120202-71-3

Usage

Uses

Used in Pharmaceutical Industry:
CLOPIDOGREL RELATED COMPOUND C (20 MG) (METHYL (-)-(R)-(O-CHLOROPHENYL)-6,7-DIHYDROTHIE-NO[3,2-C]PYRIDINE-5(4H)-ACETATE, HYDROGEN SULFATE) is used as an antithrombotic agent for preventing blood clot formation and reducing the risk of heart attack, stroke, and other thrombotic events in patients with certain medical conditions.

InChI:InChI=1/C16H16ClNO2S.H2O4S/c1-20-16(19)15(12-4-2-3-5-13(12)17)18-8-6-14-11(10-18)7-9-21-14;1-5(2,3)4/h2-5,7,9,15H,6,8,10H2,1H3;(H2,1,2,3,4)/t15-;/m1./s1

Upstream product

• 113665-84-2 (S)-(+)-clopidogrel 
• 120202-69-9 methyl (R)-2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)acetate 
• 1233025-55-2 (S)-clopidogrel hydrogen sulfate 
• 141109-18-4 (S)-(+)-α-(2-thienylethylamino)-α-(2-chlorophenyl)acetic acid methyl ester hydrochloride 
• 50-00-0 formaldehyd 
• 7664-93-9 sulfuric acid 
• 909279-85-2 clopidogrel camphorsulfonate 
• 90055-68-8 (+/-)-methyl-(2-chlorophenyl)-(4,5,6,7-4H-thieno[3,2,-c]pyrid-5-yl) acetamide 
• 444891-19-4 2-bromo-2-(2-chlorophenyl)acetonitrile 
• 444728-11-4 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridine-5(4H)-yl)acetonitrile 
• 2856-63-5 2-Chlorophenylacetonitrile 
• 90055-55-3 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridine-5(4H)-yl)acetic acid 
• 30433-91-1 [2-(2-thyenyl)ethyl]amine 
• 28783-41-7 6,7-dihydro-4H-thieno[3,2-c]pyridine hydrochloride 

Downstream Products

• 1326217-43-9 (S)-methyl 2-(2-bromo-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate 
• 90055-48-4 clopidogrel 
• 1373492-22-8 5-(2-chloro-1-(2-chlorophenyl)ethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 1373492-23-9 2-((2-chlorophenyl)-2-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)ethyl)malonic acid diethyl ester 
• 1373491-72-5 4-(2-chlorophenyl)-4-(6,7-dihydro-4H-thieno[3,2-c]pyridine-5-yl)butyric acid ethyl ester 
• 1373491-51-0 4-(2-chlorophenyl)-4-(6,7-dihydro-4H-thieno[3,2-c]pyridine-5-yl)butan-1-ol 

Relevant academic research and scientific papers

Similarity of solid state structures of R- and S-isomers of clopidogrel hydrogensulphate salt

The present study showed, that the crystal structures of R-isomer and the polymorphic form 1 of clopidrogrel hydrogensulphate S-isomer are very similar.

Copper (II) bromide catalysed one pot bromination and amination for the green, cost-effective synthesis of clopidogrel

Copper (II) bromide catalyzed one pot α-bromination and followed by amination of a benzylic ester is reported. The α-bromination of ester by copper (II) bromide generates copper (I) bromide and HBr. The copper (I) bromide is oxidized to copper (II) bromide by N-Methylmorpholine-N-Oxide (NMO) in presence of HBr. The amines undergo nucleophilic substitution reaction with α-brominated ester compound. This methodology was applied for the synthesis of the familiar antiplatelet drug clopidogrel. This green process is an alternate to classical methods for the synthesis of clopidogrel, which requires, generates stochiometric amount of brominating agents and HBr, respectively.

Preparation method of clopidogrel hydrogen sulfate

The invention relates to a preparation method of clopidogrel hydrogen sulfate. The preparation method comprises the following steps: reacting (S)-o-chlorophenylglycine methyl ester with 1, 1, 1, 3, 3,3-hexamethyldisilazane to obtain trimethylsilyl protected (S)-o-chlorophenylglycine methyl ester; in the presence of acetonitrile, superfine powder potassium carbonate and the trimethylsilyl protected (S)-o-chlorophenylglycine methyl ester, adding 2- (2-bromoethyl) thiophene, evaporating acetonitrile in batches, adding water and methyl acetate, extracting to obtain a methyl acetate solution of (S)-2-thiophene ethylamino-2-chlorophenylmethyl acetate, dropwise adding concentrated hydrochloric acid, carrying out pulping and cooling to obtain (S)-2-thiophene ethylamino methyl-2-chlorophenyl acetate hydrochloride, mixing the (S)-2-thiophene ethylamino methyl-2-chlorophenyl acetate hydrochloride with a formaldehyde aqueous solution for reaction, and carrying out reaction with concentrated sulfuric acid to obtain the clopidogrel hydrogen sulfate. According to the method, the high-purity (S)- 2-thiophene ethylamino-2-chlorophenyl methyl acetate hydrochloride and clopidogrel hydrogen sulfate can be obtained with high efficiency and high yield, and the method is suitable for industrial production.

Preparation method of clopidogrel hydrogen sulfate and intermediate N-(2-thiopheneethyl) methyleneimine of clopidogrel hydrogen sulfate

The invention discloses a preparation method of clopidogrel hydrogen sulfate and an intermediate N-(2-thiophene ethyl) methyleneamine of the clopidogrel hydrogen sulfate. The synthesis method of the intermediate comprises the step of carrying out an Eschweiler-Clarke methylation reaction by taking 2-thiophene ethylamine and paraformaldehyde as raw materials to obtain the N-(2-thiophene ethyl) methyleneamine. The invention also provides a method for preparing clopidogrel hydrogen sulfate. According to the synthesis method provided by the invention, the required solid product (N-(2-thiopheneethyl) methyleneimine) is synthesized in one step, the synthesis method is simple, the qualified solid compound is directly obtained, the time and the raw material cost are saved, the storage and the transportation are convenient, the purity is good, the yield is high, and the synthesis method is suitable for industrial production.

Preparation method of clopidogrel hydrogen sulfate intermediate

The present invention relates to a preparation method of a clopidogrel hydrogen sulfate intermediate. (+)-2-chlorophenylglycine methyl ester and alpha-thiopheneethanol p-toluenesulfonate are adopted as raw materials, a reaction solvent and an acid-binding agent are added for a condensation reaction, the condensation reaction process is divided into a first stage and a second stage, and when 60-95% of the condensation reaction is completed, first-stage reaction is completed; after the first-stage reaction is completed, firstly part of the reaction solvent is removed, and then second-stage reaction is carried out; and after the second-stage reaction is completed, a target product is obtained, namely the clopidogrel hydrogen sulfate intermediate. After the first-stage reaction is completed, part of the reaction solvent is removed firstly, and then the second-stage reaction is continued, so that the concentration of the reaction material can be increased in the later stage of the condensation reaction, the use amount of the reaction solvent is reduced, and racemization and side reaction in the reaction process are effectively inhibited, thereby improving the chiral purity of the product, increasing the yield, reducing the use of auxiliary materials greatly, and reducing the production cost.

Method for preparing high-purity type-II crystal form hydrogen sulfate clopidogrel

The invention discloses a method for preparing high-purity type-II crystal form hydrogen sulfate clopidogrel. The method comprises the following steps: dissolving a first clopidogrel free alkali crudeproduct into dichloromethane, performing decontamination by using a 4wt% sodium hydroxide solution, performing alkali wash on an organic phase, and performing drying, suction filtration and concentration so as to obtain a seconda clopidogrel free alkali crude product; and adding ethyl acetate or a mixed liquid of ethyl acetate and acetonitrile, increasing the temperature to 37-39 DEG C, adding dropwise concentrated sulfuric acid to be subjected to crystallization, performing room-temperature crystallization, performing filtering, and drying filter cakes so as to obtain a final product, namelytype-II crystal form hydrogen sulfate clopidogrel. The method is mild in reaction condition and free of toxic or harmful substance, in addition, the amount of a precursor solvent is reduced, the reaction time is shortened to 4-6 hours from 14-16 hours, the energy consumption is reduced, related substances of the type-II crystal form hydrogen sulfate clopidogrel are ensured to meet various domestic and abroad standards, and generation of impurities is avoided when strong acids are added dropwise; and the obtained type-II crystal form hydrogen sulfate clopidogrel is high in purity and high in yield.

A preparation method of clopidogrel hydrogen sulfate type II

The invention discloses a preparation method of clopidogrel hydrogen sulfate type II. The method comprises the following steps: (4) taking clopidogrel free alkali as a raw material, and reacting the clopidogrel free alkali with (1R)-(-)-10-camphorsulfonic acid in a reaction solvent to obtain clopidogrel camphorsulfonate, and hydrolyzing under an alkaline condition to obtain clopidogrel free alkali; and then preparing the clopidogrel hydrogen sulfate type II by taking the clopidogrel free alkali obtained in the step (4) as a raw material. The synthetic route is simple, the used solvent is cheap, the cost is saved, the generation of waste liquid is reduced, the recycling of the solvent is improved, and the prepared clopidogrel hydrogen sulfate type II has the characteristics of high purity,good quality, high yield, good stability, suitability for industrial mass production and the like.

A preparation method of clopidogrel hydrogen sulfate type II

The invention discloses a preparation method of clopidogrel hydrogen sulfate type II. According to the method, clopidogrel hydrogen sulfate type II is prepared by taking clopidogrel free alkali as a raw material, and a preparation method of clopidogrel free alkali comprises the following steps: (1) preparing a reaction mixed solution of R-chloromandelic acid methyl ester by the reaction of R-chloromandelic acid and methanol in an organic solvent and in the presence of a catalyst; (2) mixing the reaction mixed solution of R-chloromandelic acid methyl ester with an organic base and a catalyst, reacting in the presence of benzenesulfonyl chloride to obtain a reaction mixed solution of methyl 2-benzenesulfonyl-2-chlorophenylacetate; (3) mixing the reaction mixed solution of methyl 2-benzenesulfonyl-2-chlorophenylacetate obtained in the step (2) with 4,5,6,7-Tetrahydrothieno[3,2,c] pyridine hydrochloride and potassium carbonate for reaction to obtain the clopidogrel free alkali. According to the method, the solvent does not need to be supplemented in the last two steps, the solvent is directly used, and the reaction liquid concentration time is saved.

Synthetic hydrosulfuric acid clopidogrel and intermediate of the new method (by machine translation)

The invention relates to a synthesis of the clopidogrel hydrogen sulfate of the new method, through 2 - thiophene ethylamine and N - benzyl - 2 - (2 - chlorophenyl) - 2 - carbonyl acetamide generate condensation reaction, generating imine; imine asymmetric hydrogenation reaction is reduced to the corresponding secondary amine. Under acidic conditions, secondary amine with formaldehyde generating ring, get the clopidogrel free base, then acidified by sulfuric acid, to obtain the clopidogrel hydrogen sulfate. The present invention provides a synthetic route of the short, relates to the reaction are classical organic chemical reaction, mild reaction conditions, the operation is simple, with high enantio-selectivity, high yield, high turn over number of characteristics, the vast majority of the substrate in the thousandths of a dosage of the catalyst obtained in the circumstances of 99% or more of the conversion and 97% -99% ee value of, to achieve the highest transformed number 100000, has extremely high industrial application value. (by machine translation)

The clopidogrel hydrogen sulfate synthesis method (by machine translation)

The invention discloses a clopidogrel hydrogen sulfate synthesis method, comprises the following steps: S1, 2 - (2 - thiophene) ethanol tosylates synthetic, S2, (+) - O-chlorobenzene glycine methyl brown oil of synthetic, S3, (S)- 2 - (2 - thiophene ethylamine) (2 - chlorophenyl) acetic acid methyl ester hydrochloride of synthetic, S4, the finished synthetic; the invention with conventional clopidogrel hydrogen sulfate existing synthesis method, the processing operation is more convenient, after treatment is simple, and is suitable for commercial production; high yield, few by-products, impurity removal easier; simple and easy to obtain, the cost is cheap. (by machine translation)