)
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- Substituted β-alanine derivatives as cell adhesion inhibitors
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β-Alanine derivatives of Formula I are antagonists of VLA-4 and/or α4β7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of asthma, allergies, inflammation, multiple sclerosis, and other inflammatory and autoimmune disorders.
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- Silyl-mediated halogen/halogen displacement in pyridines and other heterocycles
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Heating with bromotrimethylsilane converts 2-chloropyridine into 2-bromopyridine and 2-chloro-6-methylpyridine into 2-bromo-6-methylpyridine. Both 2-chloropyridines and 2-bromopyridines give the corresponding iodo compound when treated with in situ generated iodotrimethylsilane. Although 3- and 4-chloropyridine are completely inert, 2,4-dichloropyridine undergoes the halogen/halogen exchange simultaneously at the 2- and 4-position. Halogen displacement takes place exclusively at the 2-position with 2,3-dichloropyridine and 2,5-dichloropyridine. In agreement with the intermediacy of N-trimethylsilylpyridinium salts as a prerequisite for the occurrence of halogen exchange, neither 2-fluoropyridine and 2-fluoro-6-methylpyridine nor any 2,6-dihalopyridine reacts. Finally, bromine/chlorine and iodine/chlorine substitution can also be accomplished with 2-or 4-chloroquinoline, 1-chloroisoquinoline, 2-chloropyrimidine, chloropyrazine and 2,3-dichloroquinoxaline as substrates. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2002).
- Schlosser, Manfred,Cottet, Fabrice
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p. 4181 - 4184
(2007/10/03)
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- CARBOXYLIC ACID DERIVATIVES AND DRUGS CONTAINING THE SAME
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The present invention provides a novel carboxylic acid compound, a salt thereof or a hydrate of them useful as an insulin-resistant improver, and a medicament comprising the compound as an active ingredient. That is, the present invention provides a carboxylic acid compound represented by the following formula (I), a salt thereof, an ester thereof or a hydrate of them. In the formula, R1 represents hydrogen atom, hydroxyl group or a C1-6 alkyl group etc. which may have one or more substituents; L represents a single or double bond or a C1-6 alkylene group etc. which may have one or more substituents; M represents a single bond or a C1-6 alkylene group etc. which may have one or more substituents; T represents a single bond or a C1-3 alkylene group which may have one or more substituents; W represents carboxyl group or a group represented by the formula -CON(Rw1)Rw2 (wherein Rw1 and Rw2 are the same as or different from each other and each represents hydrogen atom, formyl group etc.) etc.; represents a single or double bond; X represents oxygen atom or a C2-6 alkenylene group etc. which may have one or more substituents; Y represents a C5-12 aromatic hydrocarbon group etc. which may have one or more substituents and which may have one or more heteroatoms; and ring Z represents a C5-6 aromatic hydrocarbon group which may have 0 to 4 substituents and which may have one or more heteroatoms.
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- Substituted polycyclic aryl and heteroaryl pyridines useful for selective inhibition of the coagulation cascade
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The present invention relates to compounds, and prodrugs thereof, composition and methods useful for preventing and treating thrombotic conditions in mammals. The compounds of the present invention, and prodrugs thereof, selectively inhibit certain proteases of the coagulation cascade.
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- Synthesis of a muscarinic receptor antagonist via a diastereoselective Michael reaction, selective deoxyfluorination and aromatic metal-halogen exchange reaction
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An efficient synthesis of a structurally unique, novel M3 antagonist 1 is described. Compound 1 is conveniently disconnected retrosynthetically at the amide bond to reveal the acid portion 2 and the amine fragment 3. The synthesis of key intermediate 2 is highlighted by a ZnCl2-MAEP complex 19 catalyzed diastereoselective Michael reaction of dioxolane 7 with 2-cyclopenten-1-one (5) to establish the contiguous quaternary-tertiary chiral centers and a subsequent geminal difluorination of ketone 17 using Deoxofluor in the presence of catalytic BF3·OEt2. The synthesis of the amine moiety 3 is highlighted by the discovery of a novel n-Bu3MgLi magnesium-halogen exchange reaction for selective functionalization of 2,6-dibromopyridine. This new and practical metalation protocol obviated cryogenic conditions and upon quenching with DMF gave 6-bromo-2-formylpyridine (26) in excellent yield. Further transformations afforded the amine fragment 3 via reductive amination with 35, Pd-catalyzed aromatic amination, and deprotection. Finally, the highly convergent synthesis of 1 was accomplished by coupling of the two fragments. This synthesis has been used to prepare multi-kilogram quantities of the bulk drug.
- Mase,Houpis,Akao,Dorziotis,Emerson,Hoang,Iida,Itoh,Kamei,Kato,Kato,Kawasaki,Lang,Lee,Lynch,Maligres,Molina,Nemoto,Okada,Reamer,Song,Tschaen,Wada,Zewge,Volante,Reider,Tomimoto
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p. 6775 - 6786
(2007/10/03)
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- Application of phosphonium salts to the reactions of various kinds of amides
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The phosphonium salts 1 and 2 prepared from triphenylphosphine and N-halogenosuccinimide proved to be applicable to the conversion of amide compounds. Especially, halogenation of electron-deficient heteroaromatic alcohols with these reagents seems to be a convenient method compared to the halogenation with phosphorus oxyhalides.
- Sugimoto, Osamu,Mori, Miho,Moriya, Keisuke,Tanji, Ken-Ichi
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p. 1112 - 1118
(2007/10/03)
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- HETEROSUBSTITUTED PYRIDINE DERIVATIVES AS PDE 4 INHIBITORS
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The invention encompasses the novel compound of Formula I useful in the treatment of diseases, including asthma, by raising the level of cyclic adenosine-3',5'-monophosphate (cAMP) through the inhibition of phosphodiesterase IV (PDE 4)
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- Heterosubstituted pyridine derivatives as PDE4 inhibitors
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The invention encompasses the novel compound of Formula I useful in the treatment of diseases, including asthma, by raising the level of cyclic adenosine-3′,5′-monophosphate (cAMP) through the inhibition of phosphodiesterase IV (PDE 4). or a pharmaceutically acceptable salt or hydrate thereof. The invention also encompasses pharmaceutical compositions and methods for treatment.
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- Selective monolithiation of 2,5-dibromopyridine with butyllithium
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Selective monolithiation of 2,5-dibromopyridine at either the 2-position or the 5-position is reported. Solvent and concentration strongly influence the selectivity. Coordinating solvents and higher concentration favor the 5- position while non-coordinati
- Wang, Xin,Rabbat, Philippe,O'Shea, Paul,Tillyer, Richard,Grabowski,Reider, Paul J.
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p. 4335 - 4338
(2007/10/03)
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- Synthesis and evaluation of analgesic, antiinflammatory and antiplatelet properties of new 2-pyridylarylhydrazone derivatives
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This work describes recent results from our research program aiming at the synthesis and pharmacological evaluation of new compounds acting as antiinflammatory, analgesic and platelet antiaggregatory. In this paper the synthesis and the pharmacological profile as analgesic, antiinflammatory and anti-platelet of new functionalized 2-pyridylarylhydrazone derivatives 5a-r are discussed. This class of N-heterocyclic derivatives represents a new series of prototype candidates with analgesic and antiinflammatory properties possessing also an important anti-aggregating activity. The pharmacological results herein disclosed suggest that the anti-inflammatory and analgesic activities of these new pyridynehydrazone derivatives observed in the carrageenan pleurisy model and acetic acid writhing test, respectively, is probably due to an interference on the arachidonic acid (AA) metabolism. The most important antiinflammatory derivative 2-(2-formylfurane)pyridylhydrazone 5p presented a 79% inhibition of pleurisy at a dose of 80.1 μmol/kg. We also described the results concerning the mechanism of action of this series of N-heterocyclic derivatives in platelet aggregation which suggest a Ca2+ participation, probably by a complexation scavenger mechanism. Compound 2-(2-formylfurane)pyridylhydrazone 5p was able to complex Ca2+ in in vitro experiments at 100 μM concentration, indicating that this series of compounds can act as Ca2+ scavenger depending on the nature of the aryl moiety present at the imine subunit.
- Todeschini, Adriane R.,De Miranda, Ana Luisa P.,Da Silva, Kelly Christine M.,Parrini, Sergio C.,Barreiro, Eliezer J.
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p. 189 - 199
(2007/10/03)
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- Fibrinogen receptor antagonists
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Compounds of the invention have the formula STR1 The compounds have fibrinogen receptor antagonist activity.
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- Chiral phosphorus(III) triflates. On the nature of the phosphorus-oxygen interaction
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Reaction of chiral phosphorodiamidites with trimethylsilyltriflate affords chiral phophorus(III) triflate species, such as 1-trifluoromethylsulfonato-2,9-(dibenzyl)diaza-1-phospha[4.0.3]bicyclononane 4, which has been examined by a combination of solution and solid state analytical techniques. Arguably the most important feature of this molecule is the nature of the interaction between phosphorus and triflate oxygen atoms. Single crystal X-ray diffraction analysis reveals that the phosphorus atom interacts principally with two oxygen atoms from two different triflate groups in the solid state, implying overall four-coordination at phosphorus. At distances of 2.841 and 2.755 A, these interactions are well within the van der Waals distance for a phosphorus-oxygen [P-O] interaction (ca. 3.35 A) but are nevertheless over 1 A longer than expected for a single [P-O] covalent bond. Investigations in solution via a combination of 31P, 19F, 13C, variable concentration, variable temperature NMR spectroscopy and solution conductivity provide support for a phosphorus-oxygen interaction which is intermediate between 'ionic' (two-coordinate phosphorus) and 'covalent' (three-coordinate phosphorus) and which possesses dynamic character in solution. Indeed, it has proved possible to calculate a relative equilibrium constant between 'ionic' and 'covalent' forms of 4 using empirical NMR data (13C and 19F; CH2Cl2 solvent; 300 K). These calculations return an equilibrium constant of ca. 3 (2.8 using 13C-NMR data and 3.3 using 19F-NMR data) in favour of the ionic form, a result commensurate with those suggested from variable temperature 19F-NMR and solution conductivity studies. Indeed, that the triflate group in 4 is capable of being displaced readily has been demonstrated by reaction with two-electron nitrogen, oxygen and phosphorus donor molecules. We have found 13C{1H}-NMR spectroscopy to be an extremely valuable probe of the ionic character of the triflate group in such systems providing a quantitative measure of the relative strength of interaction (relative basicity Br) between donor molecule and phosphorus atom of 4; the stronger the interaction, the more ionic the character of the triflate group and the lower the value of Br. Indeed, Br values for various ligands correlate well with steric and electronic properties of the latter and 31P-NMR resonances of the adducts themselves. As expected, the relative basicity of a given ligand correlates to the equilibrium constants K for adduct formation, which range from 39 M-1 for the weakest binding ligand studied (1,4-dioxane) to 5.4×104 M-1 for the strongest binding ligand (4-Me2N-NC5H4).
- Jones, Victoria A.,Sriprang, Sarin,Thornton-Pett, Mark,Kee, Terence P.
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p. 199 - 218
(2007/10/03)
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- Ligands containing alternating 2,6-linked pyridine and 2,5-linked thiophene units
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A variety of linear assemblies of alternating pyridine (2,6-linked) [P] and thiophene (2,5-linked) [T] units have been generated with up to seven units and their macrocyclisation investigated. The optimal methods involved the palladium(0) catalysed reaction of thienyl Grignard reagents with bromopyridines. In this way were made TPT, TPTPT, TPTPTPT, BrPTPBr and various XCH2PTPTPCH2X derivatives (X = H, Br, OH, OR and SBu-t). Alternative routes whereby pyridine units were 2,6-linked by CH2SCH2 units, with the intention of converting the bridge groups into thiophenes by a Hinsberg reaction, were also studied. The latter products {(HOCH2[P]CH2)2S and (HOCH2[P]-CH2SCH2)2[P]} proved to be highly effective ligands for transition metals, especially divalent ones such as Co2+, Ni2+ and Zn2+. No macrocyclisations were effective.
- Meth-Cohn, Otto,Jiang, Hui
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p. 3737 - 3745
(2007/10/03)
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- Aggregative activation in heterocyclic chemistry. Part 5. Lithiation of pyridine and quinoline with the complex base BuLi·Me2N(CH2)2OLi (BuLi·LiDMAE)
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It is shown that the complex base BuLi·LiDMAE reacts with pyridine to give metallated species which, after trapping by electrophiles, lead to 2-substituted pyridines in good to excellent yields. The same reactions have been less successfully performed with quinoline.
- Gros, Philippe,Fort, Yves,Caubere, Paul
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p. 3597 - 3600
(2007/10/03)
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- Novel base-initiated reactions of N-substituted pyridinium salts
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Reaction of N-fluoropyridinium triflate with a base in dichloromethane gave 2-chloropyridine as the major product along with 2-pyridyl triflate and 2-fluoropyridine, regardless of the nature of the base. This base-initiated reaction was also shown to take place similarly in other halogenated alkanes, ethers, a nitrile, aromatics, a ketone, vinyl ethers, alcohols and trimethylsilyl acetate as solvents to give pyridine derivatives substituted with a solvent molecule (s) at the 2-position. N-(Trifluoromethanesulfonyloxy)-and (benzenesulfonyloxy) pyridinium salts were found to undergo the same base-initiated reaction. These reactions may be explained by a postulated singlet carbene (canonical formula 11b) produced through proton abstraction of N-substituted pyridinium salts. A similar carbene reaction may thus likely occur in the thermal decomposition of thiatriazole 10. Ab initio MO calculations revealed the structure and properties of the labile deprotonated N-fluoropyridinium cation and supported the carbene intermediate reaction mechanism rather than a pyridynium or pyridyl cation mechanism. Quarroz's reports on the reactions of picolinic acid N-oxide and the reported reactions of pyridines with F2, CH3COOF or CsSO4F in solvents may be explained by this carbene mechanism.
- Umemoto, Teruo,Tomizawa, Ginjiro,Hachisuka, Hitoharu,Kitano, Masakatsu
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p. 161 - 168
(2007/10/03)
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- Antiinflammatory leukotriene B4 analogs
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This invention encompasses novel analogs of Leukotriene B4 which are selected from a compound of formula I, B--C~C--CH2 C(M2)--C~C--Y--C(M1)--A, or formula II, B--C~C--CH2 C(M2)--C~C--P--R5 --A: wherein Y is: STR1 wherein P is: STR2 Patentable intermediates, process for making the novel analogs and intermediates and preparation of useful pharmacological agents comprising the analogs and intermediates are part of this invention.
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- Utilizing Acetyl Hypofluorite for Chlorination, Bromination, and Etherification of the Pyridine System
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Acetyl hypofluorite, which is easily made from F2, possesses a strong electrophilic fluorine.This electrophile is able to attach itself to the nitrogen atom of pyridine and activate the ring toward nucleophilic attacks.The ultimate elimination of HF results in an overall easy nucleophilic displacement of the hydrogen of the important 2-position .The nucleophiles used: Clδ-, Brδ-, ROδ-, originate from solvents such as CH2Cl2, CH2Br2, and various primary alcohols.Thus, 2-halo- or 2-alkoxypyridines were formed.The reaction conditions (room temperature, very short reaction times, and good yields) transform the task of direct substitution of the pyridine ring from an extremely difficult to a very easy procedure.
- Hebel, David,Rozen, Shlomo
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p. 6298 - 6301
(2007/10/02)
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- REDUCTION OF N-OXIDE WITH BAKER'S YEAST
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Reduction of N-oxides with baker's yeast has been examined.In the reduction of acetylpyridine N-oxides, selective reduction takes place to give chiral pyridylethanol N-oxides.
- Takeshita, Mitsuhiro,Yoshida, Sachiko
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p. 871 - 874
(2007/10/02)
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- Preparation of biaryl compounds
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A method for the preparation of biaryl compounds is disclosed which comprises contacting an aromatic halide in the presence of a catalyst comprising zerovalent nickel, a bidentate phosphorus-containing coordinating ligand and a reducing metal in a polar, aprotic solvent system for a time and under conditions suitable for the formation of biaryl compound.
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- POTENTIOMETRIC STUDIES ON THE REACTION OF PICRIC ACID WITH SOME AROMATIC AMINES IN METHYL ISOBUTYL KETONE
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The reaction between picric acid and some aniline and pyridine derivatives has been investigated in methyl isobutyl ketone by the potentiometric method.Overall picrate formation constants KBHA, ammonium cationic acid dissociation constants KBH+ and apparent ion-pair formation Ki* and dissociation Kd* constants have been determined.
- Smagowski, Henryk,Bartnicka, Halina
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p. 201 - 209
(2007/10/02)
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- BASE-INITIATED REACTIONS OF N-FLUOROPYRIDINIUM SALTS; A NOVEL CYCLIC CARBENE PROPOSED AS A REACTIVE SPECIES
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A new type of base-initiated reactions of pyridinium salts was found and a novel cyclic carbene was proposed as the reactive species.
- Unemoto, Teruo,Tomizawa, Ginjiro
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p. 2705 - 2708
(2007/10/02)
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- ACTION DU N-BUTYLLITHIUM SUR LES BROMO-3 HALOGENO-2 PYRIDINES FLUOREE, CHLOREE ET BROMEE PRINCIPE ET ETUDE D'UNE POSSIBILITE REACTIONNELLE NOUVELLE: L'HOMOTRANSMETALLATION
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Apart from the common bromine-lithium exchange reaction in brominated aromatic compounds, it is possible to obtain a lithio-derivative quite different from the one usually described in such a reaction.This new reaction, which results from a special experimental condition is called 'homotransmetalation', and it occurs when using n-buthyllithium and 3-bromo 2-halogenopyridines (1).Different behaviour is observed with the three similar compounds (1:X = F,Cl,Br).Explanations are proposed of these results.It is then possible to compare the relative stabilities of the proposed lithio-structures.It is evident that nucleophilic substitution of bromine in position 4 of the pyridine ring is easier than is usually recognised.
- Mallet, M.,Queguiner, G.
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p. 3433 - 3440
(2007/10/02)
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- Nucleophilic Substitution of Halopyridines by Benzenethiolate Anion via a Radical Chain Mechanism
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2-Halopyridines 1a-d reacted with sodium thiophenoxide in DMF at 80 deg to afford the ipso-substitution products.The following relative order of reactivity was observed: 2-iodopyridine (1a) = 2-bromopyridine (1b) >> 2-chloropyridine (1c) = 2-fluoropyridine (1d).The reaction of 1b is inhibited by the electron scavenger azobenzene and by the radical scavenger benzoquinone.Furthermore, results of the reaction of 3-bromopyridine (2b) serve to rule out pyridyne mechanism.It is reasonable to suggest therefore that the reaction proceeds through the radical chain process containing one electron transfer, that is SRN1.
- Kondo, Shuji,Nakanishi, Minoru,Tsuda, Kazuichi
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p. 1243 - 1244
(2007/10/02)
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- Direct Conversion of Arylamines to the Halides by Deamination with Thionitrite or Related Compounds and Anhydrous Copper(II) Halides
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Reactions of various arylamines with either t-butyl thionitrite, t-butyl thionitrate, or p-toluenesulfonyl nitrite in the presence of anhydrous copper(II) halides under mild conditions gave corresponding aryl halides in good yields.This reaction in the presence of such olefins as acrylonitrile, styrene, and acrylic acid gave the corresponding 2-aryl-1-haloethanes as the main products. t-Butyl thionitrite, t-butyl thionitrate, and p-toluenesulfonyl nitrite were found to be better deaminative reagents than alkyl nitrites or alkyl nitrates due to their weak sulfur-nitrogen bonds.
- Oae, Shigeru,Shinhama, Koichi,Kim, Yong Hae
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p. 1065 - 1069
(2007/10/02)
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