68432-92-8Relevant academic research and scientific papers
Cyano ketoprofen synthesis process
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Paragraph 0010; 0012; 0014, (2020/09/30)
The invention relates to a cyano ketoprofen synthesis process, which comprises the following steps: acylating chlorination, chlorination, esterification, cyaniding, distillation, methylation, hydrolysis, refining, acylation Friedel-Crafts ice precipitation distillation, and refining to finally obtain the cyano ketoprofen finished product. According to the cyano ketoprofen synthesis process, the synthesized product is low in cost, by acylating chlorination, esterification, cyaniding, methylation, Friedel-Crafts acylation and hydrolysis reaction, the product is prepared from m-toluic acid as a starting material, the process and the operation process are simplified, the safety and the reliability are provided, the wastewater and the waste gas generated during the reaction process are recycled, and the residue generated in the kettle is subjected to hazardous waste treatment, such that the environment is protected, the industrial production is promoted, the production efficiency is improved, and the purity of the synthesized finished product achieves 99% or more.
Radical cyanomethylation via vinyl azide cascade-fragmentation
Donald, James R.,Berrell, Sophie L.
, p. 5832 - 5836 (2019/06/17)
Herein, a novel methodology for radical cyanomethylation is described. The process is initiated by radical addition to the vinyl azide reagent 3-azido-2-methylbut-3-en-2-ol which triggers a cascade-fragmentation mechanism driven by the loss of dinitrogen and the stabilised 2-hydroxypropyl radical, ultimately effecting cyanomethylation. Cyanomethyl groups can be efficiently introduced into a range of substrates via trapping of α-carbonyl, heterobenzylic, alkyl, sulfonyl and aryl radicals, generated from a variety of functional groups under both photoredox catalysis and non-catalytic conditions. The value of this approach is exemplified by the late-stage cyanomethylation of pharmaceuticals.
Palladium-Catalyzed, ortho-Selective C-H Halogenation of Benzyl Nitriles, Aryl Weinreb Amides, and Anilides
Das, Riki,Kapur, Manmohan
, p. 1114 - 1126 (2018/06/18)
A palladium-catalyzed, ortho-selective C-H halogenation methodology is reported herein. The highlight of the work is the highly selective C(sp2)-H functionalization of benzyl nitriles in the presence of activated C(sp3)-H bond, which results in good yields of the halogenated products with excellent regioselectivity. Along with benzyl nitriles, aryl Weinreb amides and anilides have been evaluated for the transformation using aprotic conditions. Mechanistic studies yield interesting aspects with respect to the pathway of the reaction and the directing group abilities.
Preparation method of m-cyanomethyl methyl benzoate
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, (2017/08/30)
The invention discloses a preparation method of m-cyanomethyl methyl benzoate. According to the method, m-bromobenzoic acid is used as a starting raw material; the m-bromine methyl methyl benzoate is prepared through esterification; m-methoxy formyl phenethyl alcohol is obtained and prepared through Grignard reaction; through oxidization, the m-methoxy formyl phenylacetic acid is prepared; through amidation and dewatering, the m-cyanomethyl methyl benzoate is finally prepared. The preparation method provided by the invention has the advantages that the design is ingenious; the route is novel; the raw materials have low price and can be easily obtained; the process is simple; the implementation is easy; the yield is high; the purity of the obtained final product is high; the quality is high; no dangerous process exists; the extremely toxic substances of cyanides and expensive cyaniding reagents used in the conventional synthesis are avoided; the requirements on the equipment are simple; the production difficulty and the production cost investment are reduced; the industrial production can be favorably realized; the economic benefits are good.
HIGHLY WATER-SOLUBLE SALTS OF A SHORT ACTING PHENYLALKYLAMINE CALCIUM CHANNEL BLOCKER AND USES THEREOF
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Page/Page column 22, (2016/11/02)
The present invention includes surprisingly water-soluble salts of a phenylalkylamine compound that are potent antagonists of L-type calcium channels. Aqueous solutions including salts of the instant invention are formulated for nasal administration and provide a novel therapeutic platform for the treatment of stable angina, migraine, and cardiac arrhythmia, such as paroxysmal supraventricular tachycardia.
BIARYL AMIDE COMPOUNDS AS KINASE INHIBITORS
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Paragraph 0182, (2014/09/29)
The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.
THIENO (2, 3B) PYRAZINE COMPOUNDS AS B-RAF INHIBITORS
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Paragraph 0104, (2013/04/10)
The invention relates to compounds according to general Formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of cancer.
Novel symmetrical ureas as modulators of protein arginine methyl transferases
Fontán, Noelia,García-Domínguez, Patricia,álvarez, Rosana,De Lera, ángel R.
, p. 2056 - 2067 (2013/05/09)
Methylation of histone arginine residues is an epigenetic mark related to gene expression that is implicated in a variety of biological processes and can be reversed by small-molecule modulators of protein arginine methyltransferases (PRMTs). A series of symmetrical ureas, designed as analogues of the known PRMT1 inhibitor AMI-1 have been synthesized using Pd-catalyzed Ar-N amide bond formation processes or carbonylation reactions as key steps. Their inhibitory profile has been characterized. The enzymatic assays showed a weak effect on PRMT1 and PRMT5 activity for most of the compounds. The acyclic urea that exhibited the strongest effect on the inhibition of the PRMT1 activity also showed the greatest effect on the expression of some androgen receptor target genes (TMPRSS2 and FKBP5), which may be related with its enzymatic activity. Surprisingly, AMI-1 behaved as an activator of PRMT5 activity, a result not reported so far.
DISUBSTITUTED MALEIC ANHYDRIDES WITH ALTERED KINETICS OF RING CLOSURE
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Page/Page column 28-29, (2013/02/28)
We describe anhydride compounds suitable for physiologically labile modification of amine- containing molecules. The described anhydrides form reversible linkages having desirable kinetics for in vivo delivery of biologically active molecules. Also described are endosomolytic polymers formed by modification of membrane active polyamines with the described anhydrides.
Rhodium-catalyzed asymmetric hydrogenation of olefins with PhthalaPhos, a new class of chiral supramolecular ligands
Pignataro, Luca,Boghi, Michele,Civera, Monica,Carboni, Stefano,Piarulli, Umberto,Gennari, Cesare
, p. 1383 - 1400 (2012/03/27)
A library of 19 binol-derived chiral monophosphites that contain a phthalic acid diamide group (Phthala- Phos) has been designed and synthesized in four steps. These new ligands were screened in the rhodium-catalyzed enantioselective hydrogenation of prochiral dehydroamino esters and enamides. Several members of the library showed excellent enantioselectivity with methyl 2-acetamido acrylate (6 ligands gave >97% ee), methyl (Z)-2- acetamido cinnamate (6 ligands gave >94% ee), and N-(1-phenylvinyl)acetamide (9 ligands gave >95% ee), whilst only a few representatives afforded high enantioselectivities for challenging and industrially relevant substrates N-(3,4-dihydronaphthalen-1- yl)-acetamide (96% ee in one case) and methyl (E)-2-(acetamidomethyl)-3- phenylacrylate (99% ee in one case). In most cases, the new ligands were more active and more stereoselective than their structurally related monodentate phosphites (which are devoid of functional groups that are capable of hydrogen-bonding interactions). Control experiments and kinetic studies were carried out that allowed us to demonstrate that hydrogen-bonding interactions involving the diamide group of the PhthalaPhos ligands strongly contribute to their outstanding catalytic properties. Computational studies carried out on a rhodium precatalyst and on a conceivable intermediate in the hydrogenation catalytic cycle shed some light on the role played by hydrogen bonding, which is likely to act in a substrate-orientation effect.
