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Novel intermediate of ticagrelor and method for preparing ticagrelor

A technology of ticagrelor and an intermediate, which is applied in the field of drug synthesis, can solve the problems of low yield, limited application and the like, and achieves the effects of high yield and simple process

Active Publication Date: 2012-10-17
BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In the preparation method, the yield is lower than 30%, and highly toxic and expensive osmium tetroxide (osmium anhydride) needs to be used in the reaction process to catalyze the cis-oxidation of olefins into diols, these unfavorable factors limit the method in actual production Applications

Method used

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  • Novel intermediate of ticagrelor and method for preparing ticagrelor
  • Novel intermediate of ticagrelor and method for preparing ticagrelor
  • Novel intermediate of ticagrelor and method for preparing ticagrelor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1 One end of ethylene glycol is connected to a protecting group, and the other end is connected to a leaving group

[0040] (1) In step a, one end of ethylene glycol is first connected with a protecting group

[0041] Pass step a1:

[0042]

[0043] Dissolve 100g of ethylene glycol in 150ml of DMF, add 219.4g of imidazole (2.0eq, 3.22mol), cool in an ice-salt bath to about 0°C, slowly add 362.8g (1.5eq, 2.42mol) of TBDMSCl in batches, after the addition is complete After stirring at room temperature for 1 h, two products were formed, namely, only one hydroxyl group was protected and two hydroxyl groups were fully protected, of which compound 3-TS accounted for about 40%. The reaction solution was extracted three times with ethyl acetate, and the organic phase was washed three times with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated through a column to obtain 110 g of compound 3-TS with a yield of 39%.

...

Embodiment 4

[0078] The synthesis of embodiment 4 ticagrelor

[0079] Step (a):

[0080]

[0081] Take 42.7g of compound of formula 6 (1.1eq, 0.18mol) 4,6-dichloro-2-(propylsulfanyl)-5-pyrimidinamine and dissolve it in 200ml of ethanol, add 75g of compound 5-1 (1eq, 0.16 mol), then add 125ml triethylamine, keep the temperature between 20~25℃, seal the reactor, raise the temperature to 120~125℃, keep the reaction mixture within the temperature range for 30 hours, then cool to 75℃ °C, release the pressure. Adjust the temperature of the mixture to 50°C, evaporate the solvent under reduced pressure at 30-40°C, add 200ml of ethyl acetate and 300ml of water, adjust the pH of the mixture to 5 with 3M hydrochloric acid solution, and separate the two phases. The organic phase was washed with 15% brine, and the organic phase was concentrated under reduced pressure to obtain compound 7-1.

[0082] Step (b):

[0083]

[0084] Compound 7-1 obtained in the previous step was dissolved in a mi...

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PUM

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Abstract

The invention provides a novel intermediate of ticagrelor or its salt. The novel intermediate is shown in the formula 5. In the formula 5, P1 represents a hydroxyl protecting group. The invention also provides a method for preparing ticagrelor from the novel intermediate shown in the formula 5. The method for preparing ticagrelor from the novel intermediate shown in the formula 5 has the advantages of simple processes, high yield and less three wastes, and can satisfy the demand of industrial production.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to an intermediate of a small molecule anticoagulant drug ticagrelor, a preparation method of the intermediate and a method for preparing ticagrelor by using the intermediate. Background technique [0002] Ticagrelor (Ticagrelor; previously used code: ADZ6140, ARC126532), belongs to the cyclopentyl triazolopyrimidine compound, the chemical name is (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 new type of selective small molecule anticoagulant drug developed by AstraZeneca. The drug can reversibly act on the Purinoceptor 2 receptor (P2Y12) subtype P2Y12 on vascular smooth muscle cells (VSMC), and has obvious inhibitory effect on ADP-induced platelet aggregation, and the effect is rapid after oral administration. Therefore, it can effectively improve the symp...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D317/44C07D407/12C07F7/18C07D487/04
CPCC07D487/04C07D317/44Y02P20/55
Inventor 袁建栋
Owner BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD
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