- Direct Amidation of Esters by Ball Milling**
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The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram-scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent.
- Barreteau, Fabien,Battilocchio, Claudio,Browne, Duncan L.,Godineau, Edouard,Leitch, Jamie A.,Nicholson, William I.,Payne, Riley,Priestley, Ian
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supporting information
p. 21868 - 21874
(2021/09/02)
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- Palladium-Catalyzed Decarbonylative Iodination of Aryl Carboxylic Acids Enabled by Ligand-Assisted Halide Exchange
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We report an efficient and broadly applicable palladium-catalyzed iodination of inexpensive and abundant aryl and vinyl carboxylic acids via in situ activation to the acid chloride and formation of a phosphonium salt. The use of 1-iodobutane as iodide source in combination with a base and a deoxychlorinating reagent gives access to a wide range of aryl and vinyl iodides under Pd/Xantphos catalysis, including complex drug-like scaffolds. Stoichiometric experiments and kinetic analysis suggest a unique mechanism involving C?P reductive elimination to form the Xantphos phosphonium chloride, which subsequently initiates an unusual halogen exchange by outer sphere nucleophilic substitution.
- Boehm, Philip,Cacherat, Bastien,Lee, Yong Ho,Martini, Tristano,Morandi, Bill
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p. 17211 - 17217
(2021/07/02)
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- NaI-mediated oxidative amidation of benzyl alcohols/aromatic aldehydes to benzamides via electrochemical reaction
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In this research, we have developed a mild electrochemical process for oxidative amidation of benzyl alcohols/aromatic aldehydes with cyclic amines into the corresponding benzamides. This electroorganic synthetic method proceeds using NaI as a redox mediator under ambient temperature in undivided cell, providing more than 25 examples of amide products in moderate to good yields. The benefits of this reaction include one-pot synthesis, open air condition, proceed in aqueous media and no requirement of external conducting salt, base and oxidant.
- Rerkrachaneekorn, Tanawat,Tankam, Theeranon,Sukwattanasinitt, Mongkol,Wacharasindhu, Sumrit
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supporting information
(2021/04/15)
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- Copper-catalyzed and additive free decarboxylative trifluoromethylation of aromatic and heteroaromatic iodides
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A copper-catalyzed decarboxylative trifluoromethylation of (hetero)aromatic iodides has been developed. Importantly, this new copper-catalyzed reaction operates in the absence of any ligands and metal additives. The protocol shows good functional group tolerance and is compatible with heteroaromatic systems. The reaction proved scalable to a 15 mmol scale with increased yield. Finally, late-stage installation of the trifluoromethyl functionality afforded the N-trifluoroacetamide variant of the antidepressant agent, Prozac, demonstrating the applicability of the developed method.
- Johansen, Martin B.,Lindhardt, Anders T.
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p. 1417 - 1425
(2020/03/03)
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- A general electrochemical strategy for the Sandmeyer reaction
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Herein we report a general electrochemical strategy for the Sandmeyer reaction. Using electricity as the driving force, this protocol employs a simple and inexpensive halogen source, such as NBS, CBrCl3, CH2I2, CCl4, LiCl and NaBr for the halogenation of aryl diazonium salts. In addition, we found that these electrochemical reactions could be performed using anilines as the starting material in a one-pot fashion. Furthermore, the practicality of this process was demonstrated in the multigram scale synthesis of aryl halides using highly inexpensive graphite as the electrode. A series of detailed mechanism studies have been performed, including radical clock and radical scavenger study, cyclic voltammetry analysis and in situ electron paramagnetic resonance (EPR) analysis.
- Liu, Qianyi,Sun, Beiqi,Liu, Zheng,Kao, Yi,Dong, Bo-Wei,Jiang, Shang-Da,Li, Feng,Liu, Guoquan,Yang, Yang,Mo, Fanyang
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p. 8731 - 8737
(2018/12/10)
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- Palladium-Catalyzed Oxidative Carbonylation of Aryl Hydrazines with CO and O2 at Atmospheric Pressure
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Palladium-catalyzed aerobic oxidative aminocarbonylation and alkoxycarbonylation reactions with aryl hydrazines as coupling partners have been developed. The oxidative carbonylation of aryl hydrazines proceeded smoothly at atmospheric pressure CO, employi
- Tu, Yongliang,Yuan, Lin,Wang, Tao,Wang, Changliu,Ke, Jiamei,Zhao, Junfeng
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p. 4970 - 4976
(2017/05/12)
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- Copper-catalyzed and iodide-promoted aerobic C-C bond cleavage/C-N bond formation toward the synthesis of amides
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A copper-catalyzed and iodide-promoted aerobic C-C bond cleavage/C-N bond formation reaction between ketone and simple amine was developed toward the synthesis of amides, which are useful synthetic intermediates in organic synthesis and important skeletons of biologically active molecules. Notably, the reaction conditions are very mild, and preliminary mechanistic investigations indicate that molecular oxygen might be involved in the C-C bond cleavage process.
- Wu, Kun,Huang, Zhiliang,Ma, Yiyang,Lei, Aiwen
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p. 24349 - 24352
(2016/03/15)
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- Direct oxidative amidation between methylarenes and amines in water
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An environmentally friendly direct oxidative amidation between methylarenes and free amines was developed. The aromatic amide could be prepared efficiently from raw chemicals by employing TBHP as a "green" oxidant with co-catalysis of TBAI and FeCl3 in water.
- Wang, Tao,Yuan, Lin,Zhao, Zhenguang,Shao, Ailong,Gao, Meng,Huang, Yangfei,Xiong, Fei,Zhang, Huali,Zhao, Junfeng
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supporting information
p. 2741 - 2744
(2015/05/27)
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- N2 extrusion and co insertion: A novel palladium-catalyzed carbonylative transformation of aryltriazenes
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A novel procedure for the replacement of N2 with CO of aryltriazenes has been developed. Aryltriazenes were converted to the corresponding arylamides catalyzed by 1 mol % of PdCl2/P(o-Tol)3 under CO pressure. In this process, aryldiazonium salts were generated in the presence of 40 mol % of MeSO3H. Nitrogen was released from the substrates and CO formally inserted. Aryl bromides, iodides, alkynes, and free hydroxyl groups can be tolerated in this transformation.
- Li, Wanfang,Wu, Xiao-Feng
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p. 1910 - 1913
(2015/04/27)
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- Ring-opening metathesis polymerization-based recyclable magnetic acylation reagents
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An operationally simple method for the acylation of amines utilizing carbon-coated metal nanoparticles as recyclable supports is reported. Highly magnetic carbon-coated cobalt (Co/C) and iron (Fe/C) nanobeads were functionalized with a norbornene tag (Nb-tag) through a "click" reaction followed by surface activation employing Grubbs-II catalyst and subsequent grafting of acylated N-hydroxysuccinimide ROMPgels (ROMP= ring-opening metathesis polymerization). The high loading (up to 2.6 mmolg -1) hybrid material was applied in the acylation of various primary and secondary amines. The products were isolated in high yields (86-99%) and excellent purities (all >95% by NMR spectroscopy) after rapid magnetic decantation and simple evaporation of the solvents. The spent resins were successfully re-acylated by acid chlorides, anhydrides, and carboxylic acids and reused for up to five consecutive cycles without considerable loss of activity.
- Kainz, Quirin M.,Linhardt, Roland,Maity, Pradip K.,Hanson, Paul R.,Reiser, Oliver
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p. 721 - 729
(2013/07/27)
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- Integration of lead optimization with crystallography for a membrane-bound ion channel target: Discovery of a new class of AMPA receptor positive allosteric modulators
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A novel series of AMPAR positive modulators is described that were identified by high throughput screening. The molecules of the series have been optimized from a high quality starting point hit to afford excellent developability, tolerability, and effica
- Ward, Simon E.,Harries, Mark,Aldegheri, Laura,Austin, Nigel E.,Ballantine, Stuart,Ballini, Elisa,Bradley, Daniel M.,Bax, Benjamin D.,Clarke, Brian P.,Harris, Andrew J.,Harrison, Stephen A.,Melarange, Rosemary A.,Mookherjee, Claudette,Mosley, Julie,Dal Negro, Gianni,Oliosi, Beatrice,Smith, Kathrine J.,Thewlis, Kevin M.,Woollard, Patrick M.,Yusaf, Shahnaz P.
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experimental part
p. 78 - 94
(2011/03/19)
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- Nickel-catalyzed C-H arylation of azoles with haloarenes: Scope, mechanism, and applications to the synthesis of bioactive molecules
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Novel nickel-based catalytic systems for the C-H arylation of azoles with haloarenes and aryl triflates have been developed. We have established that Ni(OAc)2/bipy/LiOtBu serves as a general catalytic system for the coupling with aryl bromides and iodides as aryl electrophiles. For couplings with more challenging electrophiles, such as aryl chlorides and triflates, the Ni(OAc)2/dppf (dppf=1,1′-bis(diphenylphosphino)ferrocene) system was found to be effective. Thiazoles, benzothiazoles, oxazoles, benzoxazoles, and benzimidazoles can be used as the heteroarene coupling partner. Upon further investigation, we discovered a new protocol for the present coupling using Mg(OtBu)2 as a milder and less expensive alternative to LiOtBu. Attempts to reveal the mechanism of this nickel-catalyzed heterobiaryl coupling are also described. This newly developed methodology has been successfully applied to the syntheses of febuxostat (a xanthine oxidase inhibitor that is effective for the treatment of gout and hyperuricemia), tafamidis (effective for the treatment of TTR amyloid polyneuropathy), and texaline (a natural product having antitubercular activity). Copyright
- Yamamoto, Takuya,Muto, Kei,Komiyama, Masato,Canivet, Jerome,Yamaguchi, Junichiro,Itami, Kenichiro
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supporting information; experimental part
p. 10113 - 10122
(2011/10/08)
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- CARBAZOLE AND CARBOLINE KINASE INHIBITORS
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The present invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) compounds inhibit tyrosine kinase activity of Jak2, thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.
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Page/Page column 172
(2010/08/04)
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- MORPHOLINONE COMPOUNDS AS FACTOR IXA INHIBITORS
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The present invention provides a compound of Formula (I) as described herein, or a pharmaceutically acceptable salt or a solvate thereof. The present invention also provides pharmaceutical compositions comprising one or more said compounds, and methods fo
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Page/Page column 316
(2010/06/20)
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- COMPOUNDS WHICH POTENTIATE AMPA RECEPTOR AND USES THEREOF IN MEDICINE
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Compounds of formula (I) and salts and solvates are provided: formula (I). Processes for preparation, pharmaceutical compositions, and uses thereof as a medicament, for example in the treatment of a disease or condition mediated by a reduction or imbalance in glutamate receptor function, such as schizophrenia or cognition impairment, are also disclosed.
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Page/Page column 92-93
(2008/06/13)
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- New phenylpyridylpiperazine compounds
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A compound selected from those of formula (I): [image] wherein: X represents a C(O) or SO2 group, R1 represents an aryl group or a group NR3R4 wherein R3 and R4 are as defined in the description, R2 represents an alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl-(C1-C6)alkyl group, its isomers, and addition salts thereof, and medicinal products containing the same which are useful in treating conditions treatable by antagonists of type H3 central histamine receptors.
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Page/Page column 15
(2008/06/13)
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- Benzodioxepine derivatives
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This invention relates to compounds of the formula wherein B, X, Y, Z, R1 and R2 are as defined in the description, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are modulated by ACCβ inhibitors.
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Page/Page column 13
(2010/02/11)
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- BENZO [b][1,4] DIOXEPINE DERIVATIVES
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This invention relates to compounds of the formula (I), wherein B, X, Y, Z, R1 and R2 are as defined in the description, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are modulated by ACCβ inhibitors.
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Page/Page column 28
(2010/02/11)
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- Amides useful as brain imaging agents
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Certain radioiodine containing amides useful as brain imaging agents are disclosed. The compounds of the subject invention are represented by the formula STR1 wherein I is a radioisotope of iodine with I-123 being preferred, R1 and R2 are the same or different and are selected from the grooup consisting of hydrogen, hydroxy, alkyl, aryl, substituted aryl, aralkyl, anilino and carbamoylmethyl or R1 and R2 taken together with the nitrogen to which they are attached form a 5- or 6-membered ring.
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