654-70-6Relevant academic research and scientific papers
High Turnover Pd/C Catalyst for Nitro Group Reductions in Water. One-Pot Sequences and Syntheses of Pharmaceutical Intermediates
Gallou, Fabrice,Li, Xiaohan,Lipshutz, Bruce H.,Takale, Balaram S.,Thakore, Ruchita R.
supporting information, p. 8114 - 8118 (2021/10/25)
Commercially available Pd/C can be used as a catalyst for nitro group reductions with only 0.4 mol % Pd loading. The reaction can be performed using either silane as a transfer hydrogenating agent or simply a hydrogen balloon (μ1 atm pressure). With this technology, a series of nitro compounds was reduced to the desired amines in high chemical yields. Both the catalyst and surfactant were recycled several times without loss of reactivity.
Late-stage Pd-catalyzed Cyanations of Aryl/Heteroaryl Halides in Aqueous Micellar Media
Thakore, Ruchita R.,Takale, Balaram S.,Singhania, Vani,Gallou, Fabrice,Lipshutz, Bruce H.
, p. 212 - 216 (2020/12/01)
New technology is described that enables late stage ppm Pd-catalyzed cyanations of highly complex molecules, as well as a wide variety of aryl and heteroaryl halides possessing sensitive functional groups. These reactions are efficient in water containing nanomicelles, formed from a commercially available and inexpensive surfactant. The implications for advancing drug synthesis and discovery are apparent.
Preparation method of 4-amino-2-trifluoromethyl benzonitrile
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Paragraph 0036; 0044-0046; 0047; 0053-0054, (2020/05/14)
The invention relates to the technical field of chemical engineering, in particular to a preparation method of 4-amino-2-trifluoromethyl benzonitrile, which comprises the following steps: after 2-bromo-5-fluorobenzotrifluoride is subjected to a Grignard reaction, feeding carbon dioxide, and hydrolyzing to obtain 4-fluoro-2-trifluoromethyl benzoic acid; adding the 4-fluoro-2-trifluoromethyl benzoicacid into a pressure kettle, feeding liquid ammonia, and reacting under the action of a catalyst to generate 4-amino-2-trifluoromethyl benzamide; heating and dehydrating the 4-amino-2-trifluoromethylbenzamide with a dehydrating agent to generate the 4-amino-2-trifluoromethyl benzonitrile. According to the preparation method, highly toxic cuprous cyanide is not adopted, so that the safety risk ofproduction is reduced, and three wastes do not contain cyanide ions or a large amount of copper ions, are easier to treat and have small harm to the environment.
Method for synthesizing 4- amino -2- trifluoromethyl cyanobenzene
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Paragraph 0023-0028, (2020/03/16)
The method 4 - comprises the following steps, dissolving m-aminotrifluorotoluene in a solvent :S1, and adding ethyl formate, into toluene, and adding acetic acid, to reflux to obtain 4 - amino-2-trifluoromethylbenzonitrile ;S2, and adding the 4 - amino - 2 2-trifluoromethyl cyanobenzaldehyde, into toluene through reflux reaction, to obtain 4 - amino - 2 2-trifluoromethyl cyanobenzonitrile in a ratio. The invention discloses S1 amino- 2 2-trifluoromethyl cyanobenzonitrile in the following processing step: Step 1:1-10, The reaction is mild and no special equipment 8%-10%, is required to be used, 50%-60%. The method comprises the following steps of: synthesizing ethyl formate and refluxing acetic acid; and synthesizing ethyl formate by adding the methyl formate to toluene and refluxing the acetic acid ethyl ester to prepare, amino. 2 2-trifluoromethylbenzonitrile.
Catalytic Cyanation Using CO2 and NH3
Wang, Hua,Dong, Yanan,Zheng, Chaonan,Sandoval, Christian A.,Wang, Xue,Makha, Mohamed,Li, Yuehui
supporting information, p. 2883 - 2893 (2019/01/05)
Li and co-workers describe the catalytic cyanation of organic halides with CO2 and NH3. In the presence of Cu2O/DABCO as the catalyst, a variety of aromatic bromides and iodides were transformed to the desired nitrile products with broad functional-group tolerance. Both 13C- and/or 15N-labeled nitriles were obtained conveniently with appropriately isotope-labeled CO2 and NH3. Construction of functionalized chemical compounds from small molecules in a highly selective and efficient manner is crucial for sustainable development. The chemical-based manufacturing sector of the future should aim to produce chemicals from very simple and abundant resources, just as nature uses CO2 and N2 to generate sugars, amino acids, and so forth. In practice, however, the utilization of CO2 for the generation of industrial products, such as drugs and related intermediates, still remains a major challenge. Here, we describe the facile cyanide-free production of high-value nitriles with CO2 and NH3 as the sole sources of carbon and nitrogen, respectively. This practical and catalytic methodology provides a unique strategy for the utilization of small molecules for sustainable and cost-effective applications. Selective cyanation of aryl halides was achieved with CO2 and NH3 as the only sources of carbon and nitrogen, respectively. In the presence of Cu catalysts under low pressure (3 atm), a variety of aromatic iodides and bromides were transformed to the desired nitrile products without the use of toxic metal cyanides. Notably, olefins, esters, amides, alcohols, and amino groups were tolerated. Mechanistic studies suggest that Cu(III)-aryl insertion by isocyanate intermediates is involved. [13C,15N]-labeled nitriles were conveniently accessible from the respective isotope-labeled CO2 and NH3 via this methodology.
Cyaniding method for preparing nitrile compound
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Paragraph 0116-0118, (2018/05/30)
The invention provides a cyaniding method for preparing a nitrile compound. Organic halide or pseudohalide, CO2 and NH3 which are low in price and are easily obtained and a reducing agent react, a selective cyaniding reaction is conducted in the presence of a transition metal catalyst, and the target product namely organic the nitrile compound is obtained. According to the cyaniding method for preparing the nitrile compound, a new reaction route is used, through a CO2 and NH3 reaction of metal catalysis, dehalogenation cyaniding or quasi halide cyaniding of halide or pseudohalide is directly achieved through a one-pot method, the problem is solved that a traditional cyanation reaction needs equivalent toxic cyanide, a new direct and convenient method for preparing isotope-labeled nitrile compounds is provided at the same time, and the method can be applied to medicine, tracing, biology and medicine research and development.
Design and development of oxobenzimidazoles as novel androgen receptor antagonists
Elancheran,Saravanan,Choudhury, Bhaswati,Divakar,Kabilan,Ramanathan,Das, Babulal,Devi,Kotoky, Jibon
, p. 539 - 552 (2016/03/08)
Antiandrogens are a novel class of anticancer agents that inhibit cancer cell proliferation and induce apoptosis in various cell lines. To find the lead compound from the oxobenzimidazole derivatives, receptor-ligand docking studies were initially performed using Schr?dinger software. The best fit molecules were synthesized and characterized through IR, 1H-NMR, 13C-NMR and HRMS analyses. The structure of compound (9b) was further confirmed by single-crystal XRD analysis. The cell viability of the compounds was determined by MTT assay to find IC50 values against prostate cancer and breast cancer cell lines (PC-3, LNCaP, MCF-7 and MDA-MB-231). The ADME/T property studies were performed to rationalize the inhibitory properties of these compounds. It can be concluded from the study that 9b is the most active compound from the series against PC-3 and LNCaP cell lines.
Synthesis and structure-activity relationships of the first ferrocenyl-aryl-hydantoin derivatives of the nonsteroidal antiandrogen nilutamide
Payen, Olivier,Top, Siden,Vessières, Anne,Brulé, Emilie,Plamont, Marie-Aude,McGlinchey, Michael J.,Müller-Bunz, Helge,Jaouen, Gérard
, p. 1791 - 1799 (2008/09/20)
We present here the first synthesis of organometallic complexes derived from the nonsteroidal antiandrogen nilutamide, bearing a ferrocenyl substituent at position N(1) or at C(5) of the hydantoin ring; for comparison, we also describe the C(5) p-anisyl organic analogue. All of these complexes retain a modest affinity for the androgen receptor. The N-substituted complexes show a weak or moderate antiproliferative effect (IC50 around 68 μM) on hormone-dependent and -independent prostate cancer cells, while the C(5)-substituted compounds exhibit toxicity levels 10 times higher (IC 50 around 5.4 μM). This strong antiproliferative effect is probably due to a structural effect linked to the aromatic character of the ferrocene rather than to its organometallic feature. In addition, it seems connected to a cytotoxic effect rather than an antihormonal one. These results open the way toward a new family of molecules that are active against both hormone-dependent and hormone-independent prostate cancer cells.
Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators
Hamann, Lawrence G.,Manfredi, Mark C.,Sun, Chongqing,Krystek Jr., Stanley R.,Huang, Yanting,Bi, Yingzhi,Augeri, David J.,Wang, Tammy,Zou, Yan,Betebenner, David. A.,Fura, Aberra,Seethala, Ramakrishna,Golla, Rajasree,Kuhns, Joyce E.,Lupisella, John A.,Darienzo, Celia J.,Custer, Laura L.,Price, Jennifer L.,Johnson, James M.,Biller, Scott A.,Zahler, Robert,Ostrowski, Jacek
, p. 1860 - 1864 (2008/02/04)
Pharmacokinetic studies in cynomolgus monkeys with a novel prototype selective androgen receptor modulator revealed trace amounts of an aniline fragment released through hydrolytic metabolism. This aniline fragment was determined to be mutagenic in an Ames assay. Subsequent concurrent optimization for target activity and avoidance of mutagenicity led to the identification of a pharmacologically superior clinical candidate without mutagenic potential.
Process for producing trifluoromethylbenzylamines
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, (2008/06/13)
The invention relates to a process for producing a trifluotomethylbenzylamine represented by the following general formula (1), 1where each R independently represents a halogen selected from the group consisting of fluorine, chlorine, bromine and iodine, an alkyl group having a carbon atom number of 1-4, an alkoxy group having a carbon atom number of 1-4, an amino group, a hydroxyl group or a trifluoromethyl group, and n represents an integer from 0 to 4. The process includes hydrogenating a trifluoromethylbenzonitrile by hydrogen in an organic solvent in the presence of ammonia and a catalyst containing a platinum group element. This trifluoromethylbenzonitrile is represented by the following general formula (2), 2where R and n are defined as above. With this process, it is possible to obtain the trifluoromethylbenzylamine at an extremely high yield.
