2096989-56-7

Usage

Uses

Used in Pharmaceutical Industry:
(1S,2S,3R,5S)-3-(7-((1S,2R)-2-(3,4-difluorophenyl)cyclopropylaMino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyriMidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol is used as an impurity in Ticagrelor (T437700) for [application reason]. Ticagrelor is a medication used to reduce the risk of clot-related events such as heart attack and stroke in patients with acute coronary syndrome or a history of myocardial infarction. The presence of (1S,2S,3R,5S)-3-(7-((1S,2R)-2-(3,4-difluorophenyl)cyclopropylaMino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyriMidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol as an impurity may affect the drug's efficacy, safety, or stability, and thus its study and control are crucial in the pharmaceutical industry.

Upstream product

• 274693-26-4 [3aR-[3aα,4α,6α,(1R,2S),6aα]]-2-[6-[[[7-(2-(3,4-difluorophenyl)cyclopropyl)]amino-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]tetrahydro-2,2-dimethyl-4H-cyclopenteno-1,3-dioxolan-4-yl]oxy]ethanol 
• 220241-60-1 (3aR,4S,6R,6aS)-6-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol 
• 1431867-39-8 4-chloro-6-methoxy-5-nitro-2-(propylthio)pyrimidine 
• 1431867-41-2 (3aR,4S,6R,6aS)-6-((6-methoxy-5-nitro-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol 
• 1431867-42-3 (3aR,4S,6R,6aS)-6-((5-amino-6-methoxy-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol 
• 1431867-43-4 (3aR,4S,6R,6aS)-6-(7-methoxy-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol 
• 1431867-54-7 methyl 2-(((3aR,4S,6R,6aS)-6-(7-methoxy-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)acetate 
• 1431867-57-0 2-(((3aR,4S,6R,6aS)-6-(7-methoxy-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol 
• 220241-59-8 (3aR,4S,6R,6aS)-6-((6-chloro-5-nitro-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol 
• 10257-32-6 D-ribose 
• 1444301-56-7 tert-butyl ((3aS,4R,6S,6aR)-6-(2-(tert-butoxy)ethoxy)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)carbamate 
• 1444301-59-0 (1S,2S,3R,5S)-3-(benzylamino)-5-(2-(benzyloxy)ethoxy)cyclopentane-1,2-diol 
• 1402150-32-6 (1S 2S,3R,5S)-3-[(5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino]-5-(2-hydroxyethoxy)cyclopentane-1,2-diol 
• 1006614-49-8 (1R,2S)-2-(3,4-difluorophenyl)cyclopropanamine 

Downstream Products

• 1251765-07-7 (1S,2S,3R,5S)-3-[7-amino-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-1,2-cyclopentanediol 

Relevant academic research and scientific papers

PROCESS FOR THE PREPARATION OF TICAGRELOR

The present invention relates to a process for the preparation of ticagrelor, which provides a product of high purity, in particular, with no detectable levels of Nnitrosmine impurities. The process comprises a first step of treating 2- [[(3aR,4S,6R,6aS)-6-[[5-amino-6-chloro-2-(propylthio)-4-pyrimidinyl]amino]tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol starting material with sodium nitrite, followed by acidic washing; in a second step, the 2-[[(3aR,4S,6R,6aS)-6-[7-chloro-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]tetrahydro-2,2-dimethyl-4H- cyclopenta-1,3-dioxol-4-yl]oxy]ethanol obtained in the previous step is coupled with trans-(1 fl,2S)-2-(3,4-difluorophenyl)cyclopropylamine, and the reaction is followed by a first washing at basic pH a second washing at acidic pH; and in an third step, the compound obtained in the previous step is deprotected by treatment with mineral acid, followed by acidic washing.

Method for preparing ticagrelor

The present invention discloses a method for preparing ticagrelor. In the method, 4,6-dihalo-5-nitro-2-propylthiopyrimidine (II) as raw materials and a series of reactions of substitution, reduction,ring formation, substitution, deprotection, etc. are conducted to obtain the ticagrelor. The method has cheap and readily available raw materials, simple process conditions, convenient post-processing, high total yield, and is more suitable for industrial production.

Synthesis of ticagrelor analogues belonging to 1,2,3-triazolo[4,5-d]pyrimidines and study of their antiplatelet and antibacterial activity

Based on the recent observation that the antiplatelet agent ticagrelor and one of its metabolite exert bactericidal activity against gram-positive bacteria, a series of 1,2,3-triazolo[4,5-d]pyrimidines structurally related to ticagrelor were synthesized and examined as putative antiplatelet and antibacterial agents. The aim was to assess the possibility of dissociating the two biological properties and to find novel 1,2,3-triazolo[4,5-d]pyrimidines expressing antiplatelet activity and devoid of in vitro antibacterial activity. The new compounds synthesized were known metabolites of ticagrelor as well as structurally simplified analogues. Some of them were found to express antiplatelet activity and to lose the antibacterial activity, supporting the view that the two activities were not necessarily linked.

Production process of ticagrelor fine product

The present invention discloses a production process of a ticagrelor fine product. The process comprises the steps of adopting 4,6-dichloro-5-amino-2-propylthiopyrimidine (IIa) and a compound (IIb) asstarting raw materials, and carrying out five processes including a substitution process I, a cyclization process, a substitution process II, a hydrolysis process and a refining process to finally obtain the ticagrelor fine product. The method provides a ticagrelor production process, uses cheap and easily available raw materials, has the advantages of low production cost, simple reaction conditions, convenient post-treatment, high yield and high product purity, and is more suitable for industrial production.

Synthesis method for ticagrelor

The invention discloses a synthesis method for ticagrelor. The synthesis method comprises the following steps: (a) allowing 6-halogenated-2-propylthio-8-azapurine serving as a raw material to react with (1R,2S)-2-(3,4-difluorophenyl)cyclopropylcarbamic acid tert-butyl ester in alkali and an organic solvent at a room temperature so as to obtain an intermediate (II); (b) dissolving the intermediate(II) and a compound (III) in an organic solvent at a room temperature, and carrying out a reaction under the action of triphenylphosphine and diethyl azodicarboxylate so as to obtain an intermediate (IV); and (c) deprotecting the intermediate (IV) under the action of acid so as to obtain ticagrelor (I). The method provided by the invention has the advantages of cheap and easily-available raw materials, low production cost, short reaction steps, mild reaction conditions, convenient post-treatment and high yield, and is more applicable to industrial production.

Preparation method of platelet aggregation inhibitor ticagrelor

The invention discloses a preparation method of platelet aggregation inhibitor ticagrelor, and belongs to the field of drug synthesis. According to the method, a compound 2 and a compound 3 are used as raw materials, substitution reaction, cyclization reaction, amination reaction and deprotection are sequentially carried out, a crude product is recrystallized by ethyl acetate and normal hexane toobtain the ticagrelor, and the purity of the ticagrelor is up to 99.5% or above. Compared with methods reported in existing literatures, the method has the advantages that the reaction route is obviously shortened, the process stability is high, use of toxic solvents and high-pollution reagents is avoided, and the method is relatively more environmentally friendly and suitable for large-scale production.

Preparation method of amorphous ticagrelor

The invention discloses a preparation method of amorphous ticagrelor, which comprises the steps of preparation of a ticagrelor crude product and preparation of amorphous ticagrelor. The preparation method has the advantages that: 1, a preparation technology of an amorphous ticagrelor product is simple and convenient, mild in technological condition and strong in operability; a single solvent can be used in the reaction for preparing the amorphous product at the same time; the solvent can be recycled for many times; less waste liquid and less pollution are generated; and the production cost islowered by 20-30% as compared with the production cost of the traditional preparation method at the same time; and 2, the solvents used are low boiling point volatile solvents; the product is easy todry to remove the solvents to meet ICH (International Conference on Harmonization) standard requirements in a drying procedure; and large-scale industrial production is facilitated.

Crystal form I of Ticagrelor Fumarateand its preparing method

The present invention relates to: a type I crystal which is a novel crystalline form of ticagrelor fumarate; and a method for manufacturing the same. The type I crystal according to the present invention is very hygroscopic and is very advantageous for storage and distribution, thereby having an advantage that it is also very advantageous for storage and distribution of formulations made by using the same. In addition, the type I crystal according to the present invention exhibits a spherical shape and has a similar size of crystalline, thereby exhibiting very good physical properties to make formulations such as reducing sticking phenomenon during tableting, being easily mixed with other additives, and ensuring a content uniformity. On the other hand, a manufacturing method according to the present invention can manufacture the type I crystal having a high yield and purity with a simple process.COPYRIGHT KIPO 2020

For [...] novel intermediate and its preparation method

The invention discloses a novel intermediate of ticagrelor, i.e., a compound represented by a formula (I), and a preparation method thereof. The preparation method for the compound represented by the formula (I) comprises a step of subjecting a compound represented by a formula (II) or a proper salt of the compound represented by the formula (II) and a compound represented by a formula (III) to a substitution reaction, wherein R in the formulas represents substituted or unsubstituted benzyl and benzoyl groups. The invention further discloses a preparation method for a ticagrelor compound represented by a formula (A) from the novel intermediate, i.e., the compound represented by the formula (I). The method for preparing ticagrelor from the novel intermediate has the advantages of short reaction time, easy and convenient post-treatment, high yield and high product purity.

Ticagrelor preparation method

The invention discloses a ticagrelor preparation method. Compared with existing routes, the method has the advantages of great increase of the reaction yield and great reduction of the production costdue to step shortening and bare hydroxyl group protection.