5621-02-3Relevant articles and documents
Amination of Aromatic Halides and Exploration of the Reactivity Sequence of Aromatic Halides
Yang, Chu,Zhang, Feng,Deng, Guo-Jun,Gong, Hang
, p. 181 - 190 (2019/01/10)
A base-promoted amination of aromatic halides has been developed using a limited amount of dimethylformamide (DMF) or amine as an amino source. Various aryl halides, including F, Cl, Br, and I, have been successfully aminated in good to excellent yields. Although the amination of aromatic halides with amines or DMF is usually considered as an aromatic nucleophilic substitution (SNAr) process, and the reactivity of an aromatic halide is F > Cl > Br > I, the reactivity of aromatic halides in this system was found to be I > Br a‰ F > Cl. This protocol also showed a good regioselectivity for multihalogenated aromatics. This protocol is valuable for industrial application due to the simplicity of operation, the unrestricted availability of amino sources and aromatic halides, transition metal-free conditions, no requirement for solvent, and scalability.
Site-Selective C–H Functionalization of (Hetero)Arenes via Transient, Non-symmetric Iodanes
Fosu, Stacy C.,Hambira, Chido M.,Chen, Andrew D.,Fuchs, James R.,Nagib, David A.
supporting information, p. 417 - 428 (2019/02/14)
Fosu, Hambira, and colleagues describe the direct C–H functionalization of medicinally relevant arenes or heteroarenes. This strategy is enabled by transient generation of reactive, non-symmetric iodanes from anions and PhI(OAc)2. The site-selective incorporation of Cl, Br, OMs, OTs, and OTf to complex molecules, including within medicines and natural products, can be conducted by the operationally simple procedure included herein. A computational model for predicting site selectivity is also included. The discovery of new medicines is a time- and labor-intensive process that frequently requires over a decade to complete. A major bottleneck is the synthesis of drug candidates, wherein each complex molecule must be prepared individually via a multi-step synthesis, frequently requiring a week of effort per molecule for thousands of candidates. As an alternate strategy, direct, post-synthetic functionalization of a lead candidate could enable this diversification in a single operation. In this article, we describe a new method for direct manipulation of drug-like molecules by incorporation of motifs with either known pharmaceutical value (halides) or that permit subsequent conversion (pseudo-halides) to medicinally relevant analogs. This user-friendly strategy is enabled by combining commercial iodine reagents with salts and acids. We expect this simple method for selective, post-synthetic incorporation of molecular diversity will streamline the discovery of new medicines. A strategy for C–H functionalization of arenes and heteroarenes has been developed to allow site-selective incorporation of various anions, including Cl, Br, OMs, OTs, and OTf. This approach is enabled by in situ generation of reactive, non-symmetric iodanes by combining anions and bench-stable PhI(OAc)2. The utility of this mechanism is demonstrated via para-selective chlorination of medicinally relevant arenes, as well as site-selective C–H chlorination of heteroarenes. Spectroscopic, computational, and competition experiments describe the unique nature, reactivity, and selectivity of these transient, unsymmetrical iodanes.
Antibacterial activity and mechanism of action of the benzazole acrylonitrile-based compounds: In?vitro, spectroscopic, and docking studies
AlNeyadi, Shaikha S.,Salem, Alaa A.,Ghattas, Mohammad A.,Atatreh, Noor,Abdou, Ibrahim M.
, p. 270 - 282 (2017/05/15)
A new series of pyrimidine derivatives 5, 9a-d and 12a-d was synthesized by an efficient procedure. The antibacterial activity of the new compounds was studied against four bacterial strains. Compound 5 was found to exhibit the highest potency, with?=?1.0?μg/ml, against both Escherichia coli and Pseudomonas aeruginosa when compared with amoxicillin (MIC?=?1.0–1.5?μg/mL). Transmission electron microscope results confirmed that activities against bacteria occurred via rupturing of the cell wall. Molecular modeling results suggested that compounds 5, 9a-d and 12a-d have the potential to irreversibly bind to the penicillin-binding protein (PBP) Ser62 residue in the active site and were able to overcome amoxicillin resistance in bacteria by inhibiting the β-lactamase enzyme. Docking studies showed that compounds 5, 9a-d and 12a-d inhibit the β-lactamase enzyme through covalent bonding with Ser70. The synergistic effect with amoxicillin was studied. The newly synthesized compounds reported in this study warrant further consideration as prospective antimicrobial agents.
Iridium- and rhodium-catalyzed dehydrogenative silylations of C(sp 3) - H bonds adjacent to a nitrogen atom using hydrosilanes
Mita, Tsuyoshi,Michigami, Kenichi,Sato, Yoshihiro
supporting information, p. 2970 - 2973 (2014/01/06)
Now that is just silylated: In the presence of iridium or rhodium catalysts, C(sp3) - H bonds adjacent to a nitrogen atom were silylated by the aid of a pyridine-directing group. In iridium catalysis, a hydrogen-trapping reagent such as norbornene or tert-butylethylene, which is usually required in late transition-metal-catalyzed dehydrogenative coupling reactions, was not required. In rhodium catalysis, however, 1 equivalent of COD (1,5-cyclooctadiene) was necessary to induce higher conversion. Copyright
Amidine dications: Isolation and [Fe]-hydrogenase-related hydrogenation
Corr, Michael J.,Gibson, Kirsty F.,Kennedy, Alan R.,Murphy, John A.
supporting information; experimental part, p. 9174 - 9175 (2009/12/05)
(Chemical Equation Presented) This commmunication demonstrates the preparation, isolation, and full characterization of superelectrophilic salts based on amidine dications in organic solvent, as their triflate salts. These dications are highly activated toward regiospecific reaction with hydrogen gas under mild conditions in the presence of a metal catalyst (Pd/C), mimicking the behavior of the natural substrate, N5,N10- methenyltetrahydromethanopterin, in the iron-sulfur cluster-free [Fe]-hydrogenase.
Amidine dications as superelectrophiles
Corr, Michael J.,Roydhouse, Mark D.,Gibson, Kirsty F.,Zhou, Sheng-Ze,Kennedy, Alan R.,Murphy, John A.
supporting information; experimental part, p. 17980 - 17985 (2010/04/01)
2-Dimethylalkylammonium pyridinium and 2-dimethylalkylammonium pyrimidinium ditriflate salts are very powerful methylating agents toward phosphorus (triphenylphosphine) and nitrogen (triethylamine) nucleophiles. In competition experiments with triethylamine as nucleophile, these N-methyl disalts are more reactive methylating agents than dimethyl sulfate. Reaction of the pyridinium dications with water as an oxygen nucleophile leads to attack at the 2-position of the heteroaromatic ring and displacement of an ammonium group; 2-hydroxypyridinium compounds are formed in the first instance, which are easily converted to 2-pyridones. Extending the scope of the reactions, a tricationic 2,6-bis(dimethylalkylammonium) pyridinium salt has also been prepared and characterized and its reactivity as a methylating agent assessed in comparison with that of the dications.
Benzimidazole compounds, pharmaceutical compositions containing the compounds and their use
-
, (2008/06/13)
The present patent application discloses compounds having the formula STR1 or a pharmaceutically acceptable salt thereof or an oxide thereof wherein R 3 is STR2 wherein A, B and D each is CH, or one or two of A, B and D is N and the others are CH;R 11 is
A very convenient dimethylamination of activated aromatic halides using N,N-dimethylformamide and ethanolamines
Cho, Yoon Hwan,Park, Jae Chan
, p. 8331 - 8334 (2007/10/03)
A very convenient dimethylamination of activated aromatic halides was achieved by using N,N-dimethylformamide(DMF) and ethanolamines. p- Nitrochlorobenzene, 2-halopyridines, 2-chloroquinoline and 2-chloropyrimidine gave the corresponding dimethylamino substituted products when treated with DMF and diethanolamine in 80-92% yield.
Synthesis and cardiotonic activity of novel pyrimidine derivatives: Crystallographic and quantum chemical studies
Dorigo, Paola,Fraccarollo, Daniela,Santostasi, Giovanni,Maragno, Ildebrando,Floreani, Maura,Borea, Pier Andrea,Mosti, Luisa,Sansebastiano, Laura,Fossa, Paola,Orsini, Fulvia,Benetollo, Franco,Bombieri, Gabriella
, p. 3671 - 3683 (2007/10/03)
The synthesis of ethyl or methyl 4-substituted or unsubstituted 2- (dimethylamino)-5-pyrimidinecarboxylates 10-20, which is mainly carried out by reaction of ethyl or methyl 2-[(dimethylamino)methylene]-3-oxoalkanoates with 1,1-dimethylguanidine, is described. The above esters were hydrolyzed to the relative carboxylic acids 21-30, which were decarboxylated to the corresponding 2,4-disubstituted pyrimidines 31-40. All the new synthesized pyrimidines were evaluated in spontaneously beating and electrically driven atria from reserpine-treated guinea pigs. Their effects were compared to those induced by milrinone in both atria preparations. Compound 28 (4- benzyl-2-(dimethylamino)-5-pyrimidinecarboxylic acid) was the most effective positive inotropic agent, while the corresponding methyl ester 17 reduced both the contractile force and the frequency of guinea pig atria. An antagonism toward the negative influence exerted by endogenous adenosine on the heart seems to be involved in the contractile activity of compound 28. By contrast, compound 17 might be partial agonist at the purinergic inhibitory (A1) receptor. X-ray analysis carried out on 17 and 28 and molecular modeling investigations extended also to related derivatives allowed a possible rationalization between structure and inotropic activity for this series of compounds.
Selectivity in consecutive S(N)Ar-dequaternization reactions of chlorodiazines with tertiary amines
Matsumoto,Hashimoto,Hashimoto,Toda,Otani
, p. 787 - 792 (2007/10/02)
Consecutive S(N)Ar-dealkylation reactions of chlorodiazines such as 2-chloropyrimidine and 3,6-dichloropyridazine with tertiary amines took place in a highly selective fashion.
