780705-64-8Relevant academic research and scientific papers
ANTIVIRAL COMPOUNDS
-
Paragraph 90-92; 95-96; 143-145, (2020/11/12)
The invention is provides novel antiviral compounds, as well as derivatives thereof. The compounds of the invention are preferably formulated as pharmaceuticals. The invention provides the compounds for use in the prevention and treatment of infectious diseases, in particular viral diseases. In some aspects the invention is based on the antiviral activity of the provided compounds against the Chikungunya virus, and hence, their application in the treatment or prevention of any physiological manifestation of such viral infection.
An improved synthesis of the 5-HT1A receptor agonist Eptapirone free base
Peng, Wei,Chen, Jian,Liu, Hui,Li, Xiufang,Deng, Zhiwei,Yuan, Jing,Peng, Yizhou,Yang, Yanjing,Zhong, Shian
, p. 1321 - 1331 (2019/05/06)
Eptapirone free base, F11440,4-methyl-2-(4-(4-(pyrimidin-2-yl)piperazin-1-yl)butyl)-1,2,4-triazine-3,5(2H,4H)-dione, represents a potent and selective 5-HT1A receptor agonist with high efficacy and the potential to regulate anxiety disorders. Herein, we report a method to retro-synthesize eptapirone free base. The compound consists of heterocyclic aromatic portion and aliphatic portion, and the synthetic route consisted of a total of nine steps with an overall yield of 8.8% starting from the commercially available materials. The key steps in the synthetic method involved: (1) using sodium hydroxide and ethylene glycol as solvent resulted in a better cyclization and yield (61.6%) of 1,2,4-triazine-3,5(2H,4H)-dione; (2) an acceptable yield (63.1%) of 4-tert-butyl(pyrimidin-2-yl)piperazine-1-carboxylate was obtained under an optimized conditions of using triethylamine as a base, ethanol as a solvent, and a reaction temperature of 50?°C for 16?h with non-metal catalysis and less byproducts; (3) the reaction step of eptapirone could get a better yield (49.6%) with an optimized condition of potassium carbonate as a base, acetonitrile as a solvent, NaI as a catalyst, and a reaction temperature of 50?°C for 12?h by nucleophilic substitution reaction. The main advantages of this route were an acceptable product purity, the commercial availability of all starting materials and the absence of high temperature, high pressure and noble metal catalysts, which could result in more feasible commercial applications.
Full synthesis method of eptapirone
-
Paragraph 0089; 0126; 0127; 0128; 0136, (2018/09/12)
The invention discloses a full synthesis method of eptapirone. The full synthesis method comprises the following steps: (1) taking aminourea hydrochloride and trichloracetic aldehyde as raw materialsand carrying out a series of reaction to obtain 2-[2-(aminocarbonyl)hydrazono](CD-1); (2) synthesizing 6-azauracil(CD-2) by the 2-[2-(aminocarbonyl)hydrazono] under the action of sodium hydroxide; (3)taking the 6-azauracil and acetic anhydride to react to obtain 2-acetyl-2H-[1,2,4]triazine-3,5(2H,4H)-diketone(CD3); (4) taking the 2-acetyl-2H-[1,2,4]triazine-3,5(2H,4H)-diketone to react to obtain3-methyl-6-azauracil(CD-4); (5) taking the 3-methyl-6-azauracil to react to obtain 2-(4-chlorobutyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)-diketone(CD-5); (6) taking 2-bromopyrimidine, 1-Boc-piperazine and triethylamine to react to obtain 4-(pyrimidine-2-yl)piperazine-1-tert-butyl formate(CD-6); furthermore, reacting to obtain 2-(1-piperazinyl)pyrimidine hydrochloride (1 to 1)(CD-7); (7) taking the 2-(4-chlorobutyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)-diketone in step (5) to react with the 2-(1-piperazinyl)pyrimidine hydrochloride in step (6) to obtain the eptapirone(CD-8). The product disclosed by the invention is high in purity and yield and is suitable for industrialized production.
A 1 - (2 - pyrimidinyl) piperazine hydrochloride preparation method (by machine translation)
-
Paragraph 0015-0016; 0017-0018; 0019-0020; 0021-0022, (2017/09/12)
The present invention discloses a process for the preparation of 1 - (2 - pyrimidinyl) piperazine hydrochloride of the new method. N - Boc - piperazine in alkaline conditions with the cartridge 2 - chloro pyrimidine by condensation reaction to obtain 1 - (2 - pyrimidinyl) - 4 - Boc - piperazine, then hydrolyzed under acidic conditions to obtain 1 - (2 - pyrimidine) hydrochloride. The reaction process is simple, less impurities, it is convenient to store the product, low cost, and is suitable for industrial production. (by machine translation)
Iridium-catalyzed C-H borylation of heteroarenes: Scope, regioselectivity, application to late-stage functionalization, and mechanism
Larsen, Matthew A.,Hartwig, John F.
, p. 4287 - 4299 (2014/04/03)
A study on the iridium-catalyzed C-H borylation of heteroarenes is reported. Several heteroarenes containing multiple heteroatoms were found to be amenable to C-H borylation catalyzed by the combination of an iridium(I) precursor and tetramethylphenanthroline. The investigations of the scope of the reaction led to the development of powerful rules for predicting the regioselectivity of borylation, foremost of which is that borylation occurs distal to nitrogen atoms. One-pot functionalizations are reported of the heteroaryl boronate esters formed in situ, demonstrating the usefulness of the reported methodology for the synthesis of complex heteroaryl structures. Application of this methodology to the synthesis and late-stage functionalization of biologically active compounds is also demonstrated. Mechanistic studies show that basic heteroarenes can bind to the catalyst and alter the resting state from the olefin-bound complex observed during arene borylation to a species containing a bound heteroarene, leading to catalyst deactivation. Studies on the origins of the observed regioselectivity show that borylation occurs distal to N-H bonds due to rapid N-H borylation, creating an unfavorable steric environment for borylation adjacent to these bonds. Computational studies and mechanistic studies show that the lack of observable borylation of C-H bonds adjacent to basic nitrogen is not the result of coordination to a bulky Lewis acid prior to C-H activation, but the combination of a higher-energy pathway for the borylation of these bonds relative to other C-H bonds and the instability of the products formed from borylation adjacent to basic nitrogen.
THERAPEUTIC COMPOUNDS AND COMPOSITIONS
-
Page/Page column 27, (2011/01/05)
Compounds and compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.
ACETYLENE DERIVATIVES AS STEAROYL COA DESATURASE INHIBITORS
-
Page/Page column 54, (2008/12/05)
The present invention provides Stearoyl CoA Desaturase (SCD) inhibitors, hi particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by Stearoyl CoA Desaturase 1 (SCD 1) inhibitors. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by Stearoyl CoA Desaturase (SCD) inhibitors.
Molecular iodine-catalyzed facile procedure for N-Boc protection of amines
Varala, Ravi,Nuvula, Sreelatha,Adapa, Srinivas R.
, p. 8283 - 8286 (2007/10/03)
An efficient and practical protocol for the protection of various structurally and electronically divergent aryl and aliphatic amines using (Boc)2O in the presence of a catalytic amount of molecular iodine (10 mol%) under solvent-free conditions at ambient temperature is presented.
Parallel synthesis of N-arylpiperazines using polymer-assisted reactions
Duncton, Matthew A. J.,Roffey, Jonathan R. A.,Hamlyn, Richard J.,Adams, David R.
, p. 2549 - 2552 (2007/10/03)
A series of N-arylpiperazines were prepared in a parallel fashion using palladium-catalyzed cross-coupling, or nucleophilic aromatic displacement chemistries, and polymer-assisted sequestration and purification techniques as key steps.
