- A new and high yielding synthesis of unstable pyrroles via a modified Clauson-Kaas reaction
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An investigation of the reaction requirements to effect the Clauson-Kaas pyrrole synthesis led to the formulation of a new procedure that avoids the contact of pyrroles to heat or strongly acidic conditions that cause decomposition of the desired products. The procedure involves mild hydrolysis of 2,5-dimethoxytetrahydrofuran in water to the activated species 2,5-dihydroxytetrahydrofuran that reacts with primary amines in an acetate buffer at room temperature to give N-substituted pyrroles in high yield. In the case of chiral amines, pyrrole formation proceeds with no detectable epimerisation. Acid- or heat-sensitive pyrroles are also obtained in high yield and purity.
- Gourlay, Brendon S.,Molesworth, Peter P.,Ryan, John H.,Smith, Jason A.
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- A synthetic protocol for (?)-ketorolac; development of asymmetric gold(I)-catalyzed cyclization of allyl alcohol with pyrrole ring core
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An asymmetric synthesis of (?)- and (+)-ketorolac was achieved with 89% ee using a novel Friedel–Crafts (FC) type C–C bond forming cyclization of an allyl alcohol containing a pyrrole ring core in the presence of a bimetallic gold(I) salt complex prepared from a 2:2:1 combination of AuCl·SMe2, AgOTf and chiral Quinaphos.
- Sasaki, Ikuo,Yamasaki, Naoto,Kasai, Yusuke,Imagawa, Hiroshi,Yamamoto, Hirofumi
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- Catalytic Hydrogenation of N-protected α-Amino Acids Using Ruthenium Complexes with Monodentate Phosphine Ligands
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A ruthenium complex with a monodentate phosphine ligand was used to catalytically hydrogenate N-protected α-amino acids under essential retention of the configuration of their α-chiral centers. Among the ligands tested for this hydrogenation, which proceeds at a relatively low temperature, tris(para-fluorophenyl)phosphine exhibited the best performance. In comparison, electron-rich monodentate, bidentate, and tridentate phosphines were far less effective. The precatalyst Ru(OAc)2[(p-FC6H4)3P]2 was synthesized and isolated, and its structure was determined by a single-crystal X-ray diffraction analysis. N-protected α-amino acids with neutral alkyl side chains, including polar functional groups such as sulfides, indoles, ethers, phenols, pyrroles, and arenes, are compatible with the applied hydrogenation conditions, affording the corresponding optically active 2-substituted-2-(1H-pyrrol-1-yl)ethan-1-ol (2-amino ethanol) derivatives in moderate to high yield. (Figure presented.).
- Saito, Akari,Yoshioka, Shota,Naruto, Masayuki,Saito, Susumu
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p. 424 - 429
(2019/11/28)
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- Discovery of bioavailable 4,4-disubstituted piperidines as potent ligands of the chemokine receptor 5 and inhibitors of the human immunodeficiency virus-1
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We describe robust chemical approaches toward putative CCR5 scaffolds designed in our laboratories. Evaluation of analogues in the 125I-[MIP-1β] binding and Ba-L-HOS antiviral assays resulted in the discovery of 64 and 68 in the 4,4-disubstitited piperidine class H, both potent CCR5 ligands (pIC50 = 8.30 and 9.00, respectively) and HIV-1 inhibitors (pIC50 = 7.80 and 7.84, respectively, in Ba-L-HOS assay). In addition, 64 and 68 were bioavailable in rodents, establishing them as lead molecules for further optimization toward CCR5 clinical candidates.
- Kazmierski, Wieslaw M.,Aquino, Christopher,Chauder, Brian A.,Deanda, Felix,Ferris, Robert,Jones-Hertzog, Deborah K.,Kenakin, Terrence,Koble, Cecilia S.,Watson, Christian,Wheelan, Pat,Yang, Hanbiao,Youngman, Michael
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experimental part
p. 6538 - 6546
(2009/11/30)
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- 5-HT4 receptor agonist compounds
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The invention provides novel quinolinone-carboxamide 5-HT4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds.
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Page/Page column 20
(2008/06/13)
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