- Synthesis of 2-Alkylamino-3-fluoropyridines Using Buchwald Conditions
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Synthesis of 2-alkylamino-3-fluoropyridines from 2-chloro-3-fluoropyridine using palladium-catalyzed coupling reaction under Buchwald conditions is described.
- Munson, Peter M.,Thompson, Wayne J.
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- Thorpe–Ingold Effect in Branch-Selective Alkylation of Unactivated Aryl Fluorides
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Presented herein is a general protocol for the alkylation of simple aryl fluorides with unbiased secondary Grignard reagents by means of nickel catalysis. This study revealed a general Thorpe–Ingold effect in the ligand backbone which confers a high degree of selectivity for the secondary carbon center in the C?C coupling event. This protocol is characterized by mild reaction conditions, robustness, and simplicity. Both electron-rich and electron-deficient aryl fluorides are suitable candidates in this transformation. Equally amenable are a variety of heterocycles, permitting the coupling without over alkylation at the electrophilic sites.
- O'Neill, Matthew J.,Riesebeck, Tim,Cornella, Josep
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supporting information
p. 9103 - 9107
(2018/07/24)
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- Benzimidazoles that are useful in treating sexual dysfunction
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The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction, wherein L is C1-4 alkyl;RA, RB, RC, RD, and RE, are as described in the specification;Z is selected from the group consisting of N, C and CH; andA is aryl and heteroaryl as described in the specification.
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- Benzimidazoles that are useful in treating sexual dysfunction
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The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.
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- Discovery of 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole (ABT-724), a dopaminergic agent with a novel mode of action for the potential treatment of erectile dysfunction
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A new class of agents with potential utility for the treatment of erectile dysfunction has been discovered, guided by the hypothesis that selective D 4 agonists are erectogenic but devoid of the side effects typically associated with dopaminergic agents. The lead agent 2-(4-pyridin-2-ylpiperazin- 1-ylmethyl)-1H-benzimidazole (1, ABT-724) was discovered by optimization of a series of benzimidazole arylpiperazines. This highly selective D4 agonist was found to be very potent and efficacious in vivo, eliciting penile erections in rats at a dose of 0.03 μmol/kg, with a positive response rate of 77% erectile incidence. Even at high doses, it was devoid of side effects in animal models of central nervous system behaviors, emesis, or nausea. The structure-activity relationship of the parent benzimidazole series leading to 1 is described, with the detailed in vitro and in vivo profiles described. Distinctive structural features were discovered that are associated with D 4 selective agonism in this series of analogues.
- Cowart, Marlon,Latshaw, Steven P.,Bhatia, Pramila,Daanen, Jerome F.,Rohde, Jeffrey,Nelson, Sherry L.,Patel, Meena,Kolasa, Teodozyi,Nakane, Masaki,Uchic, Marie E.,Miller, Loan N.,Terranova, Marc A.,Chang, Renjie,Donnelly-Roberts, Diana L.,Namovic, Marian T.,Hollingsworth, Peter R.,Martino, Brenda R.,Lynch III, James J.,Sullivan, James P.,Hsieh, Gin C.,Moreland, Robert B.,Brioni, Jorge D.,Stewart, Andrew O.
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p. 3853 - 3864
(2007/10/03)
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- Benzimidazoles that are useful in treating sexual dysfunction
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The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.
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- IMIDAZO-PYRIDINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS
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A class of 8-fluoro-3-phenylimidazo[1,2-a]pyridine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group, or by a pyrrolidinonyl group, which is directly attached or bridged by an oxygen atom or by a -NH- or -OCH2- linkage, being selective ligands for GABAA receptors, in particular having high affinity for the α2 and/or α3 and/or α5 subunit thereof, are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.
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- 8-FLUORIMIDAZO`1,2-A!PYRIDINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS
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A class of 8-fluoroimidazo[1,2-a]pyridine derivatives, substituted at the 3-position by an optionally substituted five-membered or six-membered heteroaromatic ring, being selective ligands for GABAA receptors, in particular having high affinity for the α2 and/or α3 and/or α5 subunit thereof, are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.
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- Benzimidazoles that are useful in treating sexual dysfunction
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The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.
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- Benzimidazoles that are useful in treating sexual dysfunction
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The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.
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- Facile preparation of aromatic fluorides by deaminative fluorination of aminoarenes using hydrogen fluoride combined with bases
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One-pot deaminative fluorination of aminoarenes including heteroaromatics, namely, diazotization of aminoarenes followed by in situ fluoro-dediazoniation of the corresponding diazonium ions, was successfully accomplished to produce fluoroarenes in high yields by using hydrogen fluoride combined with base solutions. The diazotization stage has been found to play the most important part in yielding fluoroarenes effectively. It was greatly influenced by the composition of the HF solution and enhanced by employing appropriate amounts of bases such as pyridine under carefully controlled conditions. The fluoro-dediazoniation stage was effectively accelerated photochemically to afford fluoroarenes having polar substituents such as hydroxyl, nitro and so on in high yields.
- Yoneda,Fukuhara
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- A new convergent synthesis of alpha-substituted-beta-carbolines
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New convergent synthesis of natural α-substituted-β-carbolines through metalations, cross-couplings and intramolecular substitutioin via (2-aminobenzene)-boronic acid, arylstannanes and ortho-fluoroiodopyridines.
- Rocca,Marsais,Godard,Queguiner
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p. 3325 - 3342
(2007/10/02)
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- Utilizing Acetyl Hypofluorite for Chlorination, Bromination, and Etherification of the Pyridine System
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Acetyl hypofluorite, which is easily made from F2, possesses a strong electrophilic fluorine.This electrophile is able to attach itself to the nitrogen atom of pyridine and activate the ring toward nucleophilic attacks.The ultimate elimination of HF results in an overall easy nucleophilic displacement of the hydrogen of the important 2-position .The nucleophiles used: Clδ-, Brδ-, ROδ-, originate from solvents such as CH2Cl2, CH2Br2, and various primary alcohols.Thus, 2-halo- or 2-alkoxypyridines were formed.The reaction conditions (room temperature, very short reaction times, and good yields) transform the task of direct substitution of the pyridine ring from an extremely difficult to a very easy procedure.
- Hebel, David,Rozen, Shlomo
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p. 6298 - 6301
(2007/10/02)
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- SYNTHESIS OF ORELLANINE, THE LETHAL POISON OF A TOADSTOOL
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A ten step synthesis of the structure of orellanine, 3,3',4,4'- hydroxy-2,2'-bipyridyl-bis-N-oxide (1a), is described which proves the identity of the natural product.
- Dehmlow, Eckehard, V.,Schulz, Hans-Joachim
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p. 4903 - 4906
(2007/10/02)
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- NEW DEVELOPMENTS IN THE SYNTHESIS OF LOWER FLUORINATED PYRIDINES VIA DIAZOTIZATION-FLUORINATION OF AMINOPYRIDINES IN ANHYDROUS HYDROGEN FLUORIDE
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The isolation and stabilization of elusive 4-fluoropyridine as the hydrochloride salt (54percent yield) from fluorodediazoniation of 4-aminopyridine in anhydrous hydrogen fluoride (AHF) is described.Unlike the low yields (0-13percent) recently reported from the chlorodediazoniation of 2,6-diaminopyridine and 3-halo-2,6-diaminopyridine, fluorodediazoniation gave high yields (49-62percent) of the corresponding 2,6-difluoropyridines.In contrast, benzene analogs, i.e. m-phenylenediamine and 4-chloro-m-phenylenediamine, form only tars under similar fluorination conditions.Vicinal aminohalopyridines, e.g. 3-amino-2-chloropyridine and 2-amino-3,5-dichloropyridine give the corresponding fluorohalopyridine in 49-89percent yield.Again, the benzene analogs, i.e. o-chloroaniline and 2,4-dichloroaniline, resist fluorination.
- Boudakian, Max M.
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p. 497 - 506
(2007/10/02)
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