Cyclopropanecarboxamide derivative H crystal form and preparation method thereof

A technology of cyclopropanecarboxamide and derivatives, applied in organic chemical methods, drug combinations, pharmaceutical formulations, etc., can solve the problems of unfavorable hygroscopicity and instability of cyclopropanecarboxamide derivatives, and achieve excellent high temperature stability, The effect of good bioavailability

Active Publication Date: 2015-12-30
SHANGHAI SUNTRONG BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The problem to be solved by the present invention is that problems such as instability, hygroscopicity and easy conversion into stable crystal forms of existing cyclopropanecarboxamide derivatives are unfavorable for pharmaceutical processing and use in pharmaceutical compositions. Cyclopropanecarboxamide derivatives The problem of providing more qualitative and quantitative information for the curative effect research of solid drugs

Method used

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  • Cyclopropanecarboxamide derivative H crystal form and preparation method thereof
  • Cyclopropanecarboxamide derivative H crystal form and preparation method thereof
  • Cyclopropanecarboxamide derivative H crystal form and preparation method thereof

Examples

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Effect test

Embodiment 1

[0033] Example 1 Preparation of cyclopropanecarboxamide derivative H crystal form

[0034] Weigh 500 mg of cyclopropanecarboxamide derivative raw materials into a container, add 100 mL of ethanol (analytical grade) and N,N-dimethylformamide (analytical grade) 1:2 mixed solvent, suspend at 35°C for 48 hours, filter , After vacuum drying, a white powder is obtained. The yield was calculated to be 56% by weighing.

Embodiment 2

[0035] Example 2. Characterization of cyclopropanecarboxamide derivative H crystal form by XRPD pattern

[0036] The measurement of X-ray powder diffraction (XRPD) pattern was carried out with RigakuUltimaIV model combined multi-function X-ray diffractometer. The specific information collected is as follows: Cu anode (40kV, 40mA), scanning speed 20° / min, scanning range (2θ range) 3~45°, scanning step 0.02, slit width 0.01. Samples were processed by pressing glass slides directly on the test plate. Subsequent XRPD patterns were all measured in a similar way.

[0037] Determine the XRPD pattern of the cyclopropanecarboxamide derivative H crystal form prepared according to the method described in Example 1, at 2θ=9.341, 13.019, 14.2, 16.66, 17.201, 18.37, 18.901, 20.522, 20.82, 21.141, 21.759, 23.001, There are diffraction peaks at 23.441, 24.461, 25.059, 26, 26.539, 28.8, 29.661, 33.657, such as figure 1 shown. The error range of the 2θ value is ±0.2. After testing, the err...

Embodiment 3

[0039] Example 3. Investigation on the high temperature stability of cyclopropanecarboxamide derivative H crystal form

[0040] The samples of cyclopropanecarboxamide derivative H crystal form were placed in an oven at 60°C, and the samples were taken out for XRPD testing after 5 days and 10 days (such as figure 2 and Figure 5 ) to investigate the crystal stability of the samples against temperature. The results show that the sample of crystal form H is stable at high temperature.

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Abstract

The invention provides a cyclopropanecarboxamide derivative H crystal form (please see the specification for the formula) in the formula (I). According to the XRPD illustration of the crystal form, diffraction peaks exist when 2Q is equal to 9.341, 13.019, 14.2, 16.66, 17.201, 18.37, 18.901, 20.522, 20.82, 21.141, 21.759, 23.001, 23.441, 24.461, 25.059, 26, 26.539, 28.8, 29.661 and 33.657, and the error range of the 2Q value is +/-0.2. The cyclopropanecarboxamide derivative H crystal form has good high-temperature stability, high-humidity stability and illumination stability. Moreover, low moisture absorption performance is achieved. The cyclopropanecarboxamide derivative H crystal form can be applied to drugs for treatment or prevention of JAK-participated inflammation and autoimmunity diseases, proliferative diseases, graft rejective reactions and congenital cartilage deformation or diseases caused by IL6 oversecretion, and good bioavailability is further achieved. Meanwhile, qualitative and quantitative information is provided, which is of important significance to further studying the curative effect of the solid drugs.

Description

technical field [0001] The present invention relates to a polymorphic form of a cyclopropanecarboxamide derivative as a JAK inhibitor, in particular, to a cyclopropanecarboxamide derivative H crystal form and a preparation method thereof. Background technique [0002] JAK, or Janus Kinase, is a non-receptor tyrosine protein kinase and a class of non-transmembrane tyrosine kinases. This is because JAKs can both phosphorylate the cytokine receptors that bind to them and phosphorylate multiple signaling molecules that contain specific SH2 domains. The JAK protein family includes 4 members: JAK1, JAK2, JAK3 and TYK2. They have 7 JAK homology domains (JAKhomology domains, JH) in structure, of which the JH1 domain is a kinase domain, and the JH2 domain is a "pseudo" domain. The kinase domain, JH6 and JH7 are receptor binding domains. [0003] TYK2 is a potential target of immuno-inflammatory diseases, which has been confirmed by human genetics and mouse knockout studies (Levy D....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04A61K31/541A61P37/02A61P29/00A61P35/00A61P37/06A61P19/08
CPCC07B2200/13C07D471/04
Inventor 弋东旭陈金瑶于迎渌
Owner SHANGHAI SUNTRONG BIOTECH
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