449758-17-2Relevant articles and documents
Green protection of pyrazole, thermal isomerization and deprotection of tetrahydropyranylpyrazoles, and high-yield, one-pot synthesis of 3(5)-alkylpyrazoles
Ahmed, Basil M.,Mezei, Gellert
, p. 24081 - 24093 (2015)
We report a new synthetic approach that opens up the possibility of large scale, one-pot pyrazole derivatization by a wide variety of functionalities, including alkyl, halogen, hydroxyl, amino, azido, carbonyl, and organo-element (e.g., B, Si, P) groups. The approach is illustrated by the highly efficient synthesis of fourteen 3(5)-alkylpyrazoles, including the novel isopentyl- and n-hexadecyl derivatives, as well as 1,6-bis(pyrazol-3(5)-yl)hexane. The value of the new approach lies in the discovery of a green (solvent- and catalyst-free, quantitative) protection of pyrazole, followed by a high-yield lithiation/alkylation/deprotection sequence in the same pot. For the first time, the corresponding N-tetrahydropyran-2-yl (THP) intermediates have been isolated and characterized. Thermal isomerization of the 5-alkyl-1-(THP) to the 3-alkyl-1-(THP) isomer is shown to be an advantageous, green alternative to the acid-catalyzed, sequential protecting-group switching methodology in pyrazole chemistry. The X-ray crystal structures of 1,6-bis(pyrazol-3(5)-yl)hexane and 5-n-hexadecyl-1-(tetrahydropyran-2-yl)pyrazole reveal supramolecular architectures that shine light on the remarkable affinity for water and unexpected insolubility in organic solvents of alkylene-bridged bis(pyrazoles). 3(5)-Alkylpyrazoles are obtained in high yield from pyrazole by a one-pot procedure.
Thiofunctionalization of Electron-Rich Heteroarenes through Magnesiation and Trapping with Octasulfur
Vera, Gonzalo,Mangeant, Reynald,Stiebing, Silvia,Berhault, Yohann,Fabis, Frédéric,Cailly, Thomas,Collot, Valérie
supporting information, p. 5099 - 5105 (2021/09/25)
Herein we report a site-selective and thiol-free thiofunctionalization of electron-rich heteroarenes. After a selective ortho-magnesiation, the use of S8 followed by an electrophile allows direct access to S-alkyl or -aryl derivatives. In situ oxidation provides the corresponding sulfoxide and sulfone derivatives. Applying this protocol, Cerlapirdine was prepared in 4 steps with 28% overall yield. (Figure presented.).
HETEROCYCLIC COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
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Paragraph 0431-0432, (2022/01/01)
The present invention relates to a heterocyclic compound, a pharmaceutical composition comprising same, a preparation method therefor, and a use thereof. Specifically, the compound of the present invention is represented by formula (I), and used for preventing or treating a disease or condition related to RET activity.
GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 002214; 002215; 002217; 002239; 002240; 002241, (2019/07/17)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme glycolate oxidase (GO). Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.