- Nickel-catalyzed reductive monofluoroakylation of alkyl tosylate with bromofluoromethane to primary alkyl fluoride
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A nickel-catalysed direct terminal monofluoromethlyation between alkyl tosylates and a low-cost, industrial raw material bromofluoromethane has been developed. This transformation has demonstrated high efficiency, mild conditions, and good functional-grou
- Cui, Ru,Hu, Duo-Duo,Sheng, Jie,Wang, Xi-Sheng,Wu, Bing-Bing,Zheng, Hong-Qian
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supporting information
p. 9084 - 9087
(2021/09/14)
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- BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY
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The present invention relates to compounds useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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Paragraph 0287-0291
(2020/08/28)
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- Erbium-Catalyzed Regioselective Isomerization-Cobalt-Catalyzed Transfer Hydrogenation Sequence for the Synthesis of Anti-Markovnikov Alcohols from Epoxides under Mild Conditions
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Herein, we report an efficient isomerization-transfer hydrogenation reaction sequence based on a cobalt pincer catalyst (1 mol %), which allows the synthesis of a series of anti-Markovnikov alcohols from terminal and internal epoxides under mild reaction conditions (≤55 °C, 8 h) at low catalyst loading. The reaction proceeds by Lewis acid (3 mol % Er(OTf)3)-catalyzed epoxide isomerization and subsequent cobalt-catalyzed transfer hydrogenation using ammonia borane as the hydrogen source. The general applicability of this methodology is highlighted by the synthesis of 43 alcohols from epoxides. A variety of terminal (23 examples) and 1,2-disubstituted internal epoxides (14 examples) bearing different functional groups are converted to the desired anti-Markovnikov alcohols in excellent selectivity and yields of up to 98%. For selected examples, it is shown that the reaction can be performed on a preparative scale up to 50 mmol. Notably, the isomerization step proceeds via the most stable carbocation. Thus, the regiochemistry is controlled by stereoelectronic effects. As a result, in some cases, rearrangement of the carbon framework is observed when tri-and tetra-substituted epoxides (6 examples) are converted. A variety of functional groups are tolerated under the reaction conditions even though aldehydes and ketones are also reduced to the respective alcohols under the reaction conditions. Mechanistic studies and control experiments were used to investigate the role of the Lewis acid in the reaction. Besides acting as the catalyst for the epoxide isomerization, the Lewis acid was found to facilitate the dehydrogenation of the hydrogen donor, which enhances the rate of the transfer hydrogenation step. These experiments additionally indicate the direct transfer of hydrogen from the amine borane in the reduction step.
- Liu, Xin,Longwitz, Lars,Spiegelberg, Brian,T?njes, Jan,Beweries, Torsten,Werner, Thomas
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p. 13659 - 13667
(2020/11/30)
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- Regioselective Sulfonylation/Acylation of Carbohydrates Catalyzed by FeCl3 Combined with Benzoyltrifluoroacetone and Its Mechanism Study
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A catalytic amount of FeCl3 combined with benzoyl trifluoroacetone (Hbtfa) (FeCl3/Hbtfa = 1/2) was used to catalyze sulfonylation/acylation of diols and polyols using diisopropylethylamine (DIPEA) or potassium carbonate (K2CO3) as a base. The catalytic system exhibited high catalytic activity, leading to excellent isolated yields of sulfonylation/acylation products with high regioselectivities. Mechanism studies indicated that FeCl3 initially formed [Fe(btfa)3] (btfa = benzoyl trifluoroacetonate) with twice the amount of Hbtfa under basic conditions in the solvent acetonitrile at room temperature. Then, Fe(btfa)3 and two hydroxyl groups of the substrates formed a five- or six-membered ring intermediate in the presence of the base. The subsequent reaction between the cyclic intermediate and a sulfonylation reagent led to the selective sulfonylation of the substrate. All key intermediates were captured in the high-resolution mass spectrometry assay, therefore demonstrating this mechanism for the first time.
- Dong, Hai,Liu, Yu,Lv, Jian,Zhu, Jia-Jia
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p. 3307 - 3319
(2020/03/25)
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- The synthesis of precursor of FP- (+) DTBZ
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A synthetic route to the precursor of FP- (+) DTBZ was disclosed, in which 3-hydroxy-4-methoxybenzaldehyde was employed as a starting material. In the method, the benzyl-protecting protocol and the in-situ Diels-Alder reaction made the procedure more practical because of the mild conditions for selectively deprotection and the accelerated reaction process.
- Wu, Caijiao,Li, Hui,Sun, Feiyang,Bao, Changshun,Bao, Xuefei,Chen, Guoliang
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p. 3218 - 3225
(2019/09/13)
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- COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ENHANCER OF ZESTE HOMOLOG 2 POLYPEPTIDE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 1106
(2018/07/15)
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- Mivacurium chloride intermediate and method for synthesizing Mivacurium Chloride using mivacurium chloride intermediate
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The invention belongs to the technical field of synthesis of pharmaceutical compounds, and particularly discloses an improved Mivacurium Chloride intermediate suitable for industrial production and amethod for synthesizing Mivacurium Chloride using the mi
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Paragraph 0048; 0049; 0050
(2018/09/29)
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- A Library of Fluorinated Electrophiles for Chemical Tagging and Materials Synthesis
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Various applications could benefit from new fluorinated molecules that offer chemical handles for quickly functionalizing reactive surfaces and molecules. Herein, we report the synthesis of a library of fluorinated molecules that contain nonafluoro-tert-butyl groups and electrophilic handles, mostly acrylates and acrylamides. Featuring a variety of hydrophobic and hydrophilic linkers, these molecules could find use in polymer chemistry, biomaterials, biomedical imaging, and protein tagging.
- Kasper, Jonathan J.,Hitro, Jamie E.,Fitzgerald, Sabrina R.,Schnitter, Joseph M.,Rutowski, James J.,Heck, John A.,Steinbacher, Jeremy L.
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p. 8095 - 8103
(2016/10/03)
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- Synthesis and Characterization of Constitutionally Isomeric Oriented Calix[6]arene-Based Rotaxanes
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Oriented rotaxanes composed of tris(N-phenylureido)calix[6]arene wheel 1 and N,N′-dialkyl viologen-based axles were synthesized in which the span between the diphenylacetyl stoppers at the wheel upper and lower rim and the bis-pyridinium cation portion of
- Zanichelli, Valeria,Ragazzon, Giulio,Arduini, Arturo,Credi, Alberto,Franchi, Paola,Orlandini, Guido,Venturi, Margherita,Lucarini, Marco,Secchi, Andrea,Silvi, Serena
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p. 1033 - 1042
(2016/03/01)
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- Novel fluoroalkyl derivatives of selective kappa opioid receptor antagonist JDTic: Design, synthesis, pharmacology and molecular modeling studies
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Novel N-and O-fluoroalkyl derivatives of the highly potent KOR antagonist JDTic were designed and synthesized. Their opioid receptor properties were compared in both in vitro binding assays and modeling approach. All compounds displayed nanomolar affiniti
- Schmitt, Sébastien,Colloc'H, Nathalie,Perrio, Cécile
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p. 742 - 750
(2015/04/14)
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- Novel fluoroalkyl derivatives of selective kappa opioid receptor antagonist JDTic: Design, synthesis, pharmacology and molecular modeling studies
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Novel N- and O-fluoroalkyl derivatives of the highly potent KOR antagonist JDTic were designed and synthesized. Their opioid receptor properties were compared in both in vitro binding assays and modeling approach. All compounds displayed nanomolar affinit
- Schmitt, Sbastien,Colloc'h, Nathalie,Perrio, Ccile
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p. 742 - 750
(2015/02/19)
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- Design, synthesis, and structure-affinity relationships of regioisomeric N-benzyl alkyl ether piperazine derivatives as σ-1 receptor ligands
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A series of N-(benzofuran-2-ylmethyl)-N′-benzylpiperazines bearing alkyl or fluoroalkyl aryl ethers were synthesized and evaluated at various central nervous system receptors. Examination of in vitro σ1 {[3H](+)-pentazocine} and σ2 ([3H]DTG) receptor binding profiles of piperazines 11-13 and 25-36 revealed several highly potent and σ1 selective ligands, notably, N-(benzofuran-2- ylmethyl)-N′-(4′-methoxybenzyl)piperazine (13, Ki = 2.7 nM, σ2/σ1 = 38) and N-(benzofuran-2-ylmethyl)- N′-(4′-(2″-fluoroethoxy)benzyl)piperazine (30, Ki = 2.6 nM, σ2/σ1 = 187). Structural features for optimal σ1 receptor affinity and selectivity over the σ2 receptor were identified. On the basis of its favorable log D value, 13 was selected as a candidate for the development of a σ1 receptor positron emission tomography radiotracer. [ 11C]13 showed high uptake in the brain and other σ receptor-rich organs of a Papio hamadryas baboon. The in vivo evaluation of [11C]13 indicates that this radiotracer is a suitable candidate for imaging the σ1 receptor in neurodegenerative processes.
- Moussa, Iman A.,Banister, Samuel D.,Beinat, Corinne,Giboureau, Nicolas,Reynolds, Aaron J.,Kassiou, Michael
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experimental part
p. 6228 - 6239
(2010/11/02)
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- Tandem alkylation - Michael addition to vinylogous carbonates for the stereoselective construction of 2,3,3,6-tetrasubstituted tetrahydropyrans
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A stereoselective method for the synthesis of substituted tetrahydropyran derivatives employing a tandem SN2-Michael addition sequence to vinylogous carbonates is developed. The method is extended to the synthesis of bicyclic ether motifs present in polyether ladder toxins.
- Gharpure, Santosh J.,Reddy, S. Raja Bhushan
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supporting information; scheme or table
p. 2519 - 2522
(2009/10/18)
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- NOVEL COMPOUND HAVING AFFINITY FOR AMYLOID
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A compound that has affinity with amyloid, exhibits sufficiently rapid clearance from normal tissues, and is suppressed in toxicity such as mutagenicity is provided, which is represented by the following formula (1): or a salt thereof, wherein R1 is a group selected from hydrogen, hydroxyl group, carboxyl group, sulfate group, amino group, nitro group, cyano group, an alkyl substituent with one to 4 carbon atoms or an alkoxy substituent with one to 4 carbon atoms; R2 is a radioactive halogen substituent; and m is an integer of 0 to 2, and a low-toxic diagnostic agent for Alzheimer's disease comprising a compound represented by the above formula or a salt thereof is also provided.
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Page/Page column 2; 15; 24
(2009/04/23)
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- SULFAMOYL-CONTAINING DERIVATIVES AND USES THEREOF
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Sulfamoyl-containing compounds are disclosed, having utility as inhibitors of disease-related targets, such as Heat Shock Protein 90 (HSP90), and which are useful for treating disorders, e.g., proliferative disorders, including HSP90-mediated disorders. Methods for preparing and using the disclosed compounds are also described.
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Page/Page column 21
(2008/06/13)
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- Silver(I) oxide mediated highly selective monotosylation of symmetrical diols. Application to the synthesis of polysubstituted cyclic ethers
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(Matrix Presented) The reaction of symmetrical diols and oligo(ethylene glycol)s with a stoichiometric amount of p-toluenesulfonyl chloride in the presence of silver(I) oxide and a catalytic amount of potassium iodide led selectively to the monotosylate derivatives in high yields. Polysubstituted cyclic ethers were obtained readily upon treatment of the corresponding diols with an excess of silver oxide. The high selectivity was explained on the basis of the difference in acidity between the two hydroxy groups, which undergo an intramolecular hydrogen bonding.
- Bouzide, Abderrahim,Sauve, Gilles
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p. 2329 - 2332
(2007/10/03)
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- Synthesis, modification, and characterization of a family of homologues of exo-calix[4]arene: exo-[n.m.n.m]Metacyclophanes, n,m ≥ 3
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A general strategy for the preparation of the family of exo-[n.m.n.m]metacyclophanes (n,m ≥ 3) in 6-steps (starting from 2-bromoanisole)that utilizes a [2 + 2] approach to furnish the exometacyclophane ring in good to moderate yield is described. The soluble copper catalyst [CuBr- LiSPh-LiBr-THF] is used to efficiently couple Grignard and alkyl or ether tosylate reagents in several of the synthetic steps, including the ring construction in the final step. The exo-[n.m.n.m]- metacyclophane ring is conformationally mobile on the NMR time scale, and X-ray crystallography reveals that exo-[3.3.3.3]metacyclophane 2a assumes a cone conformation, and that exo-[6.6.6.6]- metacyclophane 6a assumes a chair conformation. Molecular mechanics calculations show that both conformations for each exo-metacyclophane are very similar in energy. Regiocontrol over the alkylation and acylation of the phenolic oxygens of 2b is problematic, although the preparation of the tetraacetylated 18 and alkylation of 2b with CH2BrCl to furnish the methylene-linked mono- and bis-adducts 19 and 20 are straightforward.
- Burns, Dennis H.,Chan, Ho-Kit,Miller, Jeffrey D.,Jayne, Charles L.,Eichhorn, David M.
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p. 5185 - 5196
(2007/10/03)
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- Quaternary Salts of 2-imidazole. 5. Structure-Activity Relationships for Side-Chain Nitro-, Sulfone-, Amino-, and Aminosulfonyl-Substituted Analogues for Therapy against Anticholinesterase Intoxication
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Several quaternary imidazolium oxime derivatives incorporating side chains bearing nitro, sulfone, amino, and aminosulfonyl substituents were prepared and evaluated as treatment therapeutics for anti-AChE intoxication.In vivo test results in the mouse rev
- Koolpe, Gary A.,Lovejoy, Steven M.,Goff, Dane A.,Lin, Kuei-Ying,Leung, Doris S.,et al.
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p. 1368 - 1376
(2007/10/02)
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- SYNTHESIS OF MACROCYCLIC ACETALS CONTAINING LIPOPHILIC SUBSTITUENTS
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A series of new mecrocyclic acetals all containing lipophilic substituents were prepared by reacting the appropriate diols and lipophilic acetal-containing dichlorides or ditosylates.The reactions using the ditosylates gave the best yields.Several of the macrocycles contained pyridine subcyclic units.The lipophilic acetals were obtained by reacting a chain aldehyde with 2-hydroxyethyl chloride or tosylate and 3-hydroxypropyl chloride od tosylate.At least two of the new pydridino ligands complexed with metal ions as shown by the use of these materials as carriers for silver nitrate through a water-methylene chloride-water bulk liquid membrane system.
- Bradshaw, Jerald S.,Krakowiak, Krzysztof E.,LindH, Gypzy C.,Izatt, Reed M.
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p. 4271 - 4276
(2007/10/02)
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- 2-(acetoacetyloxy)-3-(octadecyloxy)propyl-3-trimethylammoniopropyl phosphate or a pharmaceutically acceptable salt thereof
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A compound provided by the present invention, of the formula STR1 wherein R1 is C14-20 alkyl; R2, R3 and R4 are independently hydrogen or C1-5 alkyl, or STR2 represents a cyclic ammonio gro
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