Preparation method of trelagliptin succinate dimer and application thereof

A technology of troxagliptin succinate and dimer, which is applied in the field of medicine, can solve the problems such as difficult removal of dimer impurities, and achieve the effects of quality control, simple route, and easy control of reaction conditions

Inactive Publication Date: 2020-06-09
北京鑫开元医药科技有限公司
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  • Abstract
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  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Yet in the preparation process of succinate trexagliptin, there will be dimer impurity as shown in formula I to generate, and this dimer impurity is difficult to remove in subsequent succinate trexagliptin refining process, is succinate tregel One of the main impurities in Gliptin quality research

Method used

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  • Preparation method of trelagliptin succinate dimer and application thereof
  • Preparation method of trelagliptin succinate dimer and application thereof
  • Preparation method of trelagliptin succinate dimer and application thereof

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preparation example Construction

[0014] In a first aspect, the embodiment of the present invention provides a method for preparing a trilagliptin succinate dimer, comprising the following steps:

[0015]

[0016] Step S10, prepare the reaction raw material troglitatin succinate;

[0017] In step S20, under solvent-free conditions, the trilagliptin succinate is thermally melted to prepare a trilagliptin succinate dimer.

[0018] In the preparation method of the trilagliptin succinate dimer provided in this example, the trilagliptin succinate is used as the raw material, and the prepared trilagliptin succinate can be directly melted under solvent-free conditions. The reaction proceeds to produce a dimer of trilagliptin succinate. The preparation method has the advantages of simple route, easily controllable reaction conditions, simple process and high purity of the obtained product, and can be applied to the qualitative and quantitative research and detection of related substances of trilagliptin succinate....

Embodiment 1

[0034] In step S1, 50 g (0.105 mol) of the reaction raw material, troxagliptin succinate, was prepared.

[0035] Step S2, add the prepared trilagliptin succinate to the single-neck bottle, stir, heat up to 240° C., heat-melt the trilagliptin succinate, the reaction time is 1h, and the thin-layer chromatography monitoring shows that the trilagliptin succinate is monitored. When less than 20% of tin remained, the reaction was stopped, the reactant was dissolved in dichloromethane, and then concentrated to obtain a yellowish oily substance.

[0036] Mass spectrometry detection of the yellow oily substance was obtained. figure 1 The mass spectrum shown in the figure, the NMR detection of the yellow oily substance was obtained. figure 2 NMR spectrum shown. in figure 2 The results of the NMR spectrum shown are as follows:

[0037] Chemical shift (ppm) hydrogen number 1.38.14～1.622 6 1.6732～1.80 2 2.301.56～2.38 4 2.39～2.43 2 2.70～2.80 2 ...

Embodiment 2

[0043] In step S1, 50 g (0.105 mol) of the reaction raw material, troxagliptin succinate, was prepared.

[0044] Step S2, add the prepared trilagliptin succinate into the single-neck bottle, stir, heat up to 220° C., heat-melt the trilagliptin succinate, the reaction time is 0.5h, and the thin-layer chromatography monitoring shows that the troxagliptin succinate is monitored. When less than 20% of the liptin remained, the reaction was stopped, the reactant was dissolved in dichloromethane, and then concentrated to obtain a crude product of the dimer of trilagliptin succinate. The content measured by high performance liquid chromatography was 84.5%, and the yield was 55.2%.

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Abstract

The invention belongs to the field of medicines, and particularly relates to a preparation method of a trelagliptin succinate dimer and an applicationthereof, and the method comprises the following steps: preparing a reaction raw material trelagliptin succinate; and preparing trelagliptin succinate dimer by thermally melting trelagliptin succinate under a solvent-free condition. According to the technical scheme provided by the invention, the route is simple, the reaction conditions are easy to control, the process is simple, the purity of the obtained product is relatively high, and the method can be applied to qualitative and quantitative research and detection of trelagliptin succinate related substances, and has important significance for effectively controlling the quality of trelagliptin succinate.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a preparation method and application of a succinate trilagliptin dimer. Background technique [0002] Trolagliptin succinate was launched in Japan on March 26, 2015. It is a once-weekly dipeptidyl peptidase IV (DPP-4) inhibitor, which can selectively and persistently inhibit DPP-4. DPP-4 is an enzyme that triggers the inactivation of incretin (glucagon-like peptide-1 (GLP-1)) and glucose-dependent insulinotropic polypeptide (GIP). Inhibition of DPP-4 can increase blood sugar level-dependent insulin secretion, thereby controlling blood sugar levels. [0003] But in the preparation process of succinate succinate, there will be dimer impurity as shown in formula I to generate, and this dimer impurity is not easy to remove in the subsequent succinate succinate refining process, is succinate succinate One of the major impurities in liptin quality studies. Determining a simple an...

Claims

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Application Information

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IPC IPC(8): C07D401/14C07D401/04
CPCC07D401/04C07D401/14
Inventor 芮忠磊于凯王永广孙学涛戴信敏
Owner 北京鑫开元医药科技有限公司
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