Preparation method of eptifibatide impurity I

A technology for eptifibatide and impurities, which is applied in the field of preparation of eptifibatide impurity I, can solve the problems of no relevant literature reports on the preparation of impurity I, etc., and achieve high purity and yield, low cost, and easy industrial production Effect

Pending Publication Date: 2022-07-01
HYBIO PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] There are a large number of existing literature reports on the method for preparing ep

Method used

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  • Preparation method of eptifibatide impurity I
  • Preparation method of eptifibatide impurity I
  • Preparation method of eptifibatide impurity I

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Example Embodiment

[0041] The invention provides a preparation method of eptifibatide impurity I. Those skilled in the art can learn from the content of this document and appropriately improve the process parameters to achieve. It should be particularly pointed out that all similar substitutions and modifications are obvious to those skilled in the art, and they are deemed to be included in the present invention. The method and application of the present invention have been described through the preferred embodiments, and it is obvious that relevant persons can make changes or appropriate changes and combinations of the methods and applications herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention. Invention technology.

[0042] The test materials used in the present invention are all common commercial products and can be purchased in the market.

[0043] The invention provides a method for the preparation of eptifibatid...

Example Embodiment

[0062] Example 1 Synthesis of Compound 1

[0063] 2-Cl-Trt resin (85.7 g, Sub=1.4 mmol / g) was weighed into the solid-phase reaction column, washed twice with DMF, swollen with DMF for 30 minutes, and the solution was removed. Weigh Fmoc-Pro-OH 81.0g (240mmol), DIPEA125.7mL (480mmol) and 300ml DMF, add it to the reaction column, react at room temperature for 2 hours, then add 50mL methanol, react at room temperature for 1 hour, extract the solution, DMF Wash three times. A 20% piperidine solution was added to remove the Fmoc protecting group, the reaction was stirred at room temperature for 5 minutes, the solution was removed, the operation was repeated once, and the DMF was washed six times.

[0064] Weigh Boc-Trp(Boc)-OH 97.1 g (240 mmol), PyBOP 124.9 g (240 mmol), HOBt 38.9 g (288 mmol) and 300 ml DMF, slowly add DIPEA 125.7 mL (480 mmol) under ice bath for activation, then add the solution to In the reaction column, the reaction was carried out at room temperature for 2 h...

Example Embodiment

[0066] Example 2 Synthesis of Compound 2

[0067] Weigh compound 1 (59.6g, 118mmol), 23.65g (178mmol) of 2-bromoacetophenone and 600ml of ethyl acetate into a glass bottle, add 75ml of triethylamine (535mmol) under ice bath, react at room temperature overnight, and monitor by TLC reaction. After the completion of the reaction of compound 1, it was washed with 10% citric acid solution, saturated sodium bicarbonate solution and saturated sodium chloride solution in turn, and the organic phase was concentrated to dryness under reduced pressure, and purified by silica gel column chromatography to obtain compound 2 (59 g). Mass spectrometry see figure figure 2 , which is consistent with the theory.

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Abstract

The invention relates to the technical field of polypeptides, in particular to a preparation method of an eptifibatide impurity I. According to the preparation process, the purity and the yield of the eptifibatide impurity I are relatively high, the synthesis route is simple, the controllability is good, the cost is relatively low, and industrial production is easy to realize. Experiments show that the total yield of the eptifibatide impurity I obtained through the preparation method reaches 56%, and the purity is 98% or above.

Description

technical field [0001] The invention relates to the technical field of polypeptides, in particular to a preparation method of eptifibatide impurity I. Background technique [0002] Eptifibatide is a cyclic heptapeptide found in the venom of the dwarf rattlesnake, which can selectively block the binding of glycoprotein IIb / IIIa to adhesion proteins, and has a certain weak inhibitory effect on adhesion-related receptors. , At low concentrations, it can prevent platelet aggregation caused by adenosine diphosphate and epinephrine. Clinically, it is mainly used for acute coronary syndrome and percutaneous coronary intervention. Its peptide sequence is as follows: [0003] [0004] Impurity I is generated during the preparation and storage of eptifibatide, which affects the safety of the drug. In the process of developing the eptifibatide production process, it is necessary to prepare a reference substance of impurity I for the study of its product quality. The structure of...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K1/16C07K1/06C07K1/04
CPCC07K7/06
Inventor 汪伟姜绪邦尹传龙唐洋明余品香
Owner HYBIO PHARMA
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