Crystal form of AHU377 as well as preparation method and application thereof

A crystal form and crystallization technology, which is applied in the field of AHU377 crystal form and its preparation, can solve problems such as cumbersome operation and unfavorable process quality control, and achieve the effects of simplifying the process flow, avoiding the introduction of impurity ions, and good stability

Active Publication Date: 2016-07-13
CRYSTAL PHARMATECH CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The existing process is not only cumbersome to operate, but also introduces a large number of impurity ions, which is not conducive to process quality control

Method used

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  • Crystal form of AHU377 as well as preparation method and application thereof
  • Crystal form of AHU377 as well as preparation method and application thereof
  • Crystal form of AHU377 as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Preparation method of AHU377 crystal form I:

[0075] Dissolve 801.8mg of AHU377 in 5mL of toluene solution, add 5mL of n-heptane, and then place it at 4℃ and stir overnight to get it.

[0076] Table 1 shows the X-ray powder diffraction data of the crystal form I obtained in this example. Its XRPD diagram is like figure 1 , Its DSC graph is like figure 2 , The TGA diagram is as image 3 .

[0077] Table 1

[0078]

[0079]

[0080]

Embodiment 2

[0082] Preparation method of AHU377 crystal form I:

[0083] Dissolve 510 mg of AHU377 (with an initial purity of 98.74%) in 3 mL of toluene solution, gradually add 3 mL of n-heptane after dissolving, add AHU377 crystal form I as a seed crystal during the process, and place it at room temperature (25°C) and stir to obtain . The final crystal form AHU377 has a purity of 99.64%. The preparation of AHU377 crystal form I can play a role in the purification of raw materials. Through the HPLC purity test, it can be found that the purity is increased from 98.74% to 99.64%, and the purification effect is significant.

[0084] The X-ray powder diffraction data of the crystal form obtained in this example is shown in Table 2.

[0085] Table 2

[0086]

[0087]

Embodiment 3

[0089] Preparation method of AHU377 crystal form I:

[0090] Dissolve 2.02g of AHU377 (with an initial purity of 98.74%) in 20mL of toluene solution, and gradually add 10mL of n-heptane after dissolving. During the process, add AHU377 crystal form I as a seed crystal, and place it at room temperature (25°C) and stir. available. The final crystal form AHU377 has a purity of 99.69%.

[0091] Table 3 shows the X-ray powder diffraction data of the crystal form obtained in this example.

[0092] table 3

[0093]

[0094]

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PUM

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Abstract

The invention relates to a crystal form of AHU377 as well as a preparation method and an application thereof. The novel crystal form is good in stability, low in hygroscopicity and remarkable in technological purification effect. The novel crystal form of the compound AHU377 represented in a formula (I) can be applied to preparation of an anti-heart-failure drug.

Description

Technical field [0001] The present invention relates to the field of chemical medicine, in particular to the crystal form of AHU377 and its preparation method and application. Background technique [0002] AHU377, the chemical name is (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester, and its structural formula is as formula (I): [0003] [0004] Patent US5354892A discloses the structure of AHU377 and the preparation method of its sodium salt for the first time; however, the patent does not involve the crystal form of AHU377. [0005] Patent CN102702119A discloses a double-acting compound LCZ696, the structural formula is shown in formula (II). The complex uses AHU377 and valsartan as active ingredients, and the two active ingredients are connected by hydrogen bonds. The patent also discloses the method of using AHU377 or its salt to prepare LCZ696. LCZ696 is clinically proven to be used to treat a variety of cardiovascular and / or renal dise...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C233/47C07C231/24A61K31/216A61K31/41A61P9/04
CPCA61K31/216A61K31/41C07C231/24C07B2200/13C07C233/47A61K2300/00C07D257/04A61P43/00A61P9/04A61K47/542A61K47/545A61K47/55C07C235/74
Inventor 陈敏华张炎锋杨朝惠余姝张晓宇张良
Owner CRYSTAL PHARMATECH CO LTD
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