33332-29-5Relevant academic research and scientific papers
The complete synthesis of favipiravir from 2-aminopyrazine
Guo, Qi,Xu, Mingshuo,Guo, Shuang,Zhu, Fuqiang,Xie, Yuanchao,Shen, Jingshan
, p. 1043 - 1051 (2019/04/25)
Favipiravir was first synthesized from an inexpensive and commercially available starting material, 2-aminopyrazine. The preferred route embedded within Scheme?4 consisted of seven steps, and was highlighted by the novel and efficient synthesis of 3,6-dichloropyrazine-2-carbonitrile 8. This intermediate was prepared in four successive steps which were regioselective chlorination of the pyrazine ring, bromination, Pd-catalyzed cyanation, and Sandmeyer diazotization/chlorination. This protocol eliminated the hazardous POCl3 of previous synthetic methods and offered a better yield (48%) which was 1.3-fold higher than a recently published procedure. From intermediate 8, the subsequent nucleophilic fluorination, nitrile hydration and hydroxyl substitution efficiently afforded the target product. Another synthetic approach with the same starting material was also investigated to bypass the allergy-causing dichloro intermediate 8. However, the key step of monofluorination at the pyrazine C6 position of intermediate 19 or 22 was not achieved.
Selectfluor-promoted regioselective chlorination/bromination of 2-aminopyridines and 2-aminodiazines using LiCl/LiBr
Hu, Jiao,Zhou, Gang,Tian, Yawei,Zhao, Xiaoming
supporting information, p. 6342 - 6345 (2019/07/10)
Using LiCl as a chlorine source, the chlorination of 2-aminopyridines or 2-aminodiazines in the presence of Selectfluor and DMF is established under mild conditions. This method gives chlorinated pyridines or diazines in good to high yields with high regioselectivities. Also, this method is extended to the bromination of 2-aminopyridines or 2-aminodiazines by using LiBr. The regioselectivity of the chlorination reaction is strongly dependent upon the substituent pattern in either the 2-aminopyridines or 2-aminodiazines. The synthesis of Buparlisib from chlorinated pyridines was explored. A study of the mechanism revealed that this chlorination occurs via either a pyridine or diazine radical process.
Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents
Guo, Shuang,Xu, Mingshuo,Guo, Qi,Zhu, Fuqiang,Jiang, Xiangrui,Xie, Yuanchao,Shen, Jingshan
, p. 748 - 759 (2019/01/26)
To explore the application potential of dual prodrug strategies in the development of anti-HCV agents, a variety of sofosbuvir derivatives with modifications at the C4 or N3 position of the uracil moiety were designed and synthesized. Some compounds exhibited potent anti-HCV activities, such as 4e and 8a–8c with similar EC50 values (0.20–0.22 μM) comparative to that of sofosbuvir (EC50 = 0.18 μM) in a genotype 1b based replicon Huh-7 cell line. Moreover, 8b displayed a good human plasma stability profile, and was easily metabolized in human liver microsomes expectantly. On the other hand, aiming to discover novel anti-HCV nucleosides, pyrazin-2(1H)-one nucleosides and their phosphoramidate prodrugs were investigated. Several active compounds were discovered, such as 25e (EC50 = 7.3 μM) and S-29b (EC50 = 19.5 μM). This kind of nucleosides were interesting and would open a new avenue for the development of antiviral agents.
Efficient Halogenation of 2-Aminopyrazine
Grima, Josep,Lizano, Enric,Pujol, M. Dolors
, p. 2000 - 2003 (2019/10/22)
2-Aminopyrazine was halogenated with NIS, NCS, and NBS under different reaction conditions. Chlorination and bromination were achieved with good yields by using acetonitrile as the solvent. However, iodination was only obtained in poor yields. Undoubtedly, the best conditions for both mono-and dihalogenation were the use of NBS, acetonitrile, and microwave assistance for short periods. 3,5-Dibromo-2-Aminopyrazine is an excellent functionalized starting material for the synthesis of nitrogen heterocycles.
NOVEL COMPOUNDS AS GPR119 AGONISTS
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Paragraph 0562-0564, (2017/10/26)
The present invention relates to novel compounds of formula (I) as GPR119 agonist, composition compositions containing such compounds and method of preparation thereof.
N-Chloro-N-methoxybenzenesulfonamide: A Chlorinating Reagent
Pu, Xiaoqiu,Li, Qingwei,Lu, Zehai,Yang, Xianjin
supporting information, p. 5937 - 5940 (2016/12/26)
A structurally simple and reactive chlorinating reagent, N-chloro-N-methoxybenzenesulfonamide, was conveniently and economically prepared in high yield. 1,3-Diketones, β-keto esters, benzoyl trifluoroacetones, phenols, anisoles, heteroarenes, and aromatic amines were successfully chlorinated, and the products were obtained in good to high yields.
A new class of pyrazolopyridine nucleus with fluorescent properties, obtained through either a radical or a Pd arylation pathway from N-azinylpyridinium N-aminides
Abet, Valentina,Nunez, Araceli,Mendicuti, Francisco,Burgos, Carolina,Alvarez-Builla, Julio
supporting information; scheme or table, p. 8800 - 8807 (2009/04/11)
(Chemical Equation Presented) The synthesis of dipyridopyrazole and pyridopyrazolopyrazine derivatives - both of which incorporate a 3-aryl moiety - can be achieved in moderate yields by intramolecular radical arylation of pyridinium N-aminides using tris(trimethylsilyl)silane and azobisisobutyronitrile. Improved results were obtained on using Pd direct arylation in conjunction with microwave irradiation. A preliminary study into the fluorescent properties of the target compounds is also reported.
BIPIPERIDINYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT
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Page/Page column 53, (2008/12/07)
Bipiperidinyl compounds of the formula I, are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. Pharmaceutically acceptable salts and solvates are included as well. The compounds are useful as agonists of the g-protein coupled receptor GPR-119.
BETA-AMYLOID PET IMAGING AGENTS
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Page/Page column 26-27, (2008/06/13)
Novel derivatives of imidazopyridinylbenzeneamines and novel derivatives of benzothiazolylbenzeneamines are disclosed that offer improved behavior when used as imaging agents for positron emission tomography of beta-amyloids. Also disclosed is a palladium-catalyzed reaction scheme under microwave conditions for aryl thioethers in general that provides a high ratio of substitution relative to reduction and can be used for the imidazopyridinylbenzeneamine derivatives as well as other compounds of related structure.
Synthesis and structure-affinity relationships of new 4-(6-iodo-H- imidazo[1,2-a]pyridin-2-yl)-N-dimethylbenzeneamine derivatives as ligands for human β-amyloid plaques
Cai, Lisheng,Cuevas, Jessica,Temme, Sebastian,Herman, Mary M.,Dagostin, Claudio,Widdowson, David A.,Innis, Robert B.,Pike, Victor W.
, p. 4746 - 4758 (2008/03/14)
A new and extensive set of 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N- dimethylbenzeneamine (IMPY) derivatives was synthesized and assayed for affinity toward human Aβ plaques. 6-Ethylthio- (12h), 6-cyano-(12e), 6-nitro- (12f), and 6-p-methoxybenzylthio- (15d) analogues were discovered to have high affinity (KI I = 7.4 nM) whereas a methyl substituent did not (14c). The tolerance for nonhydrophilic thioether substituents in the 6-position opens up the possibility of developing new sensitive positron emission tomography radioligands for imaging human Aβ plaques in Alzheimer's disease, especially in view of the amenability of thioethers to be labeled with carbon-11 or fluorine-18 through S-alkylation reactions. The structure-activity relationships revealed in this study extends insight into the topography of the binding site for IMPY-like ligands in human Aβ plaques.
