Preparation method of Ticagrelor intermediate

A technology for ticagrelor and intermediates, which is applied in the field of preparation of ticagrelor intermediates, can solve the problems of unsuitability for large-scale industrial production, column purification of products, and many side reactions, and achieve high product yields and excellent reaction conditions. Gentle and easy to control, easy to operate effect
CN102796007AActive Publication Date: 2012-11-28JINAN RUIFENG PHARMA +2
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
JINAN RUIFENG PHARMA
Publication Date
2012-11-28

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Abstract

The invention relates to the medicine chemical synthesis field, and especially discloses a preparation method of a Ticagrelor intermediate. The preparation method comprises the following steps: 1) taking 3,4-difluorobenzaldehyde (I) as an initial raw material, reacting with a phosphorus ylide material liquid to obtain (E)-3-(3,4-difluorophenyl)-2-acrylic acid ester (II); 2) performing a Simons-Smith asymmetric cyproteronethe reaction on the (E)-3-(3,4-difluorophenyl)-2-acrylic acid ester (II) to obtain trans-(1R,2R)-2-(3,4-difluorophenyl) cyclopropanecarboxylic acid ester (III); 3) performing aminolysis on the trans-(1R,2R)-2-(3,4-difluorophenyl) cyclopropanecarboxylic acid ester to obtain trans-(1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarboxamide (IV); and 4) performing a Huffman rearrangement reaction on the trans-(1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarboxamide (IV) to obatain the Ticagrelor intermediate (V). The method of the invention has the advantages of simple process, convenient operation, mild reaction condition and easy control, low cost and easy acquisition of raw material, high product yield and product purity, and is adapted to large scale industrial production.
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Description

(1) Technical field

[0001] The invention relates to the field of pharmaceutical chemical synthesis, in particular to a preparation method of a ticagrelor intermediate. (2) Background technology

[0002] Ticagrelor, English name ticagrelor, chemical name (1S, 2S, 3R, 5s)-3-[7-[(1R, 2S)-2-(3,4-difluorophenyl) cyclopropylamino]- 5-(thiopropyl)-3H-[1,2,3]triazol[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1,2 -diol is a novel, selective small molecule anticoagulant drug developed by AstraZeneca. The drug has obvious inhibitory effect on platelet aggregation caused by ADP, and the effect is rapid after oral administration, so it can effectively improve the symptoms of patients with acute coronary heart disease.

[0003] Trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine is an important intermediate for the synthesis of ticagrelor, and its structural formula is

[0004]

[0005] The preparation method of currently announced trans-(1R, 2S)-2-(3,4-difluorophenyl)-...

Claims

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