20850-49-1Relevant academic research and scientific papers
Method for synthesizing α - isopropyl -3 and 4 -methoxyacetonitrile
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Paragraph 0005-0006; 0020; 0025-0026; 0027; 0032-0033..., (2021/09/29)
The invention belongs to the technical field of organic synthesis, and particularly discloses a synthesis method α - isopropyl -3 and 4 -methoxyacetonitrile. To 3, 4 - dimethoxyphenyl acetic acid as a raw material, 2 - (3, 4 - dimethoxyphenyl) acetamide is formed through acylation reaction, and 3, 4 -methoxyphenyl acetonitrile are obtained by dehydration, and α - isopropyl -3 and 4 -methoxyacetonitrile are formed by alkylation reaction. The starting materials are cheap and easily available. The method avoids the use of highly toxic crisis reagents, is mild in reaction conditions, simple in post-treatment, short in synthetic route and high in yield.
Enantioselective synthesis of nitriles containing a quaternary carbon center by michael reactions of silyl ketene imines with 1-acrylpyrazoles
Chen, Long,Pu, Maoping,Li, Shiyang,Sang, Xinpeng,Liu, Xiaohua,Wu, Yun-Dong,Feng, Xiaoming
, p. 19091 - 19098 (2021/11/22)
The enantioselective construction of quaternary carbon centers is a marked challenge in asymmetric catalysis research. It is extremely difficult when a chiral catalyst can not distinguish the facial selectivity of the substrate through bond interactions. Here we realized an enantioselective Michael reaction of silyl ketene imines to 1-acrylpyrazoles using a chiral N,N′-dioxide-Co(II) complex. The protocol is highly efficient for the construction of nitrile-, aryl-, and dialkyl-bearing carbon centers and has been successful applied in the divergent synthesis of pharmaceuticals and natural products. The through-space dispersion interactions between unbound silyl ketene imines and the 1-acrylpyrazole-bonded catalyst play a key role in facilitating the reactivity and the enantioselectivity of this process.
A Concise and Modular Three-Step Synthesis of (S)-Verapamil using an Enantioselective Rhodium-Catalyzed Allylic Alkylation Reaction
Evans, P. Andrew,Tom, Mai-Jan,Turnbull, Ben W. H.
, p. 2185 - 2189 (2020/08/26)
A concise and modular asymmetric synthesis of the calcium channel blocker (S)-verapamil is described. This approach employs an enantioselective rhodium-catalyzed allylic alkylation reaction between an α-isopropyl-substituted benzylic nitrile and allyl benzoate to construct the challenging acyclic quaternary stereocenter. The terminal olefin then serves as a convenient synthetic handle for a hydroamination to introduce the phenethylamine moiety, furnishing (S)-verapamil in three steps and 55% overall yield, thus providing the most efficient synthesis of this important pharmaceutical reported to date. Furthermore, given the modular nature of the synthesis, it can be readily modified to prepare structurally related bioactive agents.
Synthesis of Nitrile-Bearing Quaternary Centers by an Equilibrium-Driven Transnitrilation and Anion-Relay Strategy
Alazet, Sébastien,West, Michael S.,Patel, Purvish,Rousseaux, Sophie A. L.
supporting information, p. 10300 - 10304 (2019/07/04)
The efficient preparation of nitrile-containing building blocks is of interest due to their utility as synthetic intermediates and their prevalence in pharmaceuticals. As a result, significant efforts have been made to develop methods to access these motifs which rely on safer and non-toxic sources of CN. Herein, we report that 2-methyl-2-phenylpropanenitrile is an efficient, non-toxic, electrophilic CN source for the synthesis of nitrile-bearing quaternary centers by a thermodynamic transnitrilation and anion-relay strategy. This one-pot process leads to nitrile products resulting from the gem-difunctionalization of alkyl lithium reagents.
HIGHLY WATER-SOLUBLE SALTS OF A SHORT ACTING PHENYLALKYLAMINE CALCIUM CHANNEL BLOCKER AND USES THEREOF
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Page/Page column 21-22, (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.
Indium Tribromide Catalyzed Coupling Reaction of Enol Ethers with Silyl Ketene Imines toward the Synthesis of β,γ-Unsaturated Nitriles
Nishimoto, Yoshihiro,Nishimura, Takashi,Yasuda, Makoto
supporting information, p. 18301 - 18308 (2015/12/24)
Herein, a coupling reaction of enol ethers with silyl ketene imines in the presence of catalytic amounts of InBr3 and Me3SiBr is described. Kinetic studies have revealed that an indium catalyst and Me3SiBr accelerated the coupling process and the regeneration of the catalyst, respectively. Various types of enol ethers and silyl ketene imines are applicable. In addition, a formal synthesis of verapamil was achieved by using this novel coupling reaction. Let's get together: The coupling reaction of enol ethers with silyl ketene imines in the presence of a catalytic amount of InBr3 and Me3SiBr is shown (see scheme, TBS=tert-butyl dimethylsilyl). Kinetic studies revealed that an indium salt and Me3SiBr accelerated the coupling process and the regeneration of the catalyst. Several enol ethers and silyl ketene imines are applicable to this strategy.
Rational Design and Synthesis of Thioridazine Analogues as Enhancers of the Antituberculosis Therapy
Pieroni, Marco,Machado, Diana,Azzali, Elisa,Santos Costa, Sofia,Couto, Isabel,Costantino, Gabriele,Viveiros, Miguel
supporting information, p. 5842 - 5853 (2015/08/24)
Tuberculosis, caused by Mycobacterium tuberculosis, is still one of the leading infectious diseases globally. Therefore, novel approaches are needed to face this disease. Efflux pumps are known to contribute to the emergence of M. tuberculosis drug resistance. Thioridazine has shown good anti-TB properties both in vitro and in vivo, likely due to its capacity to inhibit efflux mechanisms. Here we report the design and synthesis of a number of putative efflux inhibitors inspired by the structure of thioridazine. Compounds were evaluated for their in vitro and ex vivo activity against M. tuberculosis H37Rv. Compared to the parent molecule, some of the compounds synthesized showed higher efflux inhibitory capacity, less cytotoxicity, and a remarkable synergistic effect with anti-TB drugs both in vitro and in human macrophages, demonstrating their potential to be used as coadjuvants for the treatment of tuberculosis.
Design, synthesis and evaluation of 9-hydroxy-7H-furo [3,2-g]chromen-7-one derivatives as new potential vasodilatory agents
Wang, Cheng,Wang, Tao,Zhou, Nan,Pan, Xiao-Yan,He, Huai-Zhen
, p. 304 - 311 (2014/02/14)
Two new 9-hydroxy-7H-furo[3,2-g]chromen-7-one derivatives were designed, synthesized and evaluated for their in vitro vasodilatory activity. The structures of two compounds were elucidated by infrared, 1H NMR, and mass spectral data. The invitro pharmacological evaluation indicated that both of them possessed well vasodilatory activity compared with imperatorin. The molecule docking also showed two target compounds docked well with L-calcium channel (PDB code: 3G43). The result suggested that they would be potential vasodilatory agents for hypertension.
Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c
Singh, Kawaljit,Kumar, Malkeet,Pavadai, Elumalai,Naran, Krupa,Warner, Digby F.,Ruminski, Peter G.,Chibale, Kelly
supporting information, p. 2985 - 2990 (2014/06/24)
New verapamil analogues were synthesized and their inhibitory activities against Mycobacterium tuberculosis H37Rv determined in vitro alone and in combination with rifampicin (RIF). Some analogues showed comparable activity to verapamil and exhibited better synergies with RIF. Molecular docking studies of the binding sites of Rv1258c, a M. tuberculosis efflux protein previously implicated in intrinsic resistance to RIF, suggested a potential rationale for the superior synergistic interactions observed with some analogues.
Facile preparation of α-aryl nitriles by direct cyanation of alcohols with TMSCN under the catalysis of InX3
Chen, Gang,Wang, Zheng,Wu, Jiang,Ding, Kuiling
supporting information; experimental part, p. 4573 - 4576 (2009/05/07)
(Chemical Equation Presented) A convenient and efficient synthesis of α-aryl nitrites was developed by direct cyanation of alcohols with TMSCN under the catalysis of Lewis acid. Using 5-10 mol % of InBr3 as the catalyst, a variety of benzylic alcohols can be converted to the corresponding nitriles in 5-30 min with yields of 46-99%.
