Cyclopropanecarboxamide derivative G crystal form and preparation method thereof

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

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

Examples

Experimental program
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Effect test

Embodiment 1 to 13

[0034] Preparation of Crystal Form G of Cyclopropanecarboxamide Derivatives from Examples 1 to 13

[0035] Weigh 500 mg of the cyclopropanecarboxamide derivative raw material in a container, add 2 mL of dimethyl sulfoxide to dissolve it completely, slowly add the solvents (analytical grade) in Table 1 until solids are precipitated, and let stand at room temperature for 12 hours. After filtration and vacuum drying, off-white powder was obtained. Weigh to calculate its yield.

[0036] Table 1 Preparation of cyclopropanecarboxamide derivative G crystal form

[0037] Example

Embodiment 14

[0038] Example 14. Characterization of cyclopropanecarboxamide derivative G crystal form by XRPD pattern

[0039] The measurement of the X-ray powder diffraction (XRPD) pattern is carried out using the RigakuUltimaIV model combined multifunctional X-ray diffractometer, and the specific collection information is as follows: Cu anode (40kV, 40mA), scanning speed 20° / min, scanning range (2θ range) 3~45°, scan step size 0.02, slit width 0.01. Samples were processed using glass slides pressed directly onto the test plate. Subsequent XRPD patterns all adopt similar measurement methods.

[0040]Determination of the XRPD spectrum of the cyclopropanecarboxamide derivative G crystal form prepared according to the method described in Example 1, at 2θ=8.376, 9.76, 10.5, 12.402, 13.362, 14.081, 14.958, 17.16, 17.758, 19.358, 21.579, 22.34, There are diffraction peaks at 22.981, 23.241, 24.459, 24.919, 25.443, 26.7, 27.419, 27.818, 28.378, 29.461, 31.001, 33.56, 34.5, and 35.58, such as ...

Embodiment 15

[0042] Example 15. Investigation of High Temperature Stability of Form G of Cyclopropanecarboxamide Derivatives

[0043] Cyclopropanecarboxamide derivative G crystal form samples were placed in a 60°C oven, and the samples were taken out after 5 days and 10 days for XRPD testing (such as figure 2 with Figure 5 Shown), in order to investigate the stability of the crystal form of the sample to temperature. The results show that the crystal form G sample is stable under high temperature conditions.

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Abstract

The invention provides a cyclopropanecarboxamide derivative G 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 8.376, 9.76, 10.5, 12.402, 13.362, 14.081, 14.958, 17.16, 17.758, 19.358, 21.579, 22.34, 22.981, 23.241, 24.459, 24.919, 25.443, 26.7, 27.419, 27.818, 28.378, 29.461, 31.001, 33.56, 34.5 and 35.58, and the error range of the 2Q value is +/-0.2. The cyclopropanecarboxamide derivative G crystal form has good high-temperature stability, high-humidity stability and illumination stability. Moreover, excellent solubility is achieved. The cyclopropanecarboxamide derivative G 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 invention relates to a polymorphic form of a cyclopropanecarboxamide derivative as a JAK inhibitor, in particular to a crystal form G of a cyclopropanecarboxamide derivative and a preparation method thereof. Background technique [0002] JAK is Janus Kinase, which is a non-receptor tyrosine protein kinase and a non-transmembrane tyrosine kinase. This is because JAK can not only phosphorylate the cytokine receptors associated with it, but also phosphorylate multiple signaling molecules containing specific SH2 domains. The JAK protein family includes 4 members: JAK1, JAK2, JAK3 and TYK2, which have 7 JAK homology domains (JAKhomology domain, JH) in their structure, of which the JH1 domain is the kinase domain and the JH2 domain is the "false" The kinase domain, JH6 and JH7 are receptor binding domains. [0003] TYK2 is a potential target for immunoinflammatory 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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