150-59-4Relevant articles and documents
Design and synthesis of alverine-based ionic liquids to improve drug water solubility
Fernández-Stefanuto,Esteiro,Santiago,Moreno,Palomar,Tojo
, p. 20428 - 20433 (2020)
Alverine [3-phenyl-N-(3-phenylpropyl)-N-ethylpropan-1-amine] is a widely known smooth muscle relaxant used to relieve cramps or spasms of the stomach and intestines. As a free base, alverine is a liquid practically insoluble in water while its commercialized form, alverine citrate, is a white solid that can form different crystalline forms. With the aim of increasing alverine water solubility while avoiding polymorphs, in this work, the design, total synthesis, and characterization of a series of new ionic liquids incorporating alverine as the cation were carried out. The selection of the most suitable anions for the active pharmaceutical ingredient-based ionic liquids (API-ILs) was performed calculating the ionic liquid solubility in water by using a priori the COSMO-RS computational tool. The computational analysis of the intermolecular interactions between water and the API-ILs allowed understanding the water solubility of these systems. All the new salts were found to be ionic liquids and their water solubility was shown to be significantly increased compared with the free drug alverine. The highest value was obtained for alverinium tosylate, with a value of 38.10 mg mL-1, 39937-fold higher than that of alverine. Compared to the commercialized drug alverine citrate, a slight increase in water-solubility was observed in all cases. This journal is
Photocatalytic Water-Splitting Coupled with Alkanol Oxidation for Selective N-alkylation Reactions over Carbon Nitride
Xu, Yangsen,Zhang, Zhaofei,Qiu, Chuntian,Chen, Shaoqin,Ling, Xiang,Su, Chenliang
, p. 582 - 589 (2020/12/09)
Photocatalytic water splitting technology (PWST) enables the direct use of water as appealing “liquid hydrogen source” for transfer hydrogenation reactions. Currently, the development of PWST-based transfer hydrogenations is still in an embryonic stage. Previous reports generally centered on the rational utilization of the in situ generated H-source (electrons) for hydrogenations, in which photogenerated holes were quenched by sacrificial reagents. Herein, the fully-utilization of the liquid H-source and holes during water splitting is presented for photo-reductive N-alkylation of nitro-aromatic compounds. In this integrate system, H-species in situ generated from water splitting were designed for nitroarenes reduction to produce amines, while alkanols were oxidized by holes for cascade alkylating of anilines as well as the generated secondary amines. More than 50 examples achieved with a broad range scope validate the universal applicability of this mild and sustainable coupling approach. The synthetic utility of this protocol was further demonstrated by the synthesis of existing pharmaceuticals via selective N-alkylation of amines. This strategy based on the sustainable water splitting technology highlights a significant and promising route for selective synthesis of valuable N-alkylated fine chemicals and pharmaceuticals from nitroarenes and amines with water and alkanols.
Method for reducing residues of N-ethyl-3-phenylpropylamine in alverine
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Paragraph 0055; 0060; 0061, (2018/11/03)
The invention relates to a method for reducing residues of N-ethyl-3-phenylpropylamine in alverine, and belongs to an impurity removal method of compounds. The method comprises the following steps: dissolving an intermediate alverine crude product containing impurity N-ethyl-3-phenylpropylamine into a water-insoluble organic solvent, extracting an organic layer by using an aqueous solution with appropriate pH and discarding a water layer; drying and filtering the organic layer, decompressing and evaporating the solvent to dryness. According to the method disclosed by the invention, a clear, simple and reliable solution to the residues of the N-ethyl-3-phenylpropylamine in the intermediate alverine is provided for the first time, so that the subsequently produced crude drug citric acid alverine has higher quality and the residue amount does not exceed 0.15 percent. The method has the advantages of simplicity, feasibility, low cost, few wastes and suitability for industrial popularization.
