cas 150322-43-3, Prasugrel | Articles data

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A "bunch" method for preparing method for prasugrel
The present invention relates to a method for preparing prasugrel through a one-pot-porridge method. According to the method, in the presence of an alkali, 5,6,7,7a-tetrahydrothieno[3,2-c]pyridine-2(4H)-one hydrochloride and cyclopropyl-2-bromo-2-(2-fluorophenyl)ethyl ketone react and then continuously react with acetic anhydride without an intermediate treatment, and finally the target compound prasugrel is collected from the reaction products. The technical scheme of the present invention has the following characteristics that: the hydroxyl protection is not required, the use of DMF, toluene and other strongly-toxic and high-boiling point solvents is avoided, the process is safe and easy to control, the steps are simplified, the post-treatment is simple, the purity and the yield of the product is maintained or improved, the cost is reduced, and the large-scale production is easily achieved.
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Paragraph 0032-0041

(2019/04/04)

A process for the preparation of the new process prasugrel hydrochloride
The invention discloses a novel synthesis process of prasugrel. The novel synthesis process comprises the steps: firstly, carrying out benzyl protection by taking 4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridine, benzaldehyde and sodium triacetoxyborohydride as starting raw materials to generate 5-benzyl-4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridine; then, brominating the 5-benzyl-4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridine by using hydrobromic acid to obtain 2-bromo-5-benzyl-4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridine; next, catalytically synthesizing 2-acetoxy-5-benzyl-4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridine by taking palladium acetate as a catalyst and XPhos as a ligand; and finally, carrying out hydrodebenzylation, and coupling the product with alpha-bromo-o-fluorobenzyl cyclopropyl ketone to obtain a target molecule 2-acetoxy-5-(alpha-cyclopropylcarbonyl-2-fluorobenzyl)-4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridine hydrochloride, i.e., the prasugrel hydrochloride. The process is simple, convenient and novel in route, easy to obtain raw materials, mild in condition, convenient to operate, high in total yield up to 80-90% and suitable for large-scale production.
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(2018/09/02)

Preparation method of Prasugrel intermediate and prasugrel crude product
The invention relates to a preparation method of a prasugrel intermediate and a prasugrel crude product. The prasugrel intermediate and the prasugrel crude product are finally prepared by preparing aprasugrel intermediate of level I and a prasugrel intermediate of level II. The preparation method adopts low-cost raw materials, so that the production cost is lowered, and the dependency of the rawmaterials is reduced; the method is mild in reaction conditions and high in yield; furthermore, as important intermediates, the prasugrel intermediate of level I and the prasugrel intermediate of level II are simple in preparation process, so that the control difficulty of workers is reduced, and the working efficiency is increased.
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(2018/09/08)

A high-purity prasugrel preparation method
A high-purity prasugrel preparation method, compared with the prior art, the invention adopts the new preparation process, by acylation and esterification, condensation, dehydrohalogenation, hydrolysis, cyclization and acetylation can be for preparing high-purity prasugrel, mild conditions, yield is higher; at the same time 1 - alkenyl - [six hydrogen pyrazoles - 1 - (α - cyclopropyl carbonyl - 2 - fluorobenzyl) - 2 - yl] - acetic acid R ester alkali is added to the catalyst so that the hydrolysis reaction can be carried through to the end, further improves the reaction yield, in addition to the 2 - acetoxy - 5 - (α - cyclopropyl carbonyl - 2 - fluorobenzyl) - 4, 5, 6, 7 - tetrahydro-thieno [3, 2 - c] pyridine has further purification, to obtain a high purity prasugrel, and the unexpected technical effects.
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(2018/07/30)

A Simple and Efficient Method for the Preparation of α-Halogenated Ketones Using Iron(III) Chloride and Iron(III) Bromide as Halogen Sources with Phenyliodonium Diacetate as Oxidant
α-Halogenated ketones are both unique structure moieties existing in biologically natural products and valuable synthetic intermediates for the preparation of functional molecules. An efficient and scalable method for the preparation of α-halogenated ketone using iron (III) chloride and iron (III) bromide as halogen sources with phenyliodonium diacetate as oxidant has been developed, featuring mild reaction conditions, environmentally friendly reagents, and wide substrate scope. Notably, the three-step synthesis of drug prasugrel was achieved using this developed method as a key step with 30% yield on gram-scale. Additionally, the reaction mechanism involving chloride cation was proposed based on some preliminary control experiments. (Figure presented.).
Tang, Shi-Zhong,Zhao, Wenshuang,Chen, Tao,Liu, Yang,Zhang, Xiao-Ming,Zhang, Fu-Min
p. 4177 - 4183
(2017/12/18)

PROCESS FOR THE PREPARATION OF HIGH-PURITY PRASUGREL
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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(2018/04/11)

Prasugrel synthetic method
The invention relates to a synthetic method of prasugrel. 2-bromo-1-cyclopropyl-2-(2-fluorophenyl) acetone and 4,5,6,7-tetrahydro thieno [3,2-C] pyridine hydrochloride are condensed under the action of alkali, so that an intermediate, namely 1-cyclopropyl-2-(6,7-dihydro thieno [3,2-C] pyridine-5(4H)-yl)-2-(2-fluorophenyl) acetone, is obtained, and then oxidation and acylation are carried out, so that prasugrel is obtained. The synthetic method of prasugrel has the advantages that a prasugrel intermediate is synthesized, condensation yield is high, operating steps are simple, protection and deprotection steps in the prior art are eliminated, and cost is greatly saved.
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Paragraph 0025-0026

(2017/08/23)

Intermediate for synthetizing prasugrel, preparation method of intermediate, and method for synthetizing prasugrel
The present invention discloses an intermediate for synthetizing prasugrel, a preparation method of the intermediate, and a method for synthetizing prasugrel by using the intermediate. In the invention, cyclopropyl-2-fluorobenzyl ketone reacts with different chlorine source compounds under the action of an oxidizing agent to obtain the intermediate, and the intermediate is subjected to condensation with 2-Oxo-2,4, 5,6,7,7a-Tetrahydrothieno[3,2-c]pyridine-2(4H)-one hydrochloride and then is subjected to acetylation to obtain prasugrel; and the synthetizing route is simple, the cost is low, and operation is convenient.
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(2017/09/02)

AN IMPROVED PROCESS FOR THE PREPARATION OF PRASUGREL INTERMEDIATES
The present invention relates to an improved method for preparing 2-oxo prasugrel, 5-(andalpha;-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2,-c]pyridine (chemical formula 1), which is a major intermediate of prasugrel. More specifically, the present invention provides an improved method which is characterized by adding water as a catalyst and dividedly feeding an inorganic basic composition when 2-oxo prasugrel is synthesized through a condensation reaction between andalpha;-cyclopropylcarbonyl-2-fluorobenzylbromide represented by chemical formula 2 and 2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2,-c]pyridine hydrochloride represented by chemical formula 3.COPYRIGHT KIPO 2017
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Paragraph 0073; 0074

(2017/12/01)

Method for preparing prasugrel intermediate
The invention discloses a method for preparing a prasugrel intermediate 5-(alpha-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-1,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine. The method comprises a following reaction route. As a result of experiments, the method provided by the invention has the advantages of simple operation, mild reaction conditions, low requirement on equipment, inexpensive and easy-to-obtain raw materials, high yield, and low production cost. An adopted solvent can synchronously recovered. The method can be easily applied in large-scale productions. The method meets the requirements of prasugrel industrialized production, and has industrial application value.
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(2016/10/10)

Method for preparing prasugrel
The invention provides a compound represented by a general formula II. In the general formula II, R1, R2 and R3 can be identical or different and respectively represent one of the following atoms or groups: a hydrogen atom, a substituted or unsubstituted alkyl group and a substituted or unsubstituted aryl group. According to the invention, an intermediate is utilized to prepare prasugrel, thus operation is simplified, reaction condition is mild, reaction is stable and yield is high; and particularly, in the process of preparing prasugrel utilizing the intermediate, a 'one-pot porridge' operation process is adopted, so as to greatly simplify the reaction operation.
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Paragraph 0086-0087

(2016/12/07)

A low-cost method for preparing environmental protection of prasugrel
The invention relates to a low-cost environment-friendly preparation method of prasugrel. The method comprises the following steps: carrying out N,N-disubstitution reaction on the initial raw material 2-o-fluorophenylaminoacetonitrile and tert-butyl acrylate, carrying out Grignard reaction to obtain 1-cyclopropyl-2-o-fluorophenyl-N,N-2-(di-tert-butoxycarbonyl)ethylaminoethyl ketone (III), carrying out intramolecular condensation to obtain N-alpha-cyclopropylcarbonyl-1-o-fluorobenzyl-3-tert-butoxycarbonylpiperidyl-4-one (IV), carrying out SN2 substitution to obtain N-alpha-cyclopropylcarbonyl-1-o-fluorobenzyl-3-(2-alkoxycarbonyl)ethylpiperidyl-4-one (V), reacting with zinc sulfide-acetic acid and acetic anhydride-triethylamine to obtain 2-acetoxy-5-(alpha-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-thiophano[3,2-c]pyridine (VI), and salifying (VI) to obtain the prasugrel. The method has the advantages of cheap and accessible raw materials, safe technique and environmental protection, and is simple to operate.
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(2016/10/09)

Method for preparing thrombosis-resisting medicine namely prasugrel
The invention discloses a method for preparing a thrombosis-resisting medicine namely prasugrel. The method comprises the following steps of (1) performing nitrogen protection, in the presence of copper iodide, XPhos and alkali, enabling 1-cyclopropyl-2-bromine-2-(2-fluorophenyl)-2-ethanone and 2-oxo-2, 4, 5, 6, 7-7a-tetrahydro thieno [3,2-c] pyridine hydrochloride to be subjected to a reaction so as to obtain 5-(alpha-cyclopropane carbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-thieno [3,2-c] pyridine; and (2) mixing the 5-(alpha-cyclopropane carbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-thieno [3,2-c] pyridine obtained in the step (1) with anion exchange resin, then adding acetyl chloride, and performing a stirring reaction so as to obtain the prasugrel. The method for preparing the prasugrel disclosed by the invention is high in yield, easy to treat and suitable for industrialized production.
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Paragraph 0048-0062; 0069; 0070

(2017/05/23)

An anti-platelet drug prasugrel method for the preparation of (by machine translation)
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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(2016/12/16)

PROCESS FOR THE PREPARATION OF PRASUGREL AND SEVERAL NOVEL CRYSTALLINE FORMS OF PRASUGREL HYDROCHLORIDE
Disclosed herein are a process or method for the preparation of prasugrel and several novel crystalline forms of prasugrel hydrochloride. The process comprises preparation of prasugrel by acetylation in solvents which have low boiling point and/or low toxicity, and the process not only avoids using solvents which have high boiling point and/or high toxicity such as toluene, acetonitrile and so on, but also resolves the problem about thermal instability of prasugrel, and the loss of prasugrel is reduced, as well as the yield is raised. The yield of prasugrel is higher than 85% and the purity is higher than 99.5%. The process can prepare prasugrel and its pharmaceutically acceptable salts. The novel crystalline forms of prasugrel hydrochloride are crystalline form H1, H2 and H3, and their performance in oral absorbability, activating metabolism and inhibiting platelet aggregation is excellent. They have a low toxicity and good thermal stability, and are applicable to the preparation of a drug for preventing or treating diseases caused by thrombosis or embolism.
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Paragraph 0085

(2014/06/23)

IMPROVED PROCESS FOR THE PREPARATION OF PRASUGREL AND INTERMEDIATE THEREOF
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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Page/Page column 17

(2014/08/07)

PROCESS FOR PREPARING PRASUGREL
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 25

(2013/03/26)

Identification and synthesis of impurities formed during prasugrel hydrochloride preparation
Prasugrel hydrochloride (1), an important platelet inhibitor is used for the reduction of thrombotic cardiovascular events. During laboratory I optimization and later its bulk synthesis the formation of various impurities was observed. The impurities formed were monitored and their structures were tentatively assigned on the basis of their fragmentation patterns in LC-MS. Most of the impurities were synthesized and their assigned constitutions confirmed by co-injection in HPLC. We describe herein the formation, synthesis and characterization of these impurities. Present study will be of immense help to others to obtain chemically pure prasugrel hydrochloride.
Umasankara Sastry,Nageswrara Rao,Appi Reddy,Gandhi
p. 7783 - 7789
(2013/09/23)

PROCESS FOR PREPARING A PHARMACEUTICAL COMPOUND
The object of the present invention is a one-pot process for preparing the 2-acetoxy-5-(2-fluoro-α-cyclopropyl-carbonyl-benzyl)-4,5,6,7-tetrahydro-4H-tieno[3,2-c]-pyridine (prasugrel) of the formula (I) by reacting the 5,6,7,7a-tetrahydro-4H-tieno[3,2-c]-pyridine-2-on of the formula (II) with 2-bromo-1-cyclopropyl-2-(2-fluorophenyl)-etanone of the formula (III) or with 2-chloro-1-cyclopropyl-2-(2-fluorphenyl)-etanone of the formula (IIIa) and acetylating of the formed compound of the formula (IV), wherein the reaction is carried out in the presence of an organic base with an acetylation agent without isolating the compound of the formula (IV). The coupling and acetylation are carried out in the presence of the same organic base such as triethylamine, N,N-diisopropyl-ethylamine or pyridine. At the end of the process the prasugrel of the formula (I) is purified by recrystallization from an organic solvent or a mixture of solvents.
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(2013/03/26)

An improvement to the preparation of prasugrel hydrochloride
An efficient synthesis of prasugrel, a thienopyridine ADP-receptor antagonists, is described. A thienopyridine intermediate was prepared by N-protection, boric acid substitution and N-substitution. After acid hydrolysis of the methyl ether and subsequent acetylation, prasugrel was obtained with a total yield of 50% after seven linear steps from 4,5,6,7-tetrahydrothieno [3,2-c]pyridine and 2-bromo-1-cyclopropyl-2-(2- fluorophenyl)ethan-1-one as raw materials.
Ou, Wenhua,Yi, Weiyin,Liu, Feng,Pan, Xianhua,Peng, Xijiang
p. 369 - 371
(2013/07/26)

Efficient synthesis of prasugrel, a novel P2Y12 receptor inhibitor
An efficient synthesis of prasugrel, a novel P2Y12 receptor inhibitor, is described. The cyclopropyl-phenylethanone intermediate was prepared by cyanide substitution, bromination, N-substitution, and the Grignard reaction. After acid hydrolyzation of the methyl ether and subsequent acetylation, the title product was obtained with a total yield of 21% after 10 linear steps from simple and commercially available raw materials.
Pan, Xianhua,Huang, Rui,Zhang, Jianshui,Ding, Liping,Li, Weijin,Zhang, Qunhui,Liu, Feng
p. 5364 - 5366
(2012/10/29)

AN IMPROVED PROCESS FOR THE PREPARATION OF PRASUGREL HYDROCHLORIDE AND ITS INTERMEDIATES
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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(2012/01/14)

Process improvements of prasugrel hydrochloride: An adenosine diphosphate receptor antagonist
An improved process for the synthesis of prasugrel hydrochloride with an overall yield of 58%, 99.9% purity, and meeting all other quality requirements is described.
Aalla, Sampath,Gilla, Goverdhan,Metil, Dattatray Shamrao,Anumula, Raghupathi Reddy,Vummenthala, Prabhaker Reddy,Padi, Pratap Reddy
p. 240 - 243
(2012/06/04)

Processes For Preparing Prasugrel And Pharmaceutically Acceptable Salts Thereof
Disclosed are improved processes for preparing prasugrel compound of formula-(1), its intermediates and pharmaceutically acceptable salts.
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(2012/08/27)

METHOD FOR PREPARING PHARMACEUTICALLY ACTIVE INGREDIENT AND INTERMEDIATES THEREOF
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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(2012/05/05)

PREPARATION OF PRASUGREL HYDROCHLORIDE
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 31

(2012/02/15)

PRASUGREL HYDROCHLORIDE CRYSTALLINE PARTICLES
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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(2012/03/11)

METHOD FOR PREPARING PRASUGREL
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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(2012/07/14)

METHOD FOR PREPARING PRASUGREL
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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(2012/06/16)

METHOD OF PRODUCING HIGHLY PURE PRASUGREL AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
A method for the production of 5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]- 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate of formula (I) or its salts, characterized in that the compound of formula (III) in the form of a salt with an arene sulfonic acid is reacted with the compound of formula (XV), wherein Y means: chlorine, bromine, or an OR4 group, wherein R4 means an alkane sulfonic group or arene sulfonic group, in an organic solvent in the presence of an inorganic base or organic base, to give, after addition of an acetylating reagent and organic base to the reaction mixture, the compound of formula (I), which, after addition of a co-solvent, is crystallized from the reaction mixture, and the compound of formula (I) is optionally purified by crystallization and optionally converted to a salt by reaction with an organic or inorganic acid in a suitable solvent. (Formulae (I), (III), (XV)
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Page/Page column 12; 13

(2011/06/16)

NOVEL AND IMPROVED PROCESSES FOR THE PREPARATION OF PRASUGREL, ITS INTERMEDIATES AND PHARMACEUTICALLY ACCEPTABLE SALTS
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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(2011/04/26)

PHARMACEUTICAL COMPOSITION OF PRASUGREL AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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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(2011/08/21)

A PROCESS FOR MAKING PRASUGREL AND ITS INTERMEDIATES
The present invention relates to 5-R-2-acetoxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine compound of the general formula (A) and/or acid addition salts thereof, to processes for their preparation and their use as an intermediate in making prasugrel.
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(2011/04/18)

IMPROVED PROCESS FOR PREPARING A PHARMACEUTICAL COMPOUND
The object of the present invention is a one-pot process for preparing the 2-acetoxy-5-(2-fluoro-α-cyclopropyl-carbonyl-benzyl)-4,5,6,7-tetrahydro-4H-tieno[3,2-c]-pyridine (prasugrel) of the formula (I) by reacting the 5,6,7,7a-tetrahydro-4H-tieno[3,2-c]-pyridine-2-on of the formula (II) with 2-bromo-1-cyclopropyl-2-(2-fluorophenyl)-etanone of the formula (III) or with 2-chloro-l-cyclopropyl-2-(2-fluorphenyl)-etanone of the formula (IIIa) and acetylating of the formed compound of the formula (IV), wherein the reaction is carried out in the presence of an organic base with an acetylation agent without isolating the compound of the formula (IV). The coupling and acetylation are carried out in the presence of the same organic base such as triethylamine, N,N-diisopropyl-ethylamine or pyridine. At the end of the process the prasugrel of the formula (I) is purified by recrystallization from an organic solvent or a mixture of solvents.
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(2011/07/09)

PROCESS FOR PREPARING PHARMACEUTICAL COMPOUNDS AND INTERMEDIATE COMPOUNDS
The object of the present invention is a process for preparing the 2-acetoxy-5-(2-fluor-α- cyclopropyl-carbonyl-benzyl)-4,5,6,7-tetrahydro-4H-tieno[3,2-c]pyridine (prasugrel) of the formula (I). The process starts form crystalline 5-trityl-4,5,6,7-tetrahydro-tieno[3,2- c]pyridine of the formula (VI). Further objects of the present invention are two novel crystalline forms of 5-trityl-4,5,6,7- tetrahydro-tieno[3,2-c]pyridine of the formula (VI) and the use thereof for preparing the compound of the formula (V) and process preparing thereof.
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(2011/07/09)

A PROCESS FOR THE PREPARATION OF PRASUGREL HCL SALT
The present invention relates to process for the preparation of Prasugrel HCl having formula (I).
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(2011/10/13)

A PROCESS FOR MAKING PRASUGREL
The present invention relates to A compound of general Formula (A), and/or acid addition salts thereof, wherein R is a hydrogen atom or a nitrogen-protecting group or an alpha- cyclopropylcarbonyl-2-fluorobenzyl group and R1,R2 is independently a C1-C10 alkyl group, optionally having one or more carbons substituted by a hydroxy group, or R1,R2 together with the bridging nitrogen may form a ring comprising from 3 to 10 carbon atoms, optionally also comprising another nitrogen, oxygen or sulfur atom in the ring and/or a nitrogen-, oxygen-, or sulfur-comprising substituent on the ring, to a process of making and use in making prasugrel.
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(2011/10/05)

A METHOD FOR THE MANUFACTURE OF HIGHLY PURE PRASUGREL
The invention deals with preparation of the substance prasugrel, using 3- cyclopropyl-1 -(2-fluorophenyl)-3-oxopropyl methanesulfonate for alkylation of 2-oxo- thienotetrahydropyridine, which may be in the form of a salt, e.g. with hydrochloric acid or p-toluenesulfonic acid. The resulting compound of formula II is acylated, preferably with acetanhydride, preferably directly in the reaction mixture without isolation, and the produced prasugrel of formula I can then be crystallized directly from the reaction mixture.
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Page/Page column 8-9

(2010/06/17)

METHOD OF MANUFACTURING 5-[2-CYCLOPROPYL-1-(2-FLUOROPHENYL)-2-OXOETHYL]-4,5,6,7-TETRAHYDROTHIENO[3,2-C]PYRIDIN-2-YL ACETATE (PRASUGREL)
A method of manufacturing 5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate, known under the INN name prasugrel of formula (I), in which the substance of formula (VI) is reacted with a cyclopropyl magnesium halide to produce the substance of formula (V), which reacted with methanesulfonyl chloride to give the methanesulfonate of formula (IV), which is further reacted with the compound of formula (III) to be converted the substance of formula (II) and the latter is converted to the substance of formula (I) with an acetylation agent.
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Page/Page column 6

(2010/09/17)

PROCESS FOR THE PREPARATION OF 2-ACETOXY-5-(α -CYCLOPRPYLCARBONYL -2-FLUOROBENZYL)-4,5,6,7-TETRAHYDROTHIENO[3,2-C]PYRIDINE
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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(2009/10/30)

PRASUGREL SALTS WITH IMPROVED PROPERTIES
Acid addition salts of 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine with sulfuric acid or sulfonic acids, pharmaceutical compositions comprising the same and processes for the production thereof. The acid addition salts have a low toxicity.
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Page/Page column 15-16

(2009/10/09)

PROCESS FOR PRODUCTION OF PRASUGREL HYDROCHLORIDE HAVING HIGH PURITY
An object of the present invention is to provide prasugrel hydrochloride with a reduced content of CATP, and the like. In the formulae, R represents a protecting group for a hydroxyl group. A method for producing prasugrel hydrochloride represented by the above formula is provided, characterized by comprising, in step (i), controlling, at low values, the temperature during the addition, optionally dropwise, of a chlorinating agent and the reaction temperature after the addition, optionally dropwise, of the chlorinating agent.
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Page/Page column 12

(2009/12/07)

IMPROVED PROCESS FOR THE PREPARATION OF PRASUGREL AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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 22-23

(2009/06/27)

PROCESSES FOR THE PREPARATION OF PRASUGREL, AND ITS SALTS AND POLYMORPHS
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 43-44

(2009/06/27)

PROCESS FOR PRODUCING HIGH-PURITY PRASUGREL AND ACID ADDITION SALT THEREOF
The present invention is directed to providing prasugrel hydrochloride or the like with a reduced content of OXTP. A method for producing prasugrel hydrochloride with a reduced content of OXTP, comprising dissolving free prasugrel containing OXTP in an inert solvent and adding hydrochloric acid optionally dropwise to the solution for reaction is also provided.
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Page/Page column 10

(2009/01/24)

Oral dosage forms including an antiplatelet agent and an acid inhibitor
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 21

(2008/06/13)

MEDICINAL COMPOSITION
A pharmaceutical composition containing a drug (A), a waxy substance (B), and synthetic aluminum silicate and/or hydrous silicon dioxide (C). The invention provides a granular pharmaceutical composition suitable for providing a pharmaceutical characterized in that adhesion of granules thereof onto a granulation apparatus during granulation is minimized and caking of the granules is suppressed.
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(2008/06/13)

Acid addition salts of hydropyridine derivatives
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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(2008/06/13)

MEDICINAL COMPOSITIONS
The present invention relates to a granular pharmaceutical composition comprising a drug having a disagreeable taste, a wax and a sugar alcohol; a method for preparing the same; and a pharmaceutical product for oral administration, comprising the granular composition. The product excellently masks a disagreeable taste possessed by a drug and provides good sensation upon oral administration, and therefore is easily ingested by even the elderly, children, and patients suffering dysphagia. Moreover, the product is suitable for administration using tube.
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(2008/06/13)

2-silyloxy-tetrahydrothienopyridine, salt thereof and process for preparing the same
A 2-silyloxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine represented by the formula (I): STR1 wherein R 1, R 2 and R 3 each independently represent an alkyl group having 1 to 10 carbon atoms or an aryl group,and a salt thereof and a process for preparing the same, and a 5-alkyl-2-silyloxy-4,5,6,7-tetrahydrothieno[3,2-c]-pyridine represented by the formula (IV): STR2 wherein R 1, R 2 and R 3 represent the same meanings as described above; R 4 represents a hydrogen atom, an alkoxycarbonyl group having 2 to 10 carbon atoms, an acyl group having 2 to 10 carbon atoms or a cyclo-alkylcarbonyl group having 4 to 10 carbon atoms; andR 5 represents a halogen atom, an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms,which is useful as a synthetic intermediate of an antiplatelet medicine and an elastase inhibitor, etc., and a process for preparing the same.
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(2008/06/13)