- Synthesis of 2-Arylpiperidines via pd-catalyzed arylation of aza-Achmatowicz rearrangement products with arylboronic acids
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The first Pd-catalyzed arylation of aza-Achmatowicz rearrangement products with arylboronic acids is achieved, providing versatile 2-Aryldihydropyridinones for facile synthesis of highly functionalized 2-Arylpiperidines. Key to this arylation is the use of non-phosphine-ligand palladium precatalyst. The substrate scope is demonstrated with >26 examples, and the utility of 2-Aryldihydropyridinones is illustrated by the synthesis of a small collection of 2-Arylpiperidines with substituents or functional groups at any carbon (C2-C6) as well as two NK1 receptor antagonists (+)-CP-999,94 and (+)-L-733,060.
- Zhao, Guodong,Canterbury, Daniel P.,Taylor, Alexandria P.,Cheng, Xiayun,Mikochik, Peter,Bagley, Scott W.,Tong, Rongbiao
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p. 458 - 463
(2020/01/21)
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- 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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- Iridium-catalyzed selective hydrogenation of 3-hydroxypyridinium salts: A facile synthesis of piperidin-3-ones
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The selective hydrogenation of 3-hydroxypyridinium salts has been achieved using a homogeneous iridium catalyst, providing a direct access to 2- and 4-substituted piperidin-3-one derivatives with high yields, which are important organic synthetic intermediates and the prevalent structural motifs in pharmaceutical agents. Mild reaction conditions, high chemoselectivity, and easy scalability make this reaction highly practical for the synthesis of piperidin-3-ones.
- Huang, Wen-Xue,Wu, Bo,Gao, Xiang,Chen, Mu-Wang,Wang, Baomin,Zhou, Yong-Gui
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p. 1640 - 1643
(2015/04/14)
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- Electroreductive intramolecular coupling of aromatic β- and γ-imino esters: A new synthetic method for N-alkoxycarbonyl-2-aryl-3-ones and cis-2-aryl-3-ols of pyrrolidines and piperidines
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The electroreduction of aromatic β- and γ-imino esters prepared from β-alanine and GABA in the presence of chlorotrimethylsilane and subsequent N-alkoxycarbonylation of the resulting five- and six-membered cyclized amines gave mixed ketals of N-alkoxycarb
- Kise, Naoki,Ohya, Kengo,Arimoto, Kie,Yamashita, Yutaka,Hirano, Yuuki,Ono, Tadahiro,Ueda, Nasuo
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p. 7710 - 7719
(2007/10/03)
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- Use of NK-1 receptor antagonists for treating major depressive disorders
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The present invention provides methods for the treatment of major depressive disorders comprising oral administration of an orally active, long acting, CNS-penetrant NK-1 receptor antagonist and pharmaceutical compositions comprising such a NK-1 receptor
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- Use of NK-1 receptor antagonists for treating stress disorders
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The present invention provides the use of an orally active, long acting, CNS-penetrant NK-1 receptor antagonist for the manufacture of a medicament adapted for oral administration for the treatment or prevention of stress disorders without concomitant the
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- USE OF NK-1 RECEPTOR ANTAGONISTS FOR TREATING BIPOLAR DISORDERS
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The present invention provides methods for the treatment or prevention of bipolar disorder without concomitant therapy with other antidepressant or anti-anxiety agents which comprises oral administration of an orally active, long acting, CNS-penetrant NK-
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