- Preparation method of phenyl-containing compound
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The present invention discloses a method for preparing an phenyl-containing compound. The present invention provides a method for preparing a compound shown in formula I, comprising the following steps: in the presence of formamide or acetamide, in the pr
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Paragraph 0106-0111
(2022/01/04)
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- Preparation method of ticagrelor key intermediate
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The invention relates to the technical field of medicines, in particular to a preparation method of a ticagrelor key intermediate, which comprises the following steps: dissolving a compound shown as a formula I and 3,4-difluoroiodobenzene in a solvent, adding a catalyst, a first ligand, a second ligand, acid and a metal salt catalyst, and heating for reaction to obtain a compound shown as a formula II; dissolving the compound shown in the formula II and alkali in a solvent, stirring the mixture for reaction, dropwise adding bromine, continuing the reaction after dropwise adding, and adding sodium thiosulfate to generate a compound shown in a formula III after the reaction is finished. The preparation method of the ticagrelor chiral intermediate is short and novel in route, mild in reaction condition, economical and effective, higher in yield compared with an existing preparation method, and suitable for large-scale industrial production.
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Paragraph 0044-0050
(2021/05/29)
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- Preparation method of ticagrelor key intermediate
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The invention belongs to the technical field of medicines, and particularly relates to a preparation method of a ticagrelor key intermediate, and the method is used for preparing the ticagrelor intermediate, has the advantages of short reaction steps, mild reaction conditions and higher yield than the existing preparation method, is economical and effective, and is suitable for large-scale industrial production.
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Paragraph 0013
(2020/05/08)
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- Method for synthesizing (1R,2R)-2-(3,4-difluorophenyl)cyclopropane-carboxylic acid
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The invention discloses a method for synthesizing a compound, i.e., (1R,2R)-2-(3,4-difluorophenyl)cyclopropane-carboxylic acid. A synthesis route is shown as follows. The compound represented by a formula I shown in the description is synthesized through
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Paragraph 0025-0049
(2019/06/05)
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- Ticagrelor key intermediate and preparation method thereof
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The invention discloses a ticagrelor key intermediate 1-TK-acid and a preparation method of the ticagrelor key intermediate 1-TK-acid. The ticagrelor key intermediate has a structure shown in a formula (D) which is shown in the description. The method comprises the following steps of (1) preparing 2-chloro-1-(3,4-difluorophenyl)ethanone; (2) preparing a methylbenzene solution of 2-chloro-1-S-(3,4-difluorophenyl)ethyl alcohol; (3) preparing the ticagrelor key intermediate 1-TK-acid. The ticagrelor key intermediate 1-TK-acid has the advantages that the technology is matured and stable, the product quality is stable, the production technology is safe and reliable, and the ticagrelor key intermediate 1-TK-acid is suitable for industrialized production.
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Paragraph 0020; 0032-0036; 0053; 0070
(2018/05/16)
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- Preparation method of ticagrelor
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The invention discloses a preparation method of ticagrelor. The preparation method comprises the following steps: (1) preparation of ticagrelor intermediate product 1-TK acid; (2) preparation of ticagrelor intermediate product 2-TK-amide; (3) preparation of ticagrelor intermediate product 3-TK-amino compound hydrochloride; (4) preparation of ticagrelor intermediate product 4-TK-amino compound R-tartrate; ( 5) preparation of ticagrelor intermediate product 5-TK-amino compound L-mandelate; and (6) preparation of ticagrelor-TK. The preparation method has the advantages of cost advantage, mature and stable process, stable product quality, and safe and reliable production process.
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- Ticagrelor intermediate, and preparation method thereof
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The invention belongs to the technical field of drug synthesis, and relates to a ticagrelor intermediate, and a preparation method thereof. The ticagrelor intermediate can be prepared conveniently via following steps: (E)-3-(3,4-difluorophenyl) propenal a
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Paragraph 0065; 0066
(2017/10/20)
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- for standard auspicious Luo river intermediate preparation method
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The inventiondiscloses a preparation method of ticagrelor. The method comprises the following steps: (1) reducing a compound shown in a formula III in the presence of a proton source provided by sodium borohydride or potassium borohydride and diethyl aniline hydrochloride to obtain a compound shown in a formula IV; (2) reacting the compound IV in the presence of alkali to generate a compound VI; (3) hydrolyzing the compound VI without purification to generate a compound VII; (4) reacting the compound VII to generate acyl chloride, reacting the acyl chloride to generate formamide, thus obtaining a compound shown in a formula IX; and (5) carrying out Hofmann rearrangement on the compound IX to obtain a compound shown in a formula II. Regents used in the method are nontoxic, harmless, environmentally friendly and low in price; the used key reagents can be recycled. Therefore, the method is applicable to industrial production.
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Paragraph 0066; 0067; 0068; 0069; 0070; 0071; 0072-0081
(2017/08/25)
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- Comparison of a Batch and Flow Approach for the Lipase-Catalyzed Resolution of a Cyclopropanecarboxylate Ester, A Key Building Block for the Synthesis of Ticagrelor
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In this study a batch reactor process is compared to a flow chemistry approach for lipase-catalyzed resolution of the cyclopropanecarboxylate ester (±)-3. (1R,2R)-3 is a precursor of the amine (1R,2S)-2 which is a key building block of the API ticagrelor. For both flow and batch operation, the biocatalyst could be recycled several times, whereas in the case of the flow process the reaction time was significantly reduced.
- Hugentobler, Katharina G.,Rasparini, Marcello,Thompson, Lisa A.,Jolley, Katherine E.,Blacker, A. John,Turner, Nicholas J.
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p. 195 - 199
(2017/02/26)
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- PREPARATION OF TICAGRELOR
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Provided are processes for preparing Ticagrelor and its intermediates that are useful in the processes. Also provided are salts of Ticagrelor, their processes and solid dispersion of Ticagrelor having Ticagrelor in amorphous form.
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Paragraph 0205
(2015/03/16)
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- NOVEL PROCESSES FOR THE PREPARATION OF PHENYLCYCLOPROPYLAMINE DERIVATIVES AND USE THEREOF FOR PREPARING TICAGRELOR
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Provided herein are novel processes for the preparation of phenylcyclopropylamine derivatives, which are useful intermediates in the preparation of triazolo[4,5-d]pyrimidine compounds. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of a substantially pure ticagrelor intermediate, trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine. Provided further herein are novel acid addition salts of trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine, and process for their preparation. The intermediate and its acid addition salts are useful for preparing ticagrelor, or a pharmaceutically acceptable salt thereof, in high yield and purity.
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- Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents
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Ticagrelor (1) is the first reversible P2Y12 receptor antagonist blocking adenine diphosphate (ADP)-induced platelet aggregation with rapid onset and offset of effects. In this study, synthesis of ticagrelor and its derivatives has been accomplished in a convergent way. The compound design was based on modifications of ticagrelor and its major metabolite (33) in order to ameliorate their pharmacokinetic properties and dosing profile. The final compounds (1a-g, 35a-g) were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. The assay results showed that some compounds (e.g., 1b, 1d, 33, 35b, 35f) exhibited comparable potency with that of ticagrelor.
- Zhang, Hao,Liu, Jun,Zhang, Luyong,Kong, Lingyi,Yao, Hequan,Sun, Hongbin
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p. 3598 - 3602
(2012/07/14)
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- NOVEL PROCESSES FOR THE PREPARATION OF PHENYLCYCLOPROPYLAMINE DERIVATIVES AND USE THEREOF FOR PREPARING TICAGRELOR
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Provided herein are novel processes for the preparation of phenylcyclopropylamine derivatives, which are useful intermediates in the preparation of triazolo[4,5-d]pyrimidine compounds. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of a substantially pure ticagrelor intermediate, trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine. Provided further herein are novel acid addition salts of trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine, and process for their preparation. The intermediate and its acid addition salts are useful for preparing ticagrelor, or a pharmaceutically acceptable salt thereof, in high yield and purity.
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- CYCLOPROPYL MODULATORS OF P2Y12 RECEPTOR
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The present invention relates to new cyclopropyl modulators of P2Y12 receptor activity, pharmaceutical compositions thereof, and methods of use thereof.
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- A PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE CYCLOPROPYLAMINES
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This invention relates to a process for the production of optically active 2-(disubstituted aryl) cyclopropylamine derivatives and optically active 2-(disubstituted aryl) cyclopropane carboxamide derivative which are useful intermediates for the preparati
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Page/Page column 30-31
(2008/06/13)
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- From ATP to AZD6140: The discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis
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Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y12 receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side chain and the purine core and investigation of hydrophobic substituents led to a series of neutral molecules. The leading compound, 17 (AZD6140), is currently in a large phase III clinical trial for the treatment of acute coronary syndromes and prevention of thromboembolic clinical sequelae.
- Springthorpe, Brian,Bailey, Andrew,Barton, Patrick,Birkinshaw, Timothy N.,Bonnert, Roger V.,Brown, Roger C.,Chapman, David,Dixon, John,Guile, Simon D.,Humphries, Robert G.,Hunt, Simon F.,Ince, Francis,Ingall, Anthony H.,Kirk, Ian P.,Leeson, Paul D.,Leff, Paul,Lewis, Richard J.,Martin, Barrie P.,McGinnity, Dermot F.,Mortimore, Michael P.,Paine, Stuart W.,Pairaudeau, Garry,Patel, Anil,Rigby, Aaron J.,Riley, Robert J.,Teobald, Barry J.,Tomlinson, Wendy,Webborn, Peter J.H.,Willis, Paul A.
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p. 6013 - 6018
(2008/04/02)
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- Process for the preparation of cyclopropyl carboxylic acid esters and derivatives
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The invention relates to a novel process for the preparation of certain cyclopropyl carboxylic acid esters and other cyclopropyl carboxylic acid derivatives; a novel process for the preparation of dimethylsulfoxonium methylide and dimethylsulfonium methylide; to the use of certain cyclopropyl carboxylic acid esters in a process for the preparation of intermediates that can be used in the synthesis of pharmaceutically active entities; and to certain intermediates provided by these processes.
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- Triazolo(4,5-d)pyrimidine compounds
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Triazolo[4,5-d]pyrimidine compounds are provided of the formula (I) wherein R1, R2, R3, R4, R5and R6are as defined in the specification. Compositions containing the compounds are also provided, together with processes for their preparation and methods of use in the treatment of diseases, including myocardial infarction and unstable angina.
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