- 2 - Bromo 2 - (2 - fluorophenyl) ethanone preparation of cyclopropyl (by machine translation)
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The invention belongs to the technical field of medicines and particularly relates to a preparation method of a medicine intermediate, and more particularly relates to a preparation method of a prasugrel intermediate cyclopropyl-2-bromo-2-(2-fluorophenyl) ethanone. The preparation method comprises the following steps: carrying out reaction on 2-fluorophenylacetate and cyclopropane carbonyl chloride to prepare cyclopropyl-2-(2-fluorophenyl) ethanone; and then, carrying out halogenating reaction with a bromination reagent to prepare cyclopropyl-2-bromo-2-(2-fluorophenyl) ethanone. The preparation method provided by the invention is carried out under a relatively mild condition, raw materials are easily available, and the obtained product is high in purity and relatively high in yield which reaches over 70%, so that the preparation method is suitable for industrial production.
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- PROCESS FOR THE PREPARATION OF HIGH-PURITY PRASUGREL
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The field of invention relates to a novel process, suitable for industrial scale manufacture, for the preparation of high-purity 5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7- tetrahydrothieno[3,2-c]pyridine-2-yl acetate, prasugrel, of Formula (I). Especially in large-scale production, one of the main causes of piling up the impurities is the use of ether solvents consequently in each step in this procedure ethers are excluded. Avoiding the ethers resulted new conditions for production of intermediates in the different steps of our procedure. Conditions were determined so that each step from the beginning contributes to minimizing the impurity content of the end-product.
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- Method for preparing antithrombotic drug prasugrel intermediate
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The invention discloses a method for preparing an antithrombotic drug prasugrel intermediate. The method includes the following steps that firstly, fluorobenzene makes contact and reacts with 1-bromine-3-alkene-diacetyl to generate 1-(2-fluoro-phenyl)-3-alkene-diacetyl under catalysis of Lewis acid, wherein Lewis acid is stannic chloride; secondly, 1-(2-fluoro-phenyl)-3-alkene-diacetyl generated by 1-bromine-3-alkene-diacetyl reacts with dimethyl phosphite methyl sulfonium or dimethyl sulfoxonium methylide to generate 1-cyclopropyl-2-(2-fluoro-phenyl)-2-ethanone; thirdly, 1-cyclopropyl-2-(2-fluoro-phenyl)-2-ethanone obtained in the second step reacts with a bromide reagent to generate the prasugrel intermediate, namely 1-cyclopropyl-2 bromine-2-(2-fluoro-phenyl)-2-ethanone. A brand-new technology is provided for the prasugrel intermediate and synthesis of the prasugrel intermediate, cost is low, the yield is high, processing is easy, and the method is suitable for industrial production.
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- An anti-platelet drug prasugrel method for the preparation of (by machine translation)
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The invention discloses an anti-platelet drug prasugrel method for preparing, the method includes: 1) the 1 [...] cyclopropyl -2 the [...] (the 2 [...] phenyl) - 2 the and iodine monobromide[...] ethanone and the 1 [...] butyl -3 the imidazolium methyl bromination[...] contact is obtained by reacting the 1 [...] cyclopropyl -2 the- [...] the 2 [...] (the 2 [...] phenyl) - 2 the [...] ethanone; 2) and in iodine under the presence of alkali, the step 1) product with the 2 [...] oxo -2, 4, 5, 6, 7 the [...] the 7a [...] tetrahydro-thieno [3,2 the ??c] pyridine hydrochloride is obtained by reacting the 5 [...] (α-cyclopropane carbonyl -2 the [...] fluorobenzyl) - 2 the [...] oxo -2, 4, 5, 6, 7, 7a-tetrahydro-thieno [3,2 the ??c] pyridine; 3) steps 2) product with triethylamine mixed, then instillment second grade anhydride, shall prasugrel stirring reaction. The method of preparing the prasugrel of this invention high yield, is easy to be treated, is suitable for industrial production. (by machine translation)
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Paragraph 0033; 0034; 0035
(2016/12/16)
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- IMPROVED PROCESS FOR THE PREPARATION OF PRASUGREL AND INTERMEDIATE THEREOF
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The invention relates to an industrial scale process for the preparation of l-cyclopropyl-2-(2- fluorophenyl)-ethanone of the Formula (1) and the use of this compound for the preparation of prasugrel.
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- PROCESS FOR PREPARING PRASUGREL
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The present invention is directed to an improved process for preparing, prasugrel and maleate salt of Prasugrel and, optionally other pharmaceutically acceptable salts from, prasugrel and said maleate salt, in high yields and purity, which can be used at industrial scale. The process of the present invention comprises the steps of bromination, condensation, acetylating and optionally converting into maleate salt and, if desired, conversion into another pharmaceutically acceptable salt from it. The present process is advantageous in terms of productivity, efficacy, purity and also prevents the use of toxic substances.
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Page/Page column 19-20
(2013/03/26)
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- Processes For Preparing Prasugrel And Pharmaceutically Acceptable Salts Thereof
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Disclosed are improved processes for preparing prasugrel compound of formula-(1), its intermediates and pharmaceutically acceptable salts.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF PRASUGREL HYDROCHLORIDE AND ITS INTERMEDIATES
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The present invention provides an improved process for the preparation of prasugrel and its pharmaceutical acceptable salt. Prasugrel chemically known as 2-acetoxy-5-(a- cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]-pyridine or 5-[2- cyclopropyl-l-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2,-c]pyridine- 2yl acetate and having the structural formula (I) and its pharmaceutically acceptable salts. The present invention also provides an improved process for the preparation of cyclopropyl 2-fluorobenzyl ketone, 2-Fluoro-a-cyclopropyl carbonylbenzyl bromide, 5,6,7,7a Tetrahydro-4H- theino-[3,2-c]- pyridone-2 p-toluenesulfonate and its hydrochloride salt.
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- PREPARATION OF PRASUGREL HYDROCHLORIDE
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The present application relates to process for the preparation of prasugrel, its pharmaceutically acceptable salts, and its intermediates.
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Page/Page column 27-28
(2012/02/15)
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- METHOD FOR PREPARING PHARMACEUTICALLY ACTIVE INGREDIENT AND INTERMEDIATES THEREOF
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The present invention is related to a safe and industrially applicable method for the preparation of 2-acetoxy-5-(2-fluoro-α-cyclopropyl- carbonyl-benzyl)-4,5,6,7-tetrahydro-4H-thieno[3,2-c]pyridine in a quality suitable for use as pharmaceutically active ingredient wherein the concentration of the impurities of the Formula.(XXIV) or (XXIVa) is reduced.
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Page/Page column 32
(2012/05/05)
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- PRASUGREL HYDROCHLORIDE CRYSTALLINE PARTICLES
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The present invention relates to prasugrel hydrochloride crystalline particles having mean particle size of more than about 10 μm, to the methods for the manufacture of said crystalline particles, and to pharmaceutical compositions comprising said crystalline particles.
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Page/Page column 7
(2012/03/11)
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- METHOD FOR PREPARING PRASUGREL
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The present invention relates to a method for synthesizing prasugrel, comprising the following steps: converting o-fluorobenzyl cyclopropyl ketone into α-cyclopropylcarbonyl-2-fluorobenzyl halide (compound 2) using dibromohydantoinhydantoin as halogenation reagent and acetic acid as solvent, then 2-oxo-4,5,6,7-tetrahydrothieno[3,2-c]pyridine p-toluenesulfonate (compound 4) is obtained with high yield by a concerted catalysis using a phase transfer catalyst and an inorganic salt, then is condensed and acylated to obtain prasugrel as a gum. The present invention also provides a method for purifying prasugrel comprising crystallizing using alcohols as a crystallization solvent to obtain prasugrel crystals with a high purity.
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Page/Page column 4
(2012/07/14)
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- METHOD FOR PREPARING PRASUGREL
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The present invention relates to a method for synthesizing prasugrel, comprising, the following steps: converting o-fluorobenzyl cyclopropyl ketone into α-cyclopropylcarbonyl-2-fluorobenzyl halide (compound 2) using dibromohydantoinhydantoin as halogenation reagent and acetic acid as solvent, then 2-oxo-4,5,6,7-tetrahydrothieno[3,2-c]pyridine p-toluenesulfonate (compound 4) is obtained with high yield by a concerted catalysis using a phase transfer catalyst and an inorganic salt, then is condensed and acylated to obtain prasugrel as a gum. The present invention also provides a method for purifying prasugrel comprising crystallizing using alcohols as a crystallization solvent to obtain prasugrel crystals with a high purity.
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Page/Page column 2
(2012/06/16)
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- NOVEL AND IMPROVED PROCESSES FOR THE PREPARATION OF PRASUGREL, ITS INTERMEDIATES AND PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to novel and improved processes for the preparation of prasugrel compound of formula-(1), its intermediates and pharmaceutically acceptable salts.
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- PHARMACEUTICAL COMPOSITION OF PRASUGREL AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to a pharmaceutical composition of prasugrel or its pharmaceutically acceptable salts thereof as well as process for its preparation. Formula (I).
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- PROCESS FOR THE PREPARATION OF 2-ACETOXY-5-(α -CYCLOPRPYLCARBONYL -2-FLUOROBENZYL)-4,5,6,7-TETRAHYDROTHIENO[3,2-C]PYRIDINE
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The present invention relates to a process for the preparation of 2-Acetoxy-5-(α-cycloprpylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine and pharmaceutically acceptable salt thereof using a 2-acetoxy-tetrahydrothienopyridine derivatives i.e. compound of formula (VI) and (VIII) or salt thereof or acid addition salt of 5-(α-cycloprpylcarbonyl-2-fluorobenzyl)-2-oxo-4,5,6,7-tetrahydrothieno[3,2-c]pyridine of formula (II). The present invention also relates to the process for the preparation of 2-acetoxy-tetrahydrothienopyridine derivatives i.e. compound of formula (VI) and (VIII) or salt thereof and acid addition salt of compound of formula (II).
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- PROCESS FOR THE PREPARATION OF PHARMACEUTICAL I NTERM EDIATES
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The invention relates to a process for the preparation of compounds of general formula (III), wherein R represents fluorine or chlorine atom and X represents chlorine or bromine atom, by halogenation of cyclopropyl benzyl ketone of general formula (II), wherein R represents fluorine or chlorine atom and the halogenation is carried out in the mixture of aqueous hydrogen halide and aqueous hydrogen peroxide in the presence of a water miscible solvent or in the presence of a phase transfer catalyst; or the halogenation is carried out in the mixture of sulfuric acid and an alkali metal salt of aqueous hydrogen halide. The process can be applied preferably on industrial scale.
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Page/Page column 11; 15-16
(2009/07/03)
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- IMPROVED PROCESS FOR THE PREPARATION OF PRASUGREL AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to an improved process for the preparation of prasugrel compound of formula- 1 and its pharmaceutically acceptable salts thereof.
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Page/Page column 22
(2009/06/27)
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- PROCESSES FOR THE PREPARATION OF PRASUGREL, AND ITS SALTS AND POLYMORPHS
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Processes for the preparation of prasugrel and its pharmaceutically acceptable salts thereof. Also disclosed are polymorphic forms of prasugrel hydrochloride and processes for their preparation.
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Page/Page column 41
(2009/06/27)
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- Oral dosage forms including an antiplatelet agent and an acid inhibitor
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The present disclosure provides oral dosage forms comprising an antiplatelet agent and an acid inhibitor, as well as methods of treating subjects with an antiplatelet agent and an acid inhibitor.
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Page/Page column 20-21
(2008/06/13)
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- Acid addition salts of hydropyridine derivatives
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Acid addition salts of 2-acetoxy-5-(α-cyclopropyl-carbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]-pyridine. The acid addition salts of tetrahydrothienopyridine derivatives of the present invention exhibit excellent oral absorption, metabolization into the active compound, and platelet aggregation-inhibiting effects, low toxicity, and excellent storage and handling stabilities, and are useful as medicaments, preferably preventive or therapeutic agents (particularly therapeutic agents) for diseases caused by a thrombus or an embolus, still more preferably preventive or therapeutic agents (particularly therapeutic agents) for thrombosis or embolism.
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