- The methoxyallene approach to oxacycles, part 2: Stereoselective synthesis of 2,3-disubstituted oxepanes
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2,3-Disubstituted oxepanes 3 and 4 were stereoselectively synthesized from methoxyallene (1) and iodide 2. The trans stereochemistry of diol 3 was established by NMR studies of the bicyclic precursor 10, while the cis stereochemistry of 4 was secured by using the highly diastereoselective reducing agent L-Selectride. Georg Thieme Verlag Stuttgart.
- Perez, Manuel,Canoa, Pilar,Gomez, Generosa,Teijeira, Marta,Fall, Yagamare
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Read Online
- Methoxyallene, a building block for the synthesis of seven-membered oxacycles
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An efficient new approach for the synthesis of seven-membered oxacycles is described.
- Fall, Yagamare,Gomez, Generosa,Fernandez, Carlos
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Read Online
- PYRIMIDINE-FUSED CYCLIC COMPOUND, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
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Disclosed in the present disclosure are a pyrimidine-fused cyclic compound or a pharmaceutically acceptable salt, hydrate, prodrug, stereoisomer, solvate or isotope labeled compound thereof. Also provided in the present disclosure are a preparation method for the compound, a composition comprising the compound and a use of the compound for the preparation of a medicament for the prevention and/or treatment of a disease or condition associated with abnormal SHP2 activity.
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Paragraph 0363-0365
(2021/02/26)
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- Design of a mesoscale continuous-flow route toward lithiated methoxyallene
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The unique nucleophilic properties of lithiated methoxyallene allow for C C bond formation with a wide variety of electro-philes, thus introducing an allenic group for further functionali-zation. This approach has yielded a tremendously broad range of (hetero)cyclic scaffolds, including precursors to active pharmaceutical ingredients. To date, however, its valorization at scale is hampered by the batch synthesis procedure, which suf- fers from serious safety issues. Hence, the attractive heat-and mass-transfer properties of flow technology were exploited to establish a mesoscale continuous-flow route toward lithiated methoxyallene. An excellent conversion of 94 % was obtained, corresponding to a methoxyallene throughput of 8.2 g h1. The process is characterized by short reaction times, mild reaction conditions and a stoichiometric use of reagents.
- Seghers, Sofie,Heugebaert, Thomas S. A.,Moens, Matthias,Sonck, Jolien,Thybaut, Joris W.,Stevens, Christian V.
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- Synthesis of polyfunctional triethoxysilanes by 'click silylation'
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The copper-catalyzed 'click silylation' has been exploited for the chemical modification of γ-azidopropyltriethoxysilane (AzPTES) with a wide range of terminal alkynes (1a-1v) in a one-pot operation. The novel 1,2,3-triazole-triethoxysilane derivatives (2a-2v) were synthesized by this procedure and comprehensively characterized by IR spectra, 1H and 13C NMR, and HRMS studies.
- Singh, Gurjaspreet,Mangat, Satinderpal Singh,Singh, Jandeep,Arora, Aanchal,Sharma, Ramesh K.
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supporting information
p. 903 - 909
(2015/03/03)
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- NOVEL PYRROLIDINE DERIVED BETA 3 ADRENERGIC RECEPTOR AGONISTS
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The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of β3-adrenoceptor.
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Page/Page column 57
(2015/04/22)
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- Synthesis of polyfunctional triethoxysilanes by 'click silylation'
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The copper-catalyzed 'click silylation' has been exploited for the chemical modification of γ-azidopropyltriethoxysilane (AzPTES) with a wide range of terminal alkynes (1a-1v) in a one-pot operation. The novel 1,2,3-triazole-triethoxysilane derivatives (2a-2v) were synthesized by this procedure and comprehensively characterized by IR spectra, 1H and 13C NMR, and HRMS studies.
- Singh, Gurjaspreet,Mangat, Satinderpal Singh,Singh, Jandeep,Arora, Aanchal,Sharma, Ramesh K.
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p. 903 - 909
(2014/02/14)
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- COMPOUNDS AND ANTI-TUMOR NQO1 SUBSTRATES
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Compounds of Formula (I) can be selectively lethal toward a variety of different cancer cell types. The compounds are useful for the management, treatment, control, or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy.
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Page/Page column 86
(2013/04/25)
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- Pendant triazole ring assisted mesogen containing side chain liquid crystalline polymethacrylates: Synthesis and characterization
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Two series of click chemistry assisted alkoxymethyl-1H-[1,2,3]-triazol-1-yl containing sidechain liquid-crystalline polymethacrylates were synthesized by free radical polymerization technique. Mesogen was linked to backbone through various spacer units. Monomers and polymers were characterized by FT-IR, 1H and 13C-NMR spectral techniques. Thermal stability of polymers was confirmed by thermogravimetric analysis. Mesomorphic property and phase transition temperature of polymers were analysed by differential scanning calorimetry and polarized optical microscopy. Phase transition temperature and mesomorphic property of polymers with respect to insertion of polar alkoxy group on terminal triazole ring and spacer length between backbone and mesogen were investigated. Polymers exhibited grainy like textures under polarized optical microscopy. Spacer length between mesogen and backbone alters phase transition temperature of the polymers. Indian Academy of Sciences.
- Palani,Saravanan,Kannan
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scheme or table
p. 81 - 89
(2012/02/01)
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- Direct, catalytic synthesis of carbapenams via cycloaddition/rearrangement cascade reaction: Unexpected acetylenes' structure effect
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Reactions of acetylenes derived from glyceraldehyde and propargyl aldehyde show remarkable reactivity in Kinugasa cycloaddition/rearrangement cascade process catalyzed by Cu(I) ion. Reactions proceed by formation of a rigid dinuclear copper(I) complex in which each copper ion is coordinated to one or both oxygen atoms in the acetylene molecule and to both triple bonds. It has been demonstrated that one oxygen atom can be replaced by the phenyl ring, which is able to coordinate the copper ion by the aromatic sextet. Kinugasa reactions that proceed in a high yield can also be performed in the presence of a catalytic amount of the copper salt to provide products in an acceptable yield without a decrease of diastereoselectivity.
- Mames, Adam,Stecko, Sebastian,Mikolajczyk, Paulina,Soluch, Magdalena,Furman, Bartlomiej,Chmielewski, Marek
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supporting information; experimental part
p. 7580 - 7587
(2011/03/17)
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- Fluorine-substituted azobenzene destabilizes polar form of optically switchable fulgimide unit in copolymer system
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Fulgimide and various size and electronic nature of substituents on the terminal position of azobenzene in the pendant homo/copolymethacrylates were synthesized. Differential scanning calorimetry analysis indicates the homopolymer possessing C-form fulgimide unit exhibited higher Tm than that of E-form of the homopolymer and revealed C-form is highly ordered. Thermal stability suggests azobenzene homopolymers with electron donating substituents have high thermal stability than electron withdrawing substituents. Polarized optical microscopy observation disclosed homopolymers viz., NI, CY, FL, ME, and T-ME exhibited liquid crystalline mesophases between their Tm and Ti. Optical properties of homo/copolymers were investigated by UV-vis and fluorescence spectroscopy. UV-vis spectroscopy displayed C-form fulgimide absorption in F-co-FL around 482 nm which is around 40 nm lesser than C-form of substituted azobenzene copolymers. Similarly, fluorescence pattern of F-co-FL by UV irradiation exhibited emission intensity slowly increased to certain level then decreases with two new emissions at 430 and 480 nm attributed to terminal position of fluorine atom on azobenzene destabilizes polar form (C-form) fulgimide unit in the copolymer.
- Chinnusamy, Saravanan,Palaninathan, Kannan
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scheme or table
p. 1565 - 1578
(2011/02/26)
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- Synthesis and characterization of [1,2,3]-triazole containing liquid crystals through click reaction
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Two series of heterocyclic liquid crystalline compounds with [1,2,3]-triazole ring at the terminal position were synthesized and analyzed for mesomorphic properties and its characteristics. Heterocyclic triazole core was introduced in to the target compound through click reaction between aromatic phenolic azide and alkyl propargyl ethers. The structure of the target compounds and intermediates was conformed by the 1H NMR, 13C NMR and IR spectral techniques. All the compounds in both the series were exhibited thermotropic liquid crystalline mesophase. These compounds show enantiotropic Smectic A phase on heating and cooling experiments. This was further confirmed using differential scanning calorimetric investigations. Interestingly, earlier reports on non-polar alkyl group attached to [1,2,3]-triazole heterocyclic ring was not showing any liquid crystalline properties but in the present investigation introduction of polar alkoxy group very near to [1,2,3]-triazole heterocyclic ring displayed liquid crystalline properties.
- Srividhya,Manjunathan,Thirumaran,Saravanan,Senthil
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experimental part
p. 7 - 13
(2009/09/30)
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- 6-Substituted-4-(3-bromophenylamino)quinazolines as putative irreversible inhibitors of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases with enhanced antitumor activity
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A series of new 6-substituted-4-(3-bromophenylamino)quinazoline derivatives that may function as irreversible inhibitors of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases have been prepared. These inhibitors have, at the C-6 position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These compounds were prepared by acylation of 6-amino-4-(3-bromophenylamino)quinazoline with unsaturated acid chlorides or mixed anhydrides. We show that attaching a basic functional group onto the Michael acceptor results in greater reactivity, due to intramolecular catalysis of the Michael addition and/or an inductive effect of the protonated basic group. This, along with improved water solubility, results in compounds with enhanced biological properties. We present molecular modeling and experimental evidence that these inhibitors interact covalently with the target enzymes. One compound, 16a, was shown to have excellent oral activity in a human epidermoid carcinoma (A431) xenograft model in nude mice.
- Tsou,Mamuya,Johnson,Reich,Gruber,Ye,Nilakantan,Shen,Discafani,DeBlanc,Davis,Koehn,Greenberger,Wang,Wissner
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p. 2719 - 2734
(2007/10/03)
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- Solvent and substituent effects on conjugated eliminations in propargylic systems
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The deprotonation of 4-methoxy-but-2-ynal diethyl acetal by n- butyllithium induces an acetylenic-allenic isomerization (in diethylether) or a conjugated elimination reaction (in THF), providing the corresponding 1,4- dialkoxycumulene. An allenyllithium, that has been trapped as an allenylstannane, is proposed to be a common intermediate to both pathways. Also, the deprotonation of 4-dialkylamino-but-2-ynal diethyl acetals in the same conditions affords a mixture of (E) and (Z) aminocrotonates of which formation can be explained by a chemioselective removal of the acetalic proton leading to an intermediate allenyllithium that has equally been trapped by stannylation. (C) 2000 Elsevier Science Ltd.
- Le Strat, Frédéric,Maddaluno, Jacques
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p. 5367 - 5371
(2007/10/03)
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- Hydrolysis and Alcoholysis of Esters of o-Nitrobenzenesulfonic Acid
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The rate of solvolysis of esters of o-nitrobenzenesulfonic acid with water and C1-C4 alcohols is satisfactorily described by two-parametric Hammett-Taft equation with predominating effect of the electronic factor σ*. The effect of the structure of the hydrocarbon rest in the sulfonic ester group does not fit to this relationship.
- Sendega,Makitra,Pirig
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p. 1438 - 1446
(2007/10/03)
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- Oligosaccharide analogues of polysaccharides. Part 5. Studies on the cross-coupling of alkynes and haloalkynes
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The cross-coupling of the homopropargylic ether 1 and the halopropargylic ethers 2a and 2b was optimized, and aspects of the coupling mechanism were studied. Coupling promoted by Pd0 and Cu1 in the presence of an amine yielded a mixture of the heterodimer 3 and the homodimers 4 and 5. Optimizations were first directed at suppressing homo-coupling. Homo-coupling is partially due to a H/I exchange (1 + 2A ? 6 + 7) promoted by CuI and an amine. The exchange, but not the formation of homodimers, was largely suppressed in DMSO. The influence of phosphine ligands was also evaluated. Weaker σ-donors (with the exception of PPh3) lead to a faster coupling and to a higher ratio of hetero- to homodimers, with P(fur)3 leading to the cleanest reaction. Homodimers are also formed (together with I2·((i-Pr)2NH) by reductive dimerization of the iodoalkyne 2a in the presence of [Pd2(dba)3], CuI, and (i-Pr)2NH. Bulky and acceptor-substituted amines reduced the extent of the dimerization of 2a, but the bulkiest amines did not promote coupling. Better results were obtained by using the bromoalkyne 2b. Neither dimerization of 2b, nor H/Br exchange between 1 and 2b were observed. Coupling of 1 and 2b was slower than the one of 1 and 2a, but gave higher yields of the heterodimer 3. The yield of 3 and the ratio of hetero- to homodimers was greatly improved by addition of LiI; no phosphine ligand is then required. While the oxidative addition of the iodoalkyne 2a to [Pd(PPh3)4] (2a→8a) was rapid, the one of the bromoalkyne 2b was much slower and proceeded via the η2-complex 9 as evidenced by 1H-NMR spectroscopy. The rearrangement of 9 to the bromopalladium σ-complex 8b follows first-order kinetics (k = 0.014 min-1). CuBr greatly increased the rate of this rearrangement. LiI caused rapid substitution of Br by I in the Pd σ-complex (8b→8a), but not in 9, nor in 2b. The σ-complex 8a did not react with the alkyne 1 in the presence of (i-Pr)2NH, unless Cu(I) was added. The alkynes 10 or 1 did not react with CuI and either TMEDA or (i-Pr)2NH to yield detectable amounts of the Cu-acetylides 11 or 12.
- Cai,Vasella
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p. 2053 - 2064
(2007/10/03)
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- Catecholborane reductive cleavage of allyl and propargyl acetals and ketals: A simple route to allyl and prop-2-ynyl ethers
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The chemoselective conversion of allyl and prop-2-ynyl acetals as well as ketals by reductive cleavage with catecholborane into the corresponding allyl and prop-2-ynyl ethers is described.
- Bovicelli,Mincione,Patamia
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p. 907 - 913
(2007/10/02)
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- CHEMISTRY OF SYSTEMS OF THE ALLYL TYPE I. SYNTHESIS OF ALLYL AND 2-PROPYNYL ETHERS UNDER PHASE-TRANSFER CATALYSIS CONDITIONS
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A convenient method was developed for the synthesis of allyl and 2-propynyl ethers under phase-transfer catalysis conditions, which make it possible to dispense with the use of an inert organic solvent and to ensure the practically complete conversion of the alkylating agent.
- Ibragimov, I. I.,Tarasov, V. A.,Aliev, A. G.,Belyaeva, V. I.
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p. 1398 - 1402
(2007/10/02)
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- 1-heterocyclic bicyclo-octanes
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Pesticidal bicyclo-octanes are of the formula STR1 where R is a substituted or unsubstituted aliphatic or aromatic group, R' and R3 are H or a substituted or unsubstituted aliphatic or aromatic group, R2 is a substituted or unsubstituted heterocyclic group containing at least one ring nitrogen and is preferably a 3- or 4- pyridyl group, Z is CH2 CH2, CH2 O--CH2 S or COCH2 or CH(OR5)CH2 where R5 is H, alkyl, acyl or carbamoyl at Y and Y' are O or S(O)m where m is 0, 1 or 2. Various methods for their preparation are described.
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- The Stereochemistry of Organometallic Compounds. XXX. Hydrocyanation of Alkynol Ethers: a New Stereospecific Route to α-Alkylidene γ-Lactones
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The regioselectivity of hydrocyanation of a range of protected α- and β-hydroxyalkynes has been investigated and shown to by highly susceptible to steric effects.Some of the products from hydrocyanation of protected β-hydroxyalkynes have been converted into α-alkylidene γ-lactones.
- Jackson, W. Roy,Perlmutter, Patrick,Smallridge, Andrew J.
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p. 251 - 261
(2007/10/02)
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- MEDICINAL PLANTS OF SOUTHERN AFRICA. PART 2. SYNTHESIS OF 1,3-BIS-(4-METHOXYPHENYL)PENTA-1,4-DIENE, A STEREOISOMER OF DIMETHYLHINOKIRESINOL, AND ITS 4-MONOMETHOXY ANALOGUE
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A six-step synthesis of the title compounds (6) and (7) from prop-2-yn-1-ol, and proceeding via 3-(4-methoxyphenyl)prop-1-yne, is described.Detailed 1H n.m.r. spectral analysis (500 MHz) suggests that the synthetic compounds have a 1,2-E stereochemistry in contrast to the Z-configuration present in the naturally occurring hinokiresinol (3).By utilizing a different, and much less efficient route, a small quantity of (Z)-3-(4-methoxyphenyl)-1-phenylpenta-1,4-diene (5) was obtained.
- Ameer, Farouk,Drewes, Siegfried E.,Drewes, Mark W.,Roos, Gregory H. P.,Watson, Martin C.
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p. 1425 - 1430
(2007/10/02)
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- Metabolic depropargylation and its relationship to aldehyde dehydrogenase inhibition in vivo
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The relationship between metabolic depropargylation in vitro to inhibition of the low K(m) aldehyde dehydrogenase (AIDH) of rat liver mitochondria in vivo was determined for a number of compounds bearing a propargyl substituent on nitrogen or oxygen. Only those compounds which enzymatically released the highly reactive α, β-acetylenic aldehyde, propiolaldehyde, when incubated in vitro with phenobarbital-induced rat liver microsomes, e.g., tripropargylamine (4), pargyline (1a), and N-propargylbenzylamine (1b), significantly elevated blood acetaldehyde levels when administered in vivo. Mitochondrial AlDH activity in these animals was corresponding reduced to ≤20% that of control animals. Compounds that did not inhibit mitochondrial AlDH activity to this degree did not produce significant levels of propiolaldehyde when incubated with microsomes. Thus, for this series of compounds, metabolic depropargylation is a requirement for AlDH inhibitory activity in vivo.
- Shirota,DeMaster,Elberling,Nagasawa
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p. 669 - 673
(2007/10/02)
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