- Palladium-Catalyzed Synthesis of α-Carbonyl-α′-(hetero)aryl Sulfoxonium Ylides: Scope and Insight into the Mechanism
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Despite recent advances, a general method for the synthesis of α-carbonyl-α′-(hetero)aryl sulfoxonium ylides is needed to benefit more greatly from the potential safety advantages offered by these compounds over the parent diazo compounds. Herein, we report the palladium-catalyzed cross-coupling of aryl bromides and triflates with α-carbonyl sulfoxonium ylides. We also report the use of this method for the modification of an active pharmaceutical ingredient and for the synthesis of a key precursor of antagonists of the neurokinin-1 receptor. In addition, the mechanism of the reaction was inferred from several observations. Thus, the oxidative addition complex [(XPhos)PhPdBr] and its dimer were observed by 31P{1H} NMR, and these complexes were shown to be catalytically and kinetically competent. Moreover, a complex resulting from the transmetalation of [(XPhos)ArPdBr] (Ar = p-CF3-C6H4) with a model sulfoxonium ylide was observed by mass spectrometry. Finally, the partial rate law suggests that the transmetalation and the subsequent deprotonation are rate-determining in the catalytic cycle.
- Janot, Christopher,Chagnoleau, Jean-Baptiste,Halcovitch, Nathan R.,Muir, James,A?ssa, Christophe
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p. 1126 - 1137
(2019/12/30)
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- Anti-inflammatory effects of two new methyl and morpholine derivatives of diphenhydramine on rats
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Diphenhydramines are one of the first-generation histamine H1-receptor antagonists of the ethanolamine class that demonstrate many pharmacological properties including anti-inflammatory effects. In this research, bromo (II) and two new tolyl derivatives of I, (Di [p-tolyl] [dimethylaminoethoxy] methane, III) and (Di [p-tolyl] [2-morpholinoethoxy] methane, IV) were synthesized. Their acute and chronic anti-inflammatory activities were evaluated with the formalin and histamine-induced rat paw edema. The vascular permeability in formalin and histamine-induced paw edema, in xylene-induced ear edema, and in peritonitis after acetic acid application into peritoneal cavity were also measured and compared to II. Cotton pellet-induced granuloma model was selected for inducing chronic inflammations in rats. The newly synthesized analogs of diphenhydramine seemed effective to decrease acute inflammations. It was concluded that the prominent anti-phlogistic effects of the new drugs could be related to its reduction vascular permeability mechanism(s) or to its antagonistic effects on H1 histamine receptors. Springer Science+Business Media, LLC 2011.
- Ahmadi, Abbas,Khalili, Mohsen,Hajikhani, Ramin,Safari, Narjes,Nahri-Niknafs, Babak
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p. 3532 - 3540
(2013/02/25)
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