503627-65-4Relevant articles and documents
Synthetic method of aromatic ring group or aromatic heterocyclic tetrazole
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Paragraph 0036-0042; 0051, (2020/12/30)
The synthetic method comprises the following steps: (1) reacting 1.0 eq of ArI or HArI with 1.2 eq of ethyl 2, 2-difluoroacetate in the presence of DMSO as a solvent and 4.0 eq of Cu under the protection of nitrogen at 30 DEG C and 50 DEG C, and purifying to obtain a first intermediate compound; (2) dissolving 1.0 eq of the first intermediate compound in a mixed solvent of THF and water, adding 2.0 eq of LiOH, reacting at room temperature for 2 hours, spin-drying the solvent, adding HCl until the pH value is equal to 3, and filtering to obtain a second intermediate compound; and (3) reacting 1.0 eq of the second intermediate compound with 2.0 eq of diphenyl azide phosphate in the presence of 2.5 eq of triethylamine by taking tert-butyl alcohol as a solvent to generate aromatic ring group or aromatic heterocyclic tetrazole. The invention provides a novel synthetic method of aromatic ring group or aromatic heterocyclic tetrazole, wherein a target compound can be more conveniently obtained, and reagents participating in the reaction are low in toxicity, mild in reaction condition, simple and safe in aftertreatment, good in product quality and suitable for large-scale production.
Orally efficacious thrombin inhibitors with cyanofluorophenylacetamide as the P2 motif
Kreutter, Kevin D.,Lu, Tianbao,Lee, Lily,Giardino, Edward C.,Patel, Sharmila,Huang, Hui,Xu, Guozhang,Fitzgerald, Mark,Haertlein, Barbara J.,Mohan, Venkatraman,Crysler, Carl,Eisennagel, Stephen,Dasgupta, Malini,McMillan, Martin,Spurlino, John C.,Huebert, Norman D.,Maryanoff, Bruce E.,Tomczuk, Bruce E.,Damiano, Bruce P.,Player, Mark R.
, p. 2865 - 2870 (2008/12/21)
2-Cyano-6-fluorophenylacetamide was explored as a novel P2 scaffold in the design of thrombin inhibitors. Optimization around this structural motif culminated in 14, which is a potent thrombin inhibitor (Ki = 1.2 nM) that exhibits robust effica
