- Preparation method of clopidogrel hydrogen sulfate
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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.
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Paragraph 0075; 0078-0079; 0082; 0085-0086; 0089; 0092-0093
(2021/02/10)
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- Iridium and bis(4-nitrophenyl)phosphoric acid catalysed amination of diol by hydrogen-borrowing methodology for the synthesis of cyclic amine: Synthesis of clopidogrel
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The borrowing hydrogen method is an environmentally benign process for the synthesis of amines, as H2O is the side product. A new green process for the amination of diol by [Ir] catalyst 15 and bis(4-nitrophenyl)phosphoric acid for the synthesis of cyclic amine is reported. This method was successfully applied for the synthesis of antiplatelet drug clopidogrel.
- Swain, Sharada Prasanna,Shri, Om,Ravichandiran
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- Synthetic hydrosulfuric acid clopidogrel and intermediate of the new method (by machine translation)
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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)
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- A method for the preparation of clopidogrel hydrogen sulfate (by machine translation)
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The invention relates to a method for the preparation of clopidogrel hydrogen sulfate, it to 2 - thiophene acetaldehyde as basic starting material, with their O-chlorobenzene glycine methyl ester condensation reaction, generating the corresponding imine intermediate, then sodium borohydride or directly for the imine intermediate nitrile sodium borohydride reduction to the corresponding secondary amine intermediate, then this kind of secondary amine intermediate ring by reaction with formaldehyde clopidogrel, acidified by sulfuric acid to obtain the target compound of the clopidogrel hydrogen sulfate. The present invention provides a synthetic route of the short, relates to the reaction are classical organic reaction, mild reaction conditions, the operation is simple, the total high yield, low cost, and is suitable for industrial production. (by machine translation)
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Paragraph 0034; 0037; 0043; 0049
(2017/10/06)
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- Chemo-enzymatic approach to the synthesis of the antithrombotic clopidogrel
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The (S)-2-chlorophenylglycine moiety is well recognized in the structure of (S)-clopidogrel, a known antithrombotic drug. We prepared an enantiomerically pure chiral building block via an enzyme-catalyzed resolution of (RS)-N-Boc-2-chlorophenylglycine methylester. The best results were obtained by means of an immobilized subtilisin, the cross-linked enzyme aggregate (Alcalase-CLEA). The high enantiomeric excess of the synthon obtained remained the same over the course of clopidogrel synthesis; the simplicity of the process makes this pathway suitable for large-scale preparation.
- Ferraboschi, Patrizia,Mieri, Maria De,Galimberti, Fiorella
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experimental part
p. 2136 - 2141
(2010/10/03)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF CLOPIDOGREL
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The present invention relates to an improved process for the preparation of Clopidogrel of Formula (I). More particularly, the present invention relates to an improved process for the preparation of Clopidogrel intermediate of formula (III) using triethylamine as an organic base in the absence of an organic solvent. Formula (I), Formula (III).
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Page/Page column 5; 8
(2008/06/13)
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