82717-96-2Relevant articles and documents
Preparation method of N-[1-(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine
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Paragraph 0067; 0074; 0078; 0082; 0086; 0090; 0094; 0098, (2018/07/15)
The invention provides a preparation method of N-[1-(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine. The preparation method comprises the following steps: performing addition reaction on a compound I and a compound II under the action of a first catalyst to obtain an addition product, wherein the first catalyst is selected from a first thiourea compound and/or a urea compound; performing hydrogenation reaction on the addition product to obtain the N-[1-(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine. The first catalyst (the first thiourea compound and/or the urea compound) can be added to the reaction system, the selectivity of the addition reaction is improved and the separation efficiency of the required product in the addition reaction process is improved, so that the yield of the final product N-[1-(S)-ethoxy carbonyl-3-phenyl propyl]-L-alanine is increased. The method has the advantages of being short in synthesis route, simple in aftertreatment, capable of being applied to industrialized production and the like.
Impurity profiling of trandolapril under stress testing: Structure elucidation of by-products and development of degradation pathway
Dendeni,Cimetiere,Amrane,Hamida, N. Ben
, p. 61 - 70 (2013/01/13)
Various regulatory authorities like International Conference on Harmonization (ICH), US Food and Drug Administration, Canadian Drug and Health Agency are emphasizing on the purity requirements and the identification of impurities in active pharmaceutical drugs. Qualification of the impurities is the process of acquiring and evaluating data that establishes biological safety of an individual impurity; thus, revealing the need and scope of impurity profiling of drugs in pharmaceutical research. As no stability-indicating method is available for identification of degradation products of trandolapril, a new angiotensin converting enzyme inhibitor (ACEI), under stress testing, the development of an accurate method is needed for quantification and qualification of degradation products. Ultra high performance liquid chromatography (UPLC) coupled to electrospray tandem mass spectrometry was used for the rapid and simultaneous analysis of trandolapril and its degradation products. Chromatographic separation was achieved in less than 4 min, with improved peak resolution and sensitivity. Thanks to this method, the kinetics of trandolapril degradation under various operating conditions and the characterization of the structure of the by-products formed during stress testing have been determined. Thereafter, a mechanism of trandolapril degradation in acid and neutral conditions, including all the identified products, was then proposed.
Process for preparing pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acids
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Example 1, (2008/06/13)
There is provided a process for preparing a pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid which comprises condensing an amino acid and N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine.N-carboxyanhydride under basic condition, carrying out decarboxylation under between neutral and acidic condition to obtain N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid, and forming a pharmacologically acceptable salt thereof, wherein the production of a by-product (3): is suppressed by carrying out in an aqueous liquid a series of operations till formation of the pharmacologically acceptable salt or till isolation of the pharmacologically acceptable salt. The present invention enables to prepare the pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid having high quality, in a commercial scale with high yield and economical efficiency.