1086026-31-4Relevant articles and documents
AN IMPROVED PROCESS FOR THE SYNTHESIS OF IVABRADINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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, (2019/11/12)
: Disclosed herein is an improved process for the preparation of Ivabradine and pharmaceutically acceptable salts thereof. The invention more particularly disclosesthe synthesis of key intermediates viz.,(S)-N-[(4,5-dimethoxybenzocydobut-l-yl)-methyl]-N- (methyl)amine hydrochloride of Formula-II and 3-(3-Iodopropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzapin-2-one of Formula-III, and its use in industrial synthesis of Ivabradine and pharmaceutically acceptable salts thereof.
Dehydrogenated ivabradine oxalate preparation method
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Paragraph 0064; 0065; 0066, (2018/04/02)
The invention relates to the technical field of organic chemical synthesis, in particular to a dehydrogenated ivabradine oxalate preparation method and aims to solve technical problems of high impurity content and complexity in subsequent treatment in a dehydrogenated ivabradine oxalate synthesis process. The technical scheme for implementation includes that a synthetic route includes: adding a compound (III) or salts thereof and a compound (II) into a nonpolar solvent, mixing, adding inorganic base, iodine compounds and a phase transfer catalyst, and heating for stirring reaction to obtain acompound (I); adding oxalic acid ethanol solution for salification, so that high-purity dehydrogenated ivabradine oxalate is obtained. The dehydrogenated ivabradine oxalate preparation method has advantages that impurity (A) content can be evidently reduced, reaction liquid purity can be remarkably improved while product yield is increased, an aftertreatment process is simplified, complicated operations of distillation or repeated extraction in use of polar solvents are avoided, and the method is more suitable for industrialization.
Dehydrogenated ivabradine synthesizing method
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Paragraph 0054; 0055; 0056, (2018/04/02)
The invention relates to the technical field of organic chemical synthesis, in particular to a dehydrogenated ivabradine synthesizing method and aims to solve technical problems of high impurity content and complexity in subsequent treatment in a dehydrogenated ivabradine synthesis process. The technical scheme for implementation includes that a synthetic route includes: adding a compound (III) orsalts thereof and a compound (II) into a nonpolar solvent, mixing, adding inorganic base, iodine compounds and a phase transfer catalyst, and heating for stirring reaction to obtain a compound (I). The dehydrogenated ivabradine synthesizing method has advantages that impurity (A) content can be evidently reduced, reaction liquid purity can be remarkably improved while product yield is increased,an aftertreatment process is simplified, complicated operations of distillation or repeated extraction in use of polar solvents are avoided, and the method is more suitable for industrialization.
A high-purity hydrochloric acid Ivabradine preparation method (by machine translation)
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Paragraph 0039; 0041-0045; 0049; 0051-0056, (2018/09/11)
The invention discloses a high-purity hydrochloric acid Ivabradine preparation method, the method after the nucleophilic substitution, catalytic hydrogenation, into the hydrochloric acid salt of three-step reaction, the preparation of the hydrochloride of ivabradine, wherein the use of bicarbonate solution to wash the dehydrogenation Ivabradine solution to remove most of the un-reacted compound II, to avoid a column chromatography operation, the operation is simple; at the same time, the way using atmospheric pressure of hydrogenation, does not need to use high-pressure hydrogenation cauldron, also non-blocking condenser risk, safe operation; the resulting salts are acid Ivabradine purity to be 99.8%, most large [...]0.10%, does not need to re-refining can achieve the standard of the raw material, the reaction route is as follows. (by machine translation)
Ivabradine and its intermediate preparation method
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Paragraph 0068-0069; 0073-0076, (2018/11/03)
The invention provides a preparation method for ivabradine and an intermediate thereof dehydrogenated ivabradine. The preparation method of the dehydrogenated ivabradine comprises: step a1, enabling a compound shown as a formula II and a compound shown as a formula III to have a nucleophilic substitution reaction in a polar aprotic solvent in the presence of an acid binding agent and a composite phase-transfer catalyst to generate dehydrogenated ivabradine; and step b1, performing separation and purification on dehydrogenated ivabradine obtained in the step a1. The composite phase-transfer catalyst is composed of a quaternary ammonium salt phase-transfer catalyst and a polyether phase-transfer catalyst with the mass ratio of 1-10:1, and X in the formula II is selected from Cl, Br, I, sulfonyloxy, methane sulfonyloxy, benzene sulfonyloxy, p-methylbenzene sulfonyloxy, o-methylbenzene sulfonyloxy or m-methylbenzene sulfonyloxy. The method is capable of substantially shortening the time of nucleophilic substitution reaction, improving product purity, avoiding a column chromatography process and reducing production cost.
A group of synthetic Ivabradine intermediate compound and use thereof
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Paragraph 0054, (2017/10/06)
The invention provides a set of intermediate compounds used for synthesis of Ivabradine and a preparation method thereof, and also provides a method used for synthesizing Ivabradine from the intermediate compounds. According to the method, the set of intermediate compounds are subjected to a plurality of N alkylation or N acylation so as to obtain a compound IV; and Ivabradine is directly synthesized from the compound IV. The method is short in synthesis route; raw materials are simple and easily available; reaction sequence is reasonable; operation is simple and high in efficiency; the method is green and friendly to the environment; synthesis difficulty of Ivabradine is reduced greatly; cost is low; product yield is high; and the method is suitable for industrialization production.
Ivabradine and preparation method of a pharmaceutically acceptable salt thereof
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Paragraph 0011; 0022-0023, (2017/08/25)
The invention discloses a preparation method for ivabradine. The method includes: in the presence of a noble metal catalyst and a hydrogen transfer reagent, subjecting 3-3{-[{[(7S)-3, 4-dimethoxy benzocyclobutene-7-]methyl}(methyl)amino-propyl]- 7, 8-dimethoxy-1, 3-dihydro-2-hydro-3-benzoazepine-2-one to hydrogen transfer reaction, and after complete reaction, conducting aftertreatment to obtain the ivabradine. The method provided by the invention avoids strict requirements for equipment in hydrogenation reaction, also effectively reduces side effect, and increases the reaction yield.
PROCESS FOR THE PREPARATION OF BENZAZEPINE-2-ONE DERIVATIVE
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, (2017/09/05)
The present, invention relates to a cost effective, environment friendly industrially viable process for the preparation of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepine-2-one, an intermediate used in the preparation of ivabradine, without using acid chloride intermediate and condensing agent.
PROCESS FOR THE SYNTHESIS OF (2E)-3-(3,4-DIMETHOXYPHENYL)PROP-2-ENENITRILE, AND APPLICATION IN THE SYNTHESIS OF IVABRADINE AND ADDITION SALTS THEREOF WITH A PHARMACEUTICALLY ACCEPTABLE ACID
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, (2014/05/20)
Process for the synthesis of the compound of formula (I): Application in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof.
PROCESS FOR THE SYNTHESIS OF 3-(2-BROMO-4,5-DIMETHOXYPHENYL)PROPANENITRILE, AND APPLICATION IN THE SYNTHESIS OF IVABRADINE AND ADDITION SALTS THEREOF WITH A PHARMACEUTICALLY ACCEPTABLE ACID
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, (2014/06/24)
Process for the synthesis of the compound of formula (I): Application in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof.
