573676-03-6Relevant articles and documents
Heterocyclic Allylsulfones as Latent Heteroaryl Nucleophiles in Palladium-Catalyzed Cross-Coupling Reactions
Markovic, Tim,Murray, Philip R.D.,Rocke, Benjamin N.,Shavnya, Andre,Blakemore, David C.,Willis, Michael C.
supporting information, p. 15916 - 15923 (2018/11/23)
Heterocyclic sulfinates are effective reagents in palladium-catalyzed coupling reactions with aryl and heteroaryl halides, often providing high yields of the targeted biaryl. However, the preparation and purification of complex heterocylic sulfinates can be problematic. In addition, sulfinate functionality is not tolerant of the majority of synthetic transformations, making these reagents unsuitable for multistep elaboration. Herein, we show that heterocyclic allylsulfones can function as latent sulfinate reagents and, when treated with a Pd(0) catalyst and an aryl halide, undergo deallylation, followed by efficient desulfinylative cross-coupling. A broad range of allyl heteroarylsulfones are conveniently prepared, using several complementary routes, and are shown to be effective coupling partners with a variety of aryl and heteroaryl halides. We demonstrate that the allylsulfone functional group can tolerate a range of standard synthetic transformations, including orthogonal C- and N-coupling reactions, allowing multistep elaboration. The allylsulfones are successfully coupled with a variety of medicinally relevant substrates, demonstrating their applicability in demanding cross-coupling transformations. In addition, pharmaceutical agents crizotinib and etoricoxib were prepared using allyl heteroaryl sulfone coupling partners, further demonstrating the utility of these new reagents.
Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides
Markovic, Tim,Rocke, Benjamin N.,Blakemore, David C.,Mascitti, Vincent,Willis, Michael C.
, p. 4437 - 4442 (2017/07/11)
Pyridine rings are ubiquitous in drug molecules; however, the pre-eminent reaction used to form carbon-carbon bonds in the pharmaceutical industry, the Suzuki-Miyaura cross-coupling reaction, often fails when applied to these structures. This phenomenon is most pronounced in 2-substituted pyridines, and results from the difficulty in preparing, the poor stability of, and low efficiency in reactions of pyridine-2-boronates. We demonstrate that by replacing these boronates with pyridine-2-sulfinates, a cross-coupling process of unrivalled scope and utility is realized. The corresponding 3-And 4-substituted pyridine variants are also efficient coupling partners. In addition, we apply these sulfinates in a library format to the preparation of medicinally relevant derivatives of the drugs varenicline (Chantix) and mepyramine (Anthisan).
Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions
Markovic, Tim,Rocke, Benjamin N.,Blakemore, David C.,Mascitti, Vincent,Willis, Michael C.
supporting information, p. 6033 - 6035 (2017/11/27)
A range of 5- and 6-membered heterocycle-derived sulfinates are shown to be effective nucleophilic coupling partners with aryl chlorides and bromides using Pd(0) catalysis. The use of optimal reaction conditions, specifically incorporating a P(t-Bu)2Me-derived Pd catalyst, allowed reactions to be performed at moderate temperatures and enabled the inclusion of a variety of sensitive functional groups. Challenging heterocyclic sulfinates, including pyrazine, pyridazine, pyrimidine, pyrazole, and imidazole, were all shown to perform well.
NOVEL METHOD OF PREPARING BENZOIMIDAZOLE DERIVATIVES
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Page/Page column 16, (2012/04/17)
This invention relates to a method of preparing a benzoimidazole derivative at high purity and high yield so as to enable the production of the benzoimidazole derivative compound as an antagonist against a vanilloid reactor-1, and particularly to a method
Discovery of novel 6,6-heterocycles as transient receptor potential vanilloid (TRPV1) antagonists
Blum, Charles A.,Caldwell, Timothy,Zheng, Xiaozhang,Bakthavatchalam, Rajagopal,Capitosti, Scott,Brielmann, Harry,De Lombaert, Stéphane,Kershaw, Mark T.,Matson, David,Krause, James E.,Cortright, Daniel,Crandall, Marci,Martin, William J.,Murphy, Beth Ann,Boyce, Susan,Jones, A. Brian,Mason, Glenn,Rycroft, Wayne,Perrett, Helen,Conley, Rachael,Burnaby-Davies, Nicola,Chenard, Bertrand L.,Hodgetts, Kevin J.
experimental part, p. 3330 - 3348 (2010/09/07)
The transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is a nonselective cation channel that can be activated by a wide range of noxious stimuli, including capsaicin, acid, and heat. Blockade of TRPV1 activation by selective antago
Aminoquinazolines as TRPV1 antagonists: Modulation of drug-like properties through the exploration of 2-position substitution
Blum, Charles A.,Zheng, Xiaozhang,Brielmann, Harry,Hodgetts, Kevin J.,Bakthavatchalam, Rajagopal,Chandrasekhar, Jayaraman,Krause, James E.,Cortright, Daniel,Matson, David,Crandall, Marci,Ngo, Chu K.,Fung, Lawrence,Day, Marta,Kershaw, Mark,De Lombaert, Stephane,Chenard, Bertrand L.
scheme or table, p. 4573 - 4577 (2009/04/06)
A focused SAR exploration of the lead 4-aminoquinazoline TRPV1 antagonist 2 led to the discovery of compound 18. In rats, compound 18 is readily absorbed following oral dosing and demonstrates excellent in vivo potency and efficacy in an acute inflammator
From arylureas to biarylamides to aminoquinazolines: Discovery of a novel, potent TRPV1 antagonist
Zheng, Xiaozhang,Hodgetts, Kevin J.,Brielmann, Harry,Hutchison, Alan,Burkamp, Frank,Brian Jones,Blurton, Peter,Clarkson, Robert,Chandrasekhar, Jayaraman,Bakthavatchalam, Rajagopal,De Lombaert, Stephane,Crandall, Marci,Cortright, Daniel,Blum, Charles A.
, p. 5217 - 5221 (2007/10/03)
Bioisosteric replacement of piperazine with an aryl ring in lead VR1 antagonist 1 led to the biarylamide series. The development of B-ring SAR led to the conformationally constrained analog 70. The resulting aminoquinazoline 70 represents a novel VR1 anta
SUBSTITUTED CINNOLIN-4-YLAMINES
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Page/Page column 37, (2008/06/13)
Substituted cinnolin-4-ylamines are provided, of the Formula (I): wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activityin vivo or in vitro, and are particularly useful in the treatmen
Substituted (7-pyridyl-4-phenylamino-quinazolin-2-yl)-methanol analogues
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Page/Page column 17, (2010/02/14)
Substituted (7-pyridyl-4-phenylamino-quinazolin-2-yl)-methanol analogues are provided. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions assoc
ARYL-SUBSTITUTED BENZO[D]ISOTHIAZOL-3-YLAMINE ANALOGUES
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Page/Page column 41, (2008/06/13)
Aryl-substituted benzo[d]isothiazol-3-ylamine analogues) are provided, of the Formula (I): wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro,and are particular
