Method for synthesizing ticagrelor intermediate by micro-channel reactor

A technology of microchannel reactors and channel reactors, applied in chemical instruments and methods, chemical/physical/physical chemical reactors, chemical/physical/physical chemical processes, etc., can solve low yield, low purity, exothermic Uncontrollable problems, to achieve the effect of increased purity and yield, reduced impurity content, and improved safety

Inactive Publication Date: 2020-08-25
HEILONGJIANG XINCHUANG BIOLOGICAL TECH DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] In order to solve the problems of low yield, low purity and uncontrollable exotherm in the synthesis of the intermediate in traditional stirred reactors, the present invention provides an intrinsically safe and environmentally friendly method for synthesi

Method used

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Embodiment 1

[0033] Embodiment 1: the method for synthesizing ticagrelor intermediate in microchannel reactor.

[0034] The present embodiment provides a kind of method that microchannel reactor synthesizes ticagrelor intermediate, such as figure 1 and figure 2As shown, the microchannel reactor adopted includes a preheating module, a premixing module, a reaction module group and a quenching module, wherein: the preheating module is connected in series with the reaction module group, the premixing module is connected in series with the reaction module group, and the reaction module group connected in series with the quenching module.

[0035] 1). Weigh the raw material (3aR,4S,6R,6aS)-6-aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxolane-4- 300 g of alcohol was dissolved in 5 L of tetrahydrofuran to form material I, which was transported to the pre-mixing module of the microchannel reactor for preheating and mixing.

[0036] 2). Take 220g of sodium carbonate and dissolve it in 5L o...

Embodiment 2

[0039] Embodiment 2: the method for synthesizing ticagrelor intermediate in microchannel reactor.

[0040] This embodiment provides a kind of method that microchannel reactor synthesizes ticagrelor intermediate, such as figure 1 and figure 2 As shown, the microchannel reactor adopted includes a preheating module, a premixing module, a reaction module group and a quenching module, wherein: the preheating module is connected in series with the reaction module group, the premixing module is connected in series with the reaction module group, and the reaction module group connected in series with the quenching module.

[0041] 1). Weigh the raw material (3aR,4S,6R,6aS)-6-aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxolane-4- Alcohol 260g is dissolved in the acetonitrile of 3.5L to form material I, and material I is delivered to preheating and mixing in the premixing module of microchannel reactor;

[0042] 2). Weigh potassium carbonate 310g and dissolve it in 5L of water ...

Embodiment 3

[0045] Embodiment 3: the method for synthesizing ticagrelor intermediate in microchannel reactor.

[0046] This embodiment provides a kind of method that microchannel reactor synthesizes ticagrelor intermediate, such as figure 1 and figure 2 As shown, the microchannel reactor adopted includes a preheating module, a premixing module, a reaction module group and a quenching module, wherein: the preheating module is connected in series with the reaction module group, the premixing module is connected in series with the reaction module group, and the reaction module group connected in series with the quenching module.

[0047] 1). Weigh the raw material (3aR,4S,6R,6aS)-6-aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxolane-4- 280g of alcohol is dissolved in 4.2L of tetrahydrofuran to form material I, and material I is transported to the pre-mixing module of the microchannel reactor for preheating and mixing;

[0048] 2). Weigh 172g of sodium carbonate and dissolve it in 4....

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Abstract

The invention discloses a method for synthesizing a ticagrelor intermediate through a micro-channel reactor, and belongs to the technical field of cardiovascular and cerebrovascular drug synthesis. The invention aims to solve the problems of low yield, low purity, uncontrollable heat release and the like in the synthesis of an intermediate in a traditional stirring reaction kettle. The method forsynthesizing the ticagrelor intermediate comprises the following steps of: mixing a precursor (3aR, 4S, 6R, 6aS)-6-aminotetrahydro-2, 2-dimethyl-4H-cyclopentene-1, 3-dioxolane-4-ol with an organic solvent to obtain a material I; dissolving alkali required by the reaction in water to obtain a material II; and dissolving benzyl chloroformate in an organic solvent to obtain a material III, preheatingthe materials, conveying the preheated materials to the reaction module group of a micro-channel reactor, carrying out a reaction, and carrying out post-treatment on a reaction product to obtain theticagrelor intermediate. The method has the advantages of short reaction time and greatly improved safety, and is suitable for industrial production of the ticagrelor intermediate.

Description

technical field [0001] The invention belongs to the technical field of synthesis of cardiovascular and cerebrovascular drugs in organic synthesis, and in particular relates to a method for synthesizing ticagrelor intermediates in a microchannel reactor. Background technique [0002] Ticagrelor, also known as ticagrelor, has a chemical name of (1S,2S,3R,5S)-3-[7-[[(1R,2S)-2-(3,4-difluorophenyl)cyclopropane Base]amino]-5-propylthiotriazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-1,2-cyclopentanediol. It is a new type of cyclopentyltriazole pyrimidine (CPTP) oral antiplatelet drug, which is a non-prodrug and can take effect directly without being activated by liver metabolism. Its chemical structure is as follows: [0003] [0004] From the perspective of chemical synthesis, ticagrelor is divided into three fragments, five-membered ring structure, pyrimidine ring structure, and three-membered ring structure. Among the many reported synthetic routes of ticagrelor, its chi...

Claims

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Application Information

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IPC IPC(8): C07D317/44B01J19/00
CPCB01J19/0093C07D317/44
Inventor 任吉秋
Owner HEILONGJIANG XINCHUANG BIOLOGICAL TECH DEV CO LTD
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