- Preparation of novel pyridine-fused tris-heterocycles; pyrido[4,3-e]pyrrolo-/pyrido[4,3-e]furano[2,3-c]pyridazines and pyrido[3,4-b]pyrrolo[3,2-d]pyrrole
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Three novel pyrido-fused tris-heterocycles have been prepared based on a Suzuki coupling and subsequent cyclisation approach. Pyrido[4,3-e]pyrrolo[2,3-c]pyridazine (3b, 77%) and pyrido[4,3-e]furano[2,3-c]pyridazine (5b, 76%) were obtained by intramolecular diazocoupling. Successful diazocoupling of furan (5b) is thus reported for the first time by NOBF4 generation of the diazonium intermediate. N-TIPS-pyrido[3,4-b]pyrrolo[3,2-d]pyrrole (TIPS-4b) was synthesised by thermal cyclisation of pyridyl nitrene in considerably higher yield (71%) than previously experienced from similar cyclisations, due to TIPS-activation.
- Stockmann, Vegar,Eriksen, Kristine L.,Fiksdahl, Anne
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Read Online
- Pyochelin Biosynthetic Metabolites Bind Iron and Promote Growth in Pseudomonads Demonstrating Siderophore-like Activity
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Pseudomonads employ several strategies to sequester iron vital for their survival including the use of siderophores such as pyoverdine and pyochelin. Similar in structure but significantly less studied are pyochelin biosynthetic byproducts, dihydroaeruginoic acid, aeruginoic acid, aeruginaldehyde (IQS), and aeruginol, along with two other structurally related molecules, aerugine and pyonitrins A-D, which have all been isolated from numerous Pseudomonad extracts. Because of the analogous substructure of these compounds to pyochelin, we hypothesized that they may play a role in iron homeostasis or have a biological effect on other bacterial species. Herein, we discuss the physiochemical evaluation of these molecules and disclose, for the first time, their ability to bind iron and promote growth in Pseudomonads.
- Kaplan, Anna R.,Musaev, Djamaladdin G.,Wuest, William M.
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p. 544 - 551
(2021/03/03)
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- BENZOTHIAZOL COMPOUNDS AND METHODS USING THE SAME FOR TREATING NEURODEGENERATIVE DISORDERS
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The present disclosure provides a compound of general Formula (I) having c-abl kinase inhibitory activity or pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the compound, and a method useful to treat or prevent neurodegenerative diseases using the compound.
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Paragraph 0521; 0524; 0525
(2019/04/18)
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- Alkylammoniotrifluoroborate functionalized polystyrenes: Polymeric pre-catalysts for the metal-free borylation of heteroarenes
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Three polymeric versions of ansa-N,N-dialkylammoniumtrifluoroborate ambiphilic molecules based on the styrene motif (poly(1-NMe2H+-2-BF3--4-styrene) (P-Me), poly(1-NEt2H+-2-BF3--4-styrene) (P-Et) and poly(1-piperidinyl-H+-2-BF3--4-styrene) (P-Pip)) were synthesized, characterized and tested as heterogeneous pre-catalysts for the borylation of electron-rich heteroarenes. These heterogeneous versions of previously reported pre-catalysts show similar reactivity patterns and represent the first examples of solid-supported FLP metal-free catalysts for the C-H borylation of heteroarenes.
- Bouchard, Nicolas,Fontaine, Frédéric-Georges
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supporting information
p. 4846 - 4856
(2019/04/17)
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- NOVEL NICOTINAMIDE DERIVATIVES OR SALTS THEREOF
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An object of the present invention is to provide to a compound and a pharmaceutical composition, which have excellent Syk-inhibitory activity. Th e present invention provides a nicotinamide derivative represented by the follo wing formula (I) (wherein R 1 represents a halogen atom; R 2 represents a C 1-12 alkyl group, a C 2-12 alkenyl group, a C 2-12 alkynyl group, a C 3-8 cycloalkyl g roup, an aryl group, an ar-C 1-6 alkyl group or a heterocyclic group, each opti onally having at least one substituent; R 3 represents an aryl group or a hetero cyclic group each optionally having at least one substituent; and R 4 and R 5 e ach independently represent a hydrogen atom; and R 2 and R 4 may form a cyc lic amino group optionally having at least one substituent together with the ni trogen atom to which they bind) or a salt thereof, and a pharmaceutical comp osition for use in the treatment of a Syk-related disease which comprises the nicotinamide derivative or a salt thereof.
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Paragraph 0814; 0815
(2018/09/08)
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- SUBSTITUTED [5,6]CYCLIC-4(3H)-PYRIMIDINONES AS ANTICANCER AGENTS
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The present invention relates to novel substituted [5,6]cyclic-4(3H)-pyrimidinone compounds of formula (I) and their preparation methods. (I) In particular, the present invention relates to novel substituted [5,6]cyclic-4(3H)- pyrimidinone compounds useful as inhibitors of protein kinases, specifically CDC7 (cell division cycle 7) inhibitors.
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- Catalytic Friedel–Crafts C?H Borylation of Electron-Rich Arenes: Dramatic Rate Acceleration by Added Alkenes
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In the electrophilic C?H borylation of electron-rich aromatic compounds with catecholborane, the catalytic generation of the boron electrophile is initiated by heterolysis of the B?H bond by various Lewis and Br?nsted acids, with a boronium ion formed exclusively. After ligand dissociation, the corresponding borenium ion undergoes regioselective electrophilic aromatic substitution on aniline derivatives as well as nitrogen-containing heterocycles. The catalysis is optimized using B(C6F5)3 as the initiator and proceeds without the addition of an external base or dihydrogen acceptor. Temperatures above 80 °C are generally required to secure efficient turnover in these Friedel–Crafts-type reactions. Mechanistic experiments reveal that regeneration of the boronium/borenium ion with dihydrogen release is rate-determining. This finding finally led to the discovery that, with added alkenes, catalytic C?H borylations can, for the first time, be carried out at room temperature.
- Yin, Qin,Klare, Hendrik F. T.,Oestreich, Martin
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supporting information
p. 3712 - 3717
(2017/03/21)
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- Catalytic aromatic borylation via in situ-generated borenium species
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We have developed a catalytic direct borylation of arenes via in situ-generated borenium species. The choice of appropriate Lewis base was crucial to achieve the catalytic system. Electron-rich arenes were borylated in a regioselective manner.
- Kitani, Fumiya,Takita, Ryo,Imahori, Tatsushi,Uchiyama, Masanobu
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p. 158 - 166
(2017/07/28)
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- Gold(I)/chiral br??nsted acid catalyzed enantioselective hydroamination-hydroarylation of alkynes: The effect of a remote hydroxyl group on the reactivity and enantioselectivity
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The catalytic enantioselective hydroamination-hydroarylation of alkynes under the catalysis of (R3P)AuMe/(S)-3,3a?2-bis(2,4,6-triisopropylphenyl)-1,1a?2-bi-naphthyl-2,2a?2-diyl hydrogenphosphate ((S)-TRIP) is reported. The alkyne was reacted with a range of pyrrole-based aromatic amines to give pyrrole-embedded aza-heterocyclic scaffolds bearing a quaternary carbon center. The presence of a hydroxyl group in the alkyne tether turned out to be very crucial for obtaining products in high yields and enantioselectivities. The mechanism of enantioinduction was established by carefully performing experimental and computational studies.
- Shinde, Valmik S.,Mane, Manoj V.,Vanka, Kumar,Mallick, Arijit,Patil, Nitin T.
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p. 975 - 979
(2015/02/05)
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- Metal-free catalytic C-H bond activation and borylation of heteroarenes
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Transition metal complexes are efficient catalysts for the C-H bond functionalization of heteroarenes to generate useful products for the pharmaceutical and agricultural industries. However, the costly need to remove potentially toxic trace metals from the end products has prompted great interest in developing metal-free catalysts that can mimic metallic systems.We demonstrated that the borane (1-TMP-2-BH2-C6H4)2 (TMP, 2,2,6,6-tetramethylpiperidine) can activate the C-H bonds of heteroarenes and catalyze the borylation of furans, pyrroles, and electron-rich thiophenes. The selectivities complement those observed with most transition metal catalysts reported for this transformation.
- Légaré, Marc-André,Courtemanche, Marc-André,Rochette, étienne,Fontaine, Frédéric-Georges
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p. 513 - 516
(2015/09/08)
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- A Palladium(II)-Catalyzed C-H Activation Cascade Sequence for Polyheterocycle Formation
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Polyheterocycles are found in many natural products and are useful moieties in functional materials and drug design. As part of a program towards the synthesis of Stemona alkaloids, a novel palladium(II)-catalyzed C-H activation strategy for the construction of such systems has been developed. Starting from simple 1,3-dienyl-substituted heterocycles, a large range of polycyclic systems containing pyrrole, indole, furan and thiophene moieties can be synthesized in a single step. Don't overdo it: A palladium(II)-catalyzed C-H activation cascade sequence for the synthesis of polyheterocycles is reported. Aromatization of the initially formed dihydro species occurred with a quinone oxidant. In some cases the use of one equivalent of the oxidant enabled isolation of the dihydro species as a single isomer (see scheme; X=NMe, O, S).
- Cooper, Stephen P.,Booker-Milburn, Kevin I.
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supporting information
p. 6496 - 6500
(2015/06/02)
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- Mechanistic studies into amine-mediated electrophilic arene borylation and its application in MIDA boronate synthesis
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Direct electrophilic borylation using Y2BCl (Y2 = Cl2 or o-catecholato) with equimolar AlCl3 and a tertiary amine has been applied to a wide range of arenes and heteroarenes. In situ functionalization of the ArBCl2 products is possible with TMS 2MIDA, to afford bench-stable and easily isolable MIDA-boronates in moderate to good yields. According to a combined experimental and computational study, the borylation of activated arenes at 20 C proceeds through an S EAr mechanism with borenium cations, [Y2B(amine)] +, the key electrophiles. For catecholato-borocations, two amine dependent reaction pathways were identified: (i) With [CatB(NEt 3)]+, an additional base is necessary to accomplish rapid borylation by deprotonation of the borylated arenium cation (σ complex), which otherwise would rather decompose to the starting materials than liberate the free amine to effect deprotonation. Apart from amines, the additional base may also be the arene itself when it is sufficiently basic (e.g., N-Me-indole). (ii) When the amine component of the borocation is less nucleophilic (e.g., 2,6-lutidine), no additional base is required due to more facile amine dissociation from the boron center in the borylated arenium cation intermediate. Borenium cations do not borylate poorly activated arenes (e.g., toluene) even at high temperatures; instead, the key electrophile in this case involves the product from interaction of AlCl3 with Y2BCl. When an extremely bulky amine is used, borylation again does not proceed via a borenium cation; instead, a number of mechanisms are feasible including via a boron electrophile generated by coordination of AlCl3 to Y2BCl, or by initial (heteroarene)AlCl3 adduct formation followed by deprotonation and transmetalation.
- Bagutski, Viktor,Del Grosso, Alessandro,Carrillo, Josue Ayuso,Cade, Ian A.,Helm, Matthew D.,Lawson, James R.,Singleton, Paul J.,Solomon, Sophia A.,Marcelli, Tommaso,Ingleson, Michael J.
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supporting information
p. 474 - 487
(2013/02/25)
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- Sterically controlled iodination of arenes via iridium-catalyzed C-H borylation
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A mild method to prepare aryl and heteroaryl iodides by sequential C-H borylation and iodination is reported. The regioselectivity of this process is controlled by steric effects on the C-H borylation step and is complementary to existing methods to form aryl iodides. The iodination of boronic esters has potential for the synthesis of radiolabeled aryl iodides, as demonstrated by the concise synthesis of a potential tracer for SPECT imaging.
- Partridge, Benjamin M.,Hartwig, John F.
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supporting information
p. 140 - 143
(2013/03/28)
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- PROCESS FOR THE BORYLATION OF ARENES AND HETEROARYLS
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This invention relates to a novel process for the borylation of arenes and heteroaryls. The present invention also provides novel borenium cations, which act as electrophiles for electrophilic substitution on the arene or heteroaryl ring, as well as to methodology for the preparation of these cations.
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Page/Page column 62-63
(2012/03/26)
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- Simple inexpensive boron electrophiles for direct arene borylation
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Electrophilic direct borylation is facilitated, and arene substrate scope enhanced, by using electrophiles derived from inexpensive reagents; specifically an amine, BCl3 and AlCl3.
- Del Grosso, Alessandro,Helm, Matthew D.,Solomon, Sophia A.,Caras-Quintero, Dolores,Ingleson, Michael J.
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p. 12459 - 12461
(2012/01/12)
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- Pinacol boronates by direct arene borylation with borenium cations
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Borenium does it direct: A boron analogue of the Friedel-Crafts reaction uses inexpensive catecholatoborenium cations that are sufficiently electrophilic to borylate arenes by electrophilic aromatic substitution. The direct arene borylation proceeds with high regioselectivity for a range of anilines, N-heterocycles, and thiophenes. Subsequent one-pot transesterification provides the synthetically useful pinacol boronate esters (see scheme).
- Del Grosso, Alessandro,Singleton, Paul J.,Muryn, Christopher A.,Ingleson, Michael J.
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p. 2102 - 2106
(2011/04/22)
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- Total synthesis of rhazinilam: Axial to point chirality transfer in an enantiospecific Pd-catalyzed transannular cyclization
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Figure Presented. A total synthesis of rhazinilam based on a transannular cyclization strategy is described. Using a Heck reaction, the axial chirality of a halogenated 13-membered lactam can be exploited to create the quaternary chiral stereogenic center in the target molecule with high enantiospecificity.
- Gu, Zhenhua,Zakarian, Armen
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supporting information; experimental part
p. 4224 - 4227
(2010/11/17)
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- Synthesis of pyrrolnitrin and related halogenated phenylpyrroles
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A general approach to halogenated arylpyrroles, including the antifungal natural product pyrrolnitrin, is described using newly synthesized halogenated pyrroles and 2,6-disubstituted nitrobenzenes or 2,6-disubstituted anilines.
- Morrison, Matthew D.,Hanthorn, Jason J.,Pratt, Derek A.
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body text
p. 1051 - 1054
(2009/07/18)
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- Synthesis of the pyrrolo[2,3-c]carbazole core of the dictyodendrins
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The pyrrolo[2,3-c]carbazole 1, the common core of the marine alkaloids known as the dictyodendrins, has been synthesised. The sequence is based on a Suzuki cross-coupling reaction between the pyrrole fragment 2 and the indole fragment 3, followed by tandem photochemical 6π-electrocyclisation/ aromatisation.
- Ayats, Carles,Soley, Roger,Albericio, Fernando,Alvarez, Mercedes
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p. 860 - 862
(2009/05/30)
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- An improved system for the palladium-catalyzed borylation of aryl halides with pinacol borane
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(Chemical Equation Presented) borylation of aryl halides with an inexpensive and atom-economical boron source, pinacol borane, has been developed. This system allows for the conversion of aryl and heteroaryl iodides, bromides, and several chlorides, containing a variety of functional groups, to the corresponding pinacol boronate esters. In addition to the increase in substrate scope, this is the first general method where relatively low quantities of catalyst and short reaction times can be employed.
- Billingsley, Kelvin L.,Buchwald, Stephen L.
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p. 5589 - 5591
(2008/12/20)
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- Synthesis of rhazinicine by a metal-catalyzed C-H bond functionalization strategy
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(Chemical Equation Presented) Iterative and regioselective metal-catalyzed C-H bondfunctionalization has been utilizedto develop a strategy for the first total synthesis of the pyrrole alkaloid rhazinicine (see scheme).
- Beck, Elizabeth M.,Hatley, Richard,Gaunt, Matthew J.
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p. 3004 - 3007
(2008/12/23)
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- Highly efficient monophosphine-based catalyst for the palladium-catalyzed Suzuki-Miyaura reaction of heteroaryl halides and heteroaryl boronic acids and esters
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A highly active and efficient catalyst system derived from a palladium precatalyst and monophosphine ligands 1 or 2 for the Suzuki-Miyaura cross-coupling reaction of heteroaryl boronic acids and esters has been developed. This method allows for the preparation of a wide variety of heterobiaryls in good to excellent yields and displays a high level of activity for the coupling of heteroaryl chlorides as well as hindered aryl and heteroaryl halides. Specific factors that govern the efficacy of the transformation for certain heterocyclic motifs were also investigated.
- Billingsley, Kelvin,Buchwald, Stephen L.
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p. 3358 - 3366
(2007/10/03)
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- A highly active catalyst for Suzuki-Miyaura cross-coupling reactions of heteroaryl compounds
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(Chemical Equation Presented) Unprecedented activity: Catalysts derived from Pd and bulky dialkylphosphinobiaryl ligands are shown to be highly stable and active in Suzuki-Miyaura reactions of heteroaryl halides and heteroaryl boronic acids/esters (e.g., 3-or 4-pyridine, indole, and N-protected pyrrole derivatives). Furthermore, this catalyst system is not inhibited by the presence of highly basic aminopyridines or aminopyrimidines.
- Billingsley, Kelvin L.,Anderson, Kevin W.,Buchwald, Stephen L.
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p. 3484 - 3488
(2007/10/03)
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- PROCESS FOR PRODUCTION OF HETEROARYL-TYPE BORON COMPOUNDS WITH IRIDIUM CATALYST
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The present invention provides an economically and industrially superior simple process that enables the selective production of an aromatic heterocyclic monoboron compound and aromatic heterocyclic diboron compound at a satisfactory yield and in a desired ratio by reacting an aromatic heterocyclic compound and a boron compound in a single step under mild conditions while changing only the charged ratios of the raw materials. The present invention provides a production process of a heteroaryl mono- or diboron compound comprising an aromatic heterocyclic compound and a boron compound in the form of bis(pinacolate)diboron or pinacolate diborane in the presence of a iridium-containing catalyst and a ligand such as a bipyridyl ligand.
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- Iridium-catalyzed C-H coupling reaction of heteroaromatic compounds with bis(pinacolato)diboron: Regioselective synthesis of heteroarylboronates
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The C-H coupling of aromatic heterocycles with bis(pinacolato)diboron was carried out in octane at 80-100°C in the presence of a 1/2[IrCl(COD)]2-(4,4′-di-tert-butyl-2,2′-bipyridine) catalyst (3 mol%). The reactions of five-membered substrates such as thiophene, furan, pyrrole, and their benzo-fused derivatives exclusively produced 2-borylated products, whereas those of six-membered heterocycles including pyridine and quinoline selectively occurred at the 3-position. Regioselective synthesis of bis(boryl)heteroaromatics was also achieved by using an almost equimolar amount of substrates and the diboron.
- Takagi, Jun,Sato, Kazuaki,Hartwig, John F,Ishiyama, Tatsuo,Miyaura, Norio
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p. 5649 - 5651
(2007/10/03)
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- Regioselective aromatic borylation in an inert solvent.
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[reaction: see text]. A protocol for performing Rh catalyzed aromatic borylations in cyclohexane has been devised. Borylation at the 5-position of several 1,3-substituted aromatic species ranging from electron-rich (1,3-(NMe(2))(2)C(6)H(4)) to electron-deficient (1,3-(CF(3))(2)C(6)H(4)) yields the corresponding aryl boronate esters. Veratrole was selectively borylated at the 4-position, thus extending regioselectivity to 1,2-substituted benzenes. Selective borylation at the 3-position of an N-protected pyrrole has also been demonstrated, providing a valuable reagent for cross-coupling reactions in a single step.
- Tse,Cho,Smith 3rd.
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p. 2831 - 2833
(2007/10/03)
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