123206-83-7Relevant academic research and scientific papers
Highly Diastereoselective Synthesis of Medium-Sized Carbocycle-Fused Piperidines via Sequential Hydride Shift Triggered Double C(sp3)-H Bond Functionalization
Kataoka, Miyabi,Otawa, Yuna,Ido, Natsuki,Mori, Keiji
, p. 9334 - 9338 (2019/11/19)
Herein we report a diastereoselective synthesis of medium-sized carbocycle-fused piperidines via [1,n (n = 6, 7)]-[1,5]-sequential hydride shift triggered double C(sp3)-H bond functionalization. When cinnamylidene malonates having N,N-dibenzyl propylamine moiety were treated with 5 mol % of Yb(OTf)3, a [1,6]-[1,5]-sequential hydride shift/cyclization process proceeded to afford seven-membered carbocycle-fused piperidines with excellent diastereoselectivities. This sequential system was applicable to the synthesis of eight-membered carbocycle-fused piperidines by an unprecedented [1,7]-[1,5]-sequential hydride shift/cyclization process.
Construction of seven-and eight-membered carbocycles by Lewis acid catalyzed C(sp3)-H bond functionalization
Otawa, Yuna,Mori, Keiji
supporting information, p. 13856 - 13859 (2019/11/21)
We achieved a concise construction of seven-and eight-membered carbocycles via Lewis acid catalyzed C(sp3)-H bond functionalization. In these reactions, a quite rare [1,6 (or 7)]-hydride shift/cyclization process proceeded smoothly to afford seven-and eight-membered carbocycles with good chemical yields starting from substrates with high conformational freedom.
1,3,8-TRIAZASPIRO[4,5]DECAN-4-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ORL-1 RECEPTOR MEDIATED DISORDERS
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Paragraph 0241-0242, (2017/02/28)
The present invention is directed to novel 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formulawherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, substance abuse, neuropathic pain, acute pain, migraine, asthma, cough and for improved cognition.
Characterization of the Dynamic Equilibrium between Closed and Open Forms of the Benzoxaborole Pharmacophore
Vshyvenko, Sergey,Clapson, Marissa L.,Suzuki, Itaru,Hall, Dennis G.
supporting information, p. 1097 - 1101 (2016/12/18)
Benzoxaboroles are a class of five-membered hemiboronic acids that recently attracted significant attention as a new pharmacophore on account of their unique structural and physicochemical properties and their ability to interact selectively with biomolecules. Their structural behavior in water and its effect on their physiological properties remain unclear, especially the question of dynamic hydrolytic equilibrium of the oxaborole ring. Herein, we used NMR spectroscopy, in mixed aqueous-organic solvent, to confirm the strong preference for the closed form of benzoxaborole and its six- and seven-membered homologues over the open boronic acid form. Only with the eight-membered homologue does the cyclic form become unfavorable. Using dynamic VT-NMR studies with designed probe compound 20, we demonstrate that the oxaborole ring undergoes rapid hydrolytic ring closing-opening at ambient temperature at a rate of >100 Hz via a mechanism featuring rate-limiting proton-transfer steps. This knowledge can help provide a better understanding of the behavior of benzoxaboroles in biological systems.
Effect of chain length on radical to carbanion cyclo-coupling of bromoaryl alkyl-linked oxazolines: 1,3-Areneotropic migration of oxazolines
Marshall, Laura J.,Roydhouse, Mark D.,Slawin, Alexandra M. Z.,Walton, John C.
, p. 898 - 911 (2007/10/03)
(Chemical Equation Presented) 2-Halophenylalkyl-2-oxazolines with alkyl chain spacers of two to six C atoms (n = 0-4) were prepared and their S RN1-type reactions with several base systems examined. The best conditions to promote cyclocoupling to the corresponding benzocycloalkane derivatives involved use of LDA in THF. The precursors with 3-C-atom and 4-C-atom spacers gave good yields of 2-(1′-phenylindan-1′-yl)-2- oxazolines and 2-(1-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)-2-oxazoline, respectively. The major products from the precursor with a 5-C-atom spacer were derivatives of benzocycloheptane in which the oxazoline group had undergone a novel areneotropic migration from the end of the spacer to the benzo ring. The product from reaction of the corresponding 2-C-atom precursor was a 9-oxazolinophenanthrene derivative. EPR spectroscopy showed the intermediates of the LDA-promoted reactions to be radical anions of the product benzocycloalkanes. This supported an SRN1-type chain mechanism involving initial production of aryl radicals connected to azaenolate ions via the spacer groups. Intramolecular radical to carbanion coupling then generated ring-closed benzocycloalkane radical anions that transferred an electron to more precursor. Diastereoselective radical to carbanion cyclo-coupling reactions were carried out with 2-bromophenylpropyl precursors containing chiral 2-oxazolines. The diastereoselectivity achievable was modest, but the product diastereoisomeric Indane derivatives were easily separable by chromatography.
Novel ligands for the human histamine H1 receptor: Synthesis, pharmacology, and comparative molecular field analysis studies of 2-dimethylamino-5-(6)-phenyl-1,2,3,4-tetrahydronaphthalenes
Ghoneim, Ola M.,Legere, Jacqueline A.,Golbraikh, Alexander,Tropsha, Alexander,Booth, Raymond G.
, p. 6640 - 6658 (2007/10/03)
This paper reports the synthesis of a novel series of (±)-2-dimethylamino- 5- and 6-phenyl-1,2,3,4-tetrahydronaphthalene derivatives (5- and 6-APTs), and, corresponding affinity, functional activity, and, molecular modeling studies with regard to drug des
Synthesis of precursors for medium-ring aromatic lactones
Metay, Estelle,Leonel, Eric,Sulpice-Gaillet, Christine,Nedelec, Jean-Yves
, p. 1682 - 1688 (2007/10/03)
Hydroxyacids have been prepared via the nickel-catalysed electrochemical arylation of ethyl acrylate from an ortho-substituted aryl bromide. Protection and deprotection steps have been selected in terms of suitability and efficiency. The lactonisation was
1,3,8-Triazaspiro[4.5]decan-4-one derivatives useful for the treatment of ORL-1 receptor mediated disorders
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, (2008/06/13)
The present invention is directed to novel 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formula wherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, substance abuse, neuropathic pain, acute pain, migraine, asthma, cough and for improved cognition.
Palladium-catalyzed intramolecular C-O bond formation
Kuwabe,Torraca,Buchwald
, p. 12202 - 12206 (2007/10/03)
A number of oxygen heterocycles were synthesized using the palladium-catalyzed intramolecular etherification of aryl halides by employing di-tert-butylphosphinobiaryl ligands. The reaction proceeds under mild conditions using weak bases such as Cs2CO3 or K3PO4. A variety of functional groups are tolerated in the reaction, and enantioenriched alcohols can be coupled without erosion of optical purity. The mildness of the reaction conditions allows for the use of polyfunctionalized substrates. This method was used as the key step in the synthesis of MKC-242, an antidepressant currently in clinical trials. The synthesis of MKC-242 was achieved in 40% overall yield from commercially available sesamol and acrylonitrile.
