866551-95-3

Usage

Uses

Used in Pharmaceutical Industry:
Acetic acid, [[(3aR,4S,6R,6aS)-tetrahydro-2,2-diMethyl-6-[[(phenylMethoxy)carbonyl]aMino]-4H-cyclopenta-1,3-dioxol-4-yl]oxy]-, ethyl ester is used as a reactant in the synthesis of Ticagrelor (T437700), a platelet aggregation inhibitor. Ticagrelor is a medication used to reduce the risk of heart attack, stroke, and other cardiovascular events in patients with acute coronary syndrome or a history of myocardial infarction. Acetic acid, [[(3aR,4S,6R,6aS)-tetrahydro-2,2-diMethyl-6-[[(phenylMethoxy)carbonyl]aMino]-4H-cyclopenta-1,3-dioxol-4-yl]oxy]-, ethyl ester plays a crucial role in the production of this life-saving drug, contributing to its effectiveness in preventing blood clot formation and improving cardiovascular health.

Upstream product

• 155899-66-4 (3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol 
• 501-53-1 benzyl chloroformate 
• 105-36-2 ethyl bromoacetate 
• 60410-16-4 (1R,4S)-4-hydroxy-2-cyclopentene-1-yl acetate 
• 188434-69-7 (1R,4S)-4-(benzyloxy)cyclopent-2-en-1-yl acetate 
• 1423769-48-5 benzyl ((3aS,4R,6aS)-2,2-dimethyl-6-oxotetrahydro-4H-cyclopenta[d][1,3]dioxol-4-yl)carbamate 
• 274693-53-7 [3aS-(3aα,4α,6α,6aα)]-(tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl)carbamic acid phenylmethyl ester 
• 1423769-49-6 benzyl ((3aS,4R,6R,6aR)-6-hydroxy-2,2-dimethyltetrahydro-4H-cyclopenta[d][1,3]dioxol-4-yl)carbamate 
• 38838-06-1 methyl 5-deoxy-5-iodo-2,3-isopropylidene-β-D-ribofuranoside 
• 4137-56-8 methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside 
• 4099-85-8 ((3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol 
• 36468-53-8 β-D-ribofuranose 
• 50600-40-3 (3aS,4S,6aR)-4-(iodomethyl)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole 
• 155855-51-9 tetrahydro-2,2-dimethyl-6-phenylmethyl-(3aS,4S,7R,7aS)-4,7-methano-4H-1,3-dioxolo[4,5-d][1,2]oxazine 

Downstream Products

• 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 

Relevant academic research and scientific papers

Synthesis of an all-cis intermediate of ticagrelor

A six step conversion of the common carbocyclic nucleoside precursor 8 into the all-cis key intermediate for the synthesis of ticagrelor analogs is reported. The method involves two oxidation/stereoselective reduction sequences for both the C-O and C-N bonds. Inversion of stereochemistry was confirmed by analysis of spin couplings between the hydrogens at the junction of the 1,3-dioxolane and cyclopentane rings.

Stereoselective Synthesis for Potential Isomers of Ticagrelor Key Starting Material

Tartrate salt of carbocyclic amine 2 is one of the key starting materials for the synthesis of Ticagrelor 1. During the synthesis of 1, the isomers of 2 also need to be considered as potential impurities and characterized before establishing the specification of product. In the present work, detailed study has been carried out to synthesize the related substances of 2, and their structure characterization has been discussed.

Method for preparing ticagrelor key intermediate

The invention relates to a chemical synthesis method of ticagrelor key intermediate 2-[[(3aR, 4S, 6R, 6aS)-6-aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxolane-4-yl] oxy]ethanol (a key intermediate A). The method comprises the following steps: taking D-ribose as a raw material, and carrying out ten chemical reaction steps of 1-locus methylation and 2,3-loci isopropylidene protection, 4-locus derivatization, iodination, furan ring-opening, hydroxylamine reaction, palladium on carbon catalytic hydrogenation, amino Cbz protection, hydroxy protection, sodium borohydride reduction ester, Cbz removal protection and the like, thereby obtaining the key intermediate A. The raw materials are cheap and readily available, the preparation process is high in operability, steps of optical resolution, chiral induction and the like are avoided, the total yield is relatively high, and the product quality is better; particularly due to the use of sodium borohydride reduction ester, the preparation cost of ticagrelor is greatly reduced; and the method is suitable for large-scale industrial production.

Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents

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.

NEW INTERMEDIATES AND PROCESSES FOR PREPARING TICAGRELOR

The present invention is related to new intermediates and processes for preparing Ticagrelor disclosed in this patent application.

CYCLOPROPYL MODULATORS OF P2Y12 RECEPTOR

The present invention relates to new cyclopropyl modulators of P2Y12 receptor activity, pharmaceutical compositions thereof, and methods of use thereof.

From ATP to AZD6140: The discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis

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.

CHEMICAL PROCESS

The present invention provides a process for the preparation of a compound of formula (I): wherein R1 is C1-6 alkyl; R2 and R3 are, independently, C1-6 alkyl; and R4 is C1-6 alky