- High-Throughput Screening of Reductive Amination Reactions Using Desorption Electrospray Ionization Mass Spectrometry
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This study describes the latest generation of a high-throughput screening system that is capable of screening thousands of organic reactions in a single day. This system combines a liquid handling robot with desorption electrospray ionization (DESI) mass spectrometry (MS) for a rapid reaction mixture preparation, accelerated synthesis, and automated MS analysis. A total of 3840 unique reductive amination reactions were screened to demonstrate the throughputs that are capable with the system. Products, byproducts, and intermediates were all monitored in full-scan mass spectra, generating a complete view of the reaction progress. Tandem mass spectrometry experiments were conducted to verify the identity of the products formed. The amine and electrophile reactivity trends represented in the data match what is expected from theory, indicating that the system accurately models the reaction performance. The DESI results correlated well with those generated using more traditional mass spectrometry techniques like liquid chromatography-mass spectrometry, validating the data generated by the system.
- Cooks, R. Graham,Ferreira, Christina R.,Li, Yangjie,Logsdon, David L.,Paschoal Sobreira, Tiago Jose,Thompson, David H.
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supporting information
p. 1647 - 1657
(2020/10/26)
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- Metal-Organic Capsules with NADH Mimics as Switchable Selectivity Regulators for Photocatalytic Transfer Hydrogenation
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Switchable selective hydrogenation among the groups in multifunctional compounds is challenging because selective hydrogenation is of great interest in the synthesis of fine chemicals and pharmaceuticals as a result of the importance of key intermediates. Herein, we report a new approach to highly selectively (>99%) reducing C=X (X = O, N) over the thermodynamically more favorable nitro groups locating the substrate in a metal-organic capsule containing NADH active sites. Within the capsule, the NADH active sites reduce the double bonds via a typical 2e- hydride transfer hydrogenation, and the formed excited-state NAD+ mimics oxidize the reductant via two consecutive 1e- processes to regenerate the NADH active sites under illumination. Outside the capsule, nitro groups are highly selectively reduced through a typical 1e- hydrogenation. By combining photoinduced 1e- transfer regeneration outside the cage, both 1e- and 2e- hydrogenation can be switched controllably by varying the concentrations of the substrates and the redox potential of electron donors. This promising alternative approach, which could proceed under mild reaction conditions and use easy-to-handle hydrogen donors with enhanced high selectivity toward different groups, is based on the localization and differentiation of the 2e- and 1e- hydrogenation pathways inside and outside the capsules, provides a deep comprehension of photocatalytic microscopic reaction processes, and will allow the design and optimization of catalysts. We demonstrate the advantage of this method over typical hydrogenation that involves specific activation via well-modified catalytic sites and present results on the high, well-controlled, and switchable selectivity for the hydrogenation of a variety of substituted and bifunctional aldehydes, ketones, and imines.
- Wei, Jianwei,Zhao, Liang,He, Cheng,Zheng, Sijia,Reek, Joost N. H.,Duan, Chunying
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p. 12707 - 12716
(2019/09/04)
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- Rapid and efficient access to secondary arylmethylamines
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Ammoniomethyl trifluoroborates are very powerful reagents that can be used to access biologically relevant aryl- and heteroaryl-methylamine motifs via Suzuki-Miyaura cross-couplings. Until now, this method was limited to the production of tertiary and primary amines. The synthesis of a large array of secondary ammoniomethyltrifluoroborates has been achieved through a one step nucleophilic substitution reaction on the potassium bromomethyltrifluoroborate. Smooth cross-coupling conditions have been designed, based on the use of an aminobiphenyl palladium precatalyst, to couple these trifluoroborates efficiently with aryl bromides. This strategy offers a new way to access biologically relevant motifs and allows, with the previously developed methods, access to all three classes of aminomethylarenes. Secondary ammoniomethyltrifluoroborates can be easily synthesized by nucleophilic substitution on potassium bromomethyltrifluoroborate. These reagents have then been used in Suzuki-Miyaura cross-couplings with aryl bromides, offering an effective access to the aminomethylarene structural motif. This new method provides an interesting alternative to the reductive amination procedure (see scheme). Copyright
- Fleury-Brégeot, Nicolas,Raushel, Jessica,Sandrock, Deidre L.,Dreher, Spencer D.,Molander, Gary A.
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p. 9564 - 9570
(2012/08/28)
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- Controlled and chemoselective reduction of secondary amides
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This communication describes a metal-free methodology involving an efficient and controlled reduction of secondary amides to imines, aldehydes, and amines in good to excellent yields under ambient pressure and temperature. The process includes a chemoselective activation of a secondary amide with triflic anhydride in the presence of 2-fluoropyridine. The electrophilic activated amide can then be reduced to the corresponding iminium using triethylsilane, a cheap, rather inert, and commercially available reagent. Imines can be isolated after a basic workup or readily transformed to the aldehydes following an acidic workup. The amine moiety can be accessed via a sequential reductive amination by the addition of silane and Hantzsch ester hydride in a one-pot reaction. Moreover, this reduction tolerates various functional groups that are usually reactive under reductive conditions and is very selective to secondary amides.
- Pelletier, Guillaume,Bechara, William S.,Charette, Andre B.
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supporting information; experimental part
p. 12817 - 12819
(2010/11/05)
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- Potent and selective CC-chemokine receptor-2 (CCR2) antagonists as a potential treatment for asthma
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A number of compounds bearing a quaternary ammonium moiety were found to be antagonists with nanomolar binding affinity for the chemokine receptor-2. The structure-activity relationships in the series are described herein along with some detailed characte
- Lagu, Bharat,Gerchak, Chrissy,Pan, Meng,Hou, Cuifen,Singer, Monica,Malaviya, Ravi,Matheis, Michele,Olini, Gil,Cavender, Druie,Wachter, Michael
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p. 4382 - 4386
(2008/02/09)
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- QUATERNARY SALT CCR2 ANTAGONISTS
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Quaternary salt compounds of Formula (I) or pharmaceutically acceptable forms thereof, which are CCR2 antagonists and are useful in preventing, treating or ameliorating CCR2 mediated inflammatory syndromes, disorders or diseases in a subject in need thereof.
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Page/Page column 65-67; 72-74
(2008/06/13)
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- Quaternary salt CCR2 antagonists
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Quaternary salt compounds of Formula (I) or pharmaceutically acceptable forms thereof, which are CCR2 antagonists and are useful in preventing, treating or ameliorating CCR2 mediated inflammatory syndromes, disorders or diseases in a subject in need thereof.
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Page/Page column 74; 80
(2008/06/13)
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- Substituted indolines which inhibit receptor tyrosine kinases
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Indolinones of the formula having an inhibitory effect on receptor tyrosine kinases and cyclin/CDK complexes, as well as on the proliferation of endothelial cells and various tumor cells. Exemplary are: (a) 3-Z-[1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone, (b) 3-Z-[(1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone, and (c) 3-Z-[1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-metboxycarbonyl-2-indolinone.
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Page column 42
(2008/06/13)
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- Substituted indolinones with kinase inhibitory activity
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Substituted indolinones of general formula having effect on various kinases and cycline/CDK complexes and on the proliferation of various tumour cells. Exemplary compounds are: 3-Z-[1-(4-(N-Benzyl-N-methyl-aminomethyl)-phenylamino)-1-methyl-methylene]-5-a
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- Indolinones having kinase inhibitory activity
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The present invention relates to substituted indolinones of general formula [Figure] wherein R1 to R5, and X are defined as in claim 1, the isomers thereof and the salts thereof, particularly the physiologically acceptable salts thereof which have valuable pharmacological properties, particularly an inhibitory effect on various kinases and cycline/CDK complexes and on the proliferation of various tumour cells, pharmaceutical compositions containing these (compounds, their use and processes for preparing them.
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- Effect of the temperature on the stoichiometry of borane dimethyl sulfide reduction of secondary and tertiary amides
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A simple procedure has been described for the reduction of secondary and tertiary amides to amines using borane-dimethyl sulfide in theoretical amounts.
- Bonnat,Hercouet,Le Corre
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p. 1579 - 1582
(2007/10/02)
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- NAD(P)H MODELS-XVII. -- METAL ION CATALYZED REDUCTION OF IMINES BY 3,5-DIETHOXYCARBONYL-2,6-DIMETHYL-1,4-DIHYDROPYRIDINE (HANTZSCH ESTER)
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The reduction of imines by 3,5-diethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine, an NAD(P)H model, is catalyzed by Mg(2+) ions.Kinetic measurements of the reduction of a series of imines derived from substituted benzaldehydes, show a very small polar sub
- Steevens, J. B.,Pandit, U. K.
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p. 1395 - 1400
(2007/10/02)
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