CN112830930A

CN112830930A - Crystal form of EOC317 and preparation method and application thereof

Info

Publication number: CN112830930A
Application number: CN202011509384.1A
Authority: CN
Inventors: 李合亭; 于洪瑞; 迪帕克·海格德; 邹晓明
Original assignee: Taizhou Yiteng Jingang Pharmaceutical Co ltd
Current assignee: Taizhou Yiteng Jingang Pharmaceutical Co ltd
Priority date: 2020-12-18
Filing date: 2020-12-18
Publication date: 2021-05-25
Anticipated expiration: 2040-12-18
Also published as: CN112830930B

Abstract

The present application relates to polymorphic forms of the compound N- {4- [ 4-amino-6- (methoxymethyl) -7- (morpholin-4-ylmethyl) pyrrolo [2,1-f ] [1,2,4] triazin-5-yl ] -2-fluorophenyl } -N' - [ 2-fluoro-5- (trifluoromethyl) phenyl ] urea, or a hydrate thereof, and processes for the preparation thereof, use thereof, and pharmaceutical compositions comprising the polymorphic forms, which polymorphic forms or pharmaceutical compositions are useful for the treatment of cancer.

Description

Crystal form of EOC317 and preparation method and application thereof

Technical Field

The application relates to the field of biomedicine, in particular to a polymorphic form of a compound N- {4- [ 4-amino-6- (methoxymethyl) -7- (morpholin-4-ylmethyl) pyrrolo [2,1-f ] [1,2,4] triazin-5-yl ] -2-fluorophenyl } -N' - [ 2-fluoro-5- (trifluoromethyl) phenyl ] urea or a hydrate thereof, and a preparation method, application and a pharmaceutical composition containing the polymorphic form.

Background

N- {4- [ 4-amino-6- (methoxymethyl) -7- (morpholin-4-ylmethyl) pyrrolo [2,1-f ] [1,2,4] triazin-5-yl ] -2-fluorophenyl } -N' - [ 2-fluoro-5- (trifluoromethyl) phenyl ] urea (CAS No.:939805-30-8, also known as EOC317) is a novel kinase inhibitor having the structure of formula I,

the EOC317 can target cancer cells through various action mechanisms, has good performance in preclinical experiments and toxicology experiments, and has the potential of becoming a latest generation of anticancer drugs with targeting effect. At present, no public report on the crystal form of the EOC317 compound exists.

Disclosure of Invention

It is an object of the present application to provide polymorphic forms of N- {4- [ 4-amino-6- (methoxymethyl) -7- (morpholin-4-ylmethyl) pyrrolo [2,1-f ] [1,2,4] triazin-5-yl ] -2-fluorophenyl } -N' - [ 2-fluoro-5- (trifluoromethyl) phenyl ] urea and hydrates thereof. The three crystal forms prepared by the method can be identified and distinguished from other crystal forms by means of characteristic X-ray powder diffraction (XRPD) patterns, DSC curves, TGA curves, Fourier transform-infrared spectroscopy (FT-IR spectra) and the like. Through the property research of the crystal forms, the crystal forms are found to have good stability, lower hygroscopicity, better solubility and excellent in-vivo metabolic dynamics properties, and have good absorption after oral administration, higher exposure, ideal half-life and better development prospect.

It is another object of the present application to provide a pharmaceutical composition comprising the above polymorph.

It is another object of the present application to provide the use of the above polymorph or pharmaceutical composition for the manufacture of a medicament for the treatment of cancer.

In one aspect, the present application provides a crystalline form a of a compound of formula I,

the form A shows characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., and 18.1 + -0.2 deg. in an X-ray powder diffraction pattern expressed by a diffraction angle 2 theta angle obtained using Cu-Ka radiation.

In certain embodiments, the form a further exhibits a characteristic peak at least one of 2 Θ angles selected from 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 ° in an X-ray powder diffraction pattern expressed in diffraction angle 2 Θ angles obtained using Cu-K α radiation.

In certain embodiments, the form a further exhibits a characteristic peak at least one of 2 Θ angles selected from 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 ° in an X-ray powder diffraction pattern expressed in diffraction angle 2 Θ angles obtained using Cu-K α radiation.

In certain embodiments, the form a further exhibits a characteristic peak at least one of 2 Θ angles selected from 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 ° in an X-ray powder diffraction pattern expressed in diffraction angle 2 Θ angles obtained using Cu-K α radiation.

In certain embodiments, the form a further exhibits a characteristic peak at least one of 2 Θ angles selected from 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 °, and 27.4 ± 0.2 ° in an X-ray powder diffraction pattern expressed in diffraction angle 2 Θ angles obtained using Cu-K α radiation.

In another aspect, the present application provides a crystalline form a of the compound of formula I,

in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A is 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

In certain embodiments, the form a is further selected from 2871 ± 2cm in an infrared spectrum obtained by infrared spectroscopic characterization^-1，2806±2cm^-1And 3104 + -2 cm^-1At least one of the wavenumbers of (a) shows a characteristic absorption peak.

In certain embodiments, the form a is further characterized by an infrared spectrum obtained by infrared spectroscopyAt 1593. + -. 2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1At least one of the wavenumbers of (a) shows a characteristic absorption peak.

In certain embodiments, the form a is an anhydrous form.

In certain embodiments, the form a is substantially pure.

In certain embodiments, the form a exhibits a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

In certain embodiments, the form a exhibits an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

In certain embodiments, the form a exhibits a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

In certain embodiments, the form a has an X-ray powder diffraction pattern substantially the same as figure 1.

In certain embodiments, the TGA profile of the crystalline form a is substantially the same as figure 2.

In certain embodiments, the DSC profile of form a is substantially the same as figure 3.

In certain embodiments, the form a has an infrared spectrum substantially the same as figure 4.

In another aspect, the present application provides a process for preparing form a of the compound of formula I as described above.

In certain embodiments, the method comprises: and (2) dropwise adding an anti-solvent into the normal solvent solution of the compound shown in the formula I, and stirring until a solid is precipitated to obtain the crystal form A, wherein the normal solvent comprises an ether solvent, a ketone solvent, an alcohol solvent, an ester solvent or a mixed solvent of the solvents, and the anti-solvent comprises an aliphatic hydrocarbon solvent, a nitrile solvent or a mixed solvent of the solvents.

In certain embodiments, wherein the positive solvent comprises Acetone (Acetone), THF (tetrahydrofuran), EtOH (ethanol), EtOAc (ethyl acetate), or a mixture of the foregoing solvents.

In certain embodiments, wherein the anti-solvent comprises IPAc (isopropyl acetate), ACN (acetonitrile), n-heptanes, or a mixture of the foregoing solvents.

In certain embodiments, the method comprises: dissolving a compound shown as a formula I in a solvent, filtering to obtain a filtrate, and cooling the filtrate until a solid is separated out to obtain the crystal form A, wherein the solvent comprises a ketone solvent, an ester solvent, an ether solvent or a mixed solvent of the solvents.

In certain embodiments, wherein the solvent comprises MIBK (methyl isobutyl ketone), IPAc (isopropyl acetate), or a mixed solvent of 2-MeTHF and MTBE.

In some embodiments, the volume ratio of 2-MeTHF to MTBE in the mixed solvent of 2-MeTHF and MTBE is about (1-3) to (3-1).

In certain embodiments, wherein the cooling filtrate comprises: the temperature of the filtrate is reduced from about 50-60 ℃ to about 0-10 ℃ at a rate of about 0.05-0.5 ℃/min.

In certain embodiments, the cooling filtrate further comprises: and if no solid is separated out after the filtrate is cooled, placing the filtrate at about-25 to-15 ℃ until solid is separated out, and then placing the filtrate at room temperature to volatilize the solvent to obtain the crystal form A.

In certain embodiments, the method comprises: and (2) placing a positive solvent solution of the compound shown in the formula I in an anti-solvent atmosphere to perform gas-liquid infiltration crystallization to obtain the crystal form A, wherein the positive solvent comprises an ether solvent, a ketone solvent, an ester solvent or a mixed solvent of the solvents, and the anti-solvent comprises an aliphatic hydrocarbon solvent, an aromatic hydrocarbon solvent, a nitrile solvent, an ether solvent or a mixed solvent of the solvents.

In certain embodiments, wherein the positive solvent comprises THF, EtOAc, 2-MeTHF, MEK (methyl ethyl ketone), or a mixture thereof.

In certain embodiments, wherein the anti-solvent comprises Toluene (Toluene), n-Heptane, CAN, MTBE, or a mixture thereof.

In certain embodiments, the method comprises: dissolving the compound shown in the formula I in a solvent, and volatilizing and drying at room temperature to obtain the crystal form A, wherein the solvent comprises an alcohol solvent.

In certain embodiments, wherein the solvent comprises EtOH.

In certain embodiments, the preparation of the compound of formula I comprises: reacting 1- (4- (4-amino-6- (methoxymethyl) pyrrolo [1,2-f ] [1,2,4] triazinyl) -2-fluorophenyl) -3- (2-fluoro-5- (trifluoromethyl) phenyl) urea (intermediate 1) with N-methylmorpholine-N-chloride in a solvent system comprising a heteroaromatic solvent to obtain the compound of formula I.

In certain embodiments, the preparation of the compound of formula I specifically comprises: 1- (4- (4-amino-6- (methoxymethyl) pyrrole [1,2-f ] [1,2,4] triazinyl) -2-fluorophenyl) -3- (2-fluoro-5- (trifluoromethyl) phenyl) urea was reacted with N-methylmorpholine-N-chloride in a solvent system, and a solid was precipitated at a pH of about 8 to 12 to obtain a compound represented by the formula I.

In certain embodiments, the preparation of the compound of formula I further comprises a purification step.

In certain embodiments, the purifying step comprises: and (3) carrying out at least one pulping, filtering and/or drying on the EOC317 compound obtained after suction filtration to obtain a purified EOC317 compound.

In certain embodiments, the solvent system comprises N-methylpyrrolidone, N-dimethylacetamide, or N, N-dimethylformamide.

In another aspect, the present application provides a pharmaceutical composition comprising the aforementioned crystalline form a of the compound represented by formula I and one or more pharmaceutically acceptable excipients.

In certain embodiments, the pharmaceutical composition further comprises one or more immunotherapeutic agents selected from the group consisting of: anti-CTLA 4 antibodies, anti-PD-1 antibodies, and anti-PD-L1 antibodies.

In another aspect, the present application provides the use of form a of the compound of formula I as described above or a pharmaceutical composition as described above for the preparation of a medicament for the treatment of cancer.

In another aspect, the present application provides a method comprising administering to a subject in need thereof a therapeutically effective amount of the aforementioned crystalline form a of the compound of formula I or the aforementioned pharmaceutical composition.

In certain embodiments, the subject has cancer.

In another aspect, the present application provides a medicament for treating cancer, the medicament comprising the aforementioned crystalline form a of the compound of formula I or the aforementioned pharmaceutical composition.

In another aspect, the present application provides a crystalline form M of a compound of formula I comprising about 0.2 to about 0.6 moles of water,

in an X-ray powder diffraction pattern expressed by a diffraction angle 2 theta angle obtained by using Cu-Kalpha radiation, the crystal form M has characteristic peaks at 2 theta angles of 8.1 +/-0.2 degrees, 12.0 +/-0.2 degrees and 13.5 +/-0.2 degrees.

In certain embodiments, the crystalline form M further has a characteristic peak at least one of 2 Θ angles selected from 10.4 ± 0.2 °, 11.5 ± 0.2 ° and 14.8 ± 0.2 ° in an X-ray powder diffraction pattern expressed in diffraction angle 2 Θ angles obtained using Cu-K α radiation.

In certain embodiments, the crystalline form M further has a characteristic peak at least one of 2 θ angles selected from 16.3 ± 0.2 ° and 23.9 ± 0.2 ° in an X-ray powder diffraction pattern expressed in terms of diffraction angle 2 θ angles obtained using Cu-K α radiation.

In certain embodiments, the crystalline form M contains about 0.3 moles of water per mole of crystalline form.

In certain embodiments, the crystalline form M is substantially pure.

In certain embodiments, the crystalline form M exhibits a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test.

In certain embodiments, the crystalline form M exhibits endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test.

In certain embodiments, the crystalline form M has an X-ray powder diffraction pattern substantially the same as figure 10.

In certain embodiments, the TGA/DSC profile of form M is substantially the same as figure 11.

In another aspect, the present application provides a process for preparing the aforementioned crystalline form M of the compound of formula I containing about 0.2 to 0.6 moles of water, comprising: dissolving a compound shown in a formula I in a solvent, filtering to obtain a filtrate, and cooling the filtrate until a solid is separated out to obtain the crystal form M, wherein the solvent comprises an alcohol solvent, aliphatic halogenated hydrocarbon or a mixed solvent of the above solvents.

In certain embodiments, the solvent comprises EtOH solvent or a mixed solvent of MeOH and DCM.

In some embodiments, the volume ratio of MeOH to DCM in the mixed solvent of MeOH and DCM is about (1-3): (3-1).

In certain embodiments, wherein the cooling filtrate further comprises: and if no solid is separated out after the filtrate is cooled, placing the filtrate at about-25 to-15 ℃ until solid is separated out, and then placing the filtrate at room temperature to volatilize the solvent to obtain the crystal form M.

In another aspect, the present application provides a pharmaceutical composition comprising the aforementioned crystalline form M of the compound of formula I containing about 0.2 to 0.6 moles of water and one or more pharmaceutically acceptable excipients.

In another aspect, the present application provides the use of the aforementioned crystalline form M of the compound of formula I containing about 0.2 to 0.6 moles of water and the aforementioned pharmaceutical composition for the preparation of a medicament for the treatment of cancer.

In another aspect, the present application provides a method comprising administering to a subject in need thereof a therapeutically effective amount of the aforementioned crystalline form M of the compound of formula I containing about 0.2-0.6 moles of water or the aforementioned pharmaceutical composition.

In certain embodiments, the subject has cancer.

In another aspect, the present application provides a medicament comprising the aforementioned crystalline form M of the compound of formula I containing about 0.2 to 0.6 moles of water or the aforementioned pharmaceutical composition for the treatment of cancer.

In another aspect, the present application provides a pharmaceutical composition comprising the aforementioned form a of the compound of formula I and/or form M of the compound of formula I containing about 0.2-0.6 moles of water, and one or more pharmaceutically acceptable excipients.

In another aspect, the present application provides the use of form a of the compound of formula I as described above, form M of the compound of formula I containing about 0.2 to 0.6 moles of water, or a pharmaceutical composition of the foregoing, in the preparation of a medicament for the treatment of cancer.

In another aspect, the present application provides a kit that may comprise two or more separate pharmaceutical compositions, at least one of which comprises the aforementioned crystalline form a of the compound of formula I and/or the aforementioned crystalline form M of the compound of formula I containing about 0.2 to 0.6 moles of water or the aforementioned pharmaceutical composition.

In another aspect, the present application provides a method of inhibiting FGFR and/or VEGFR2, comprising: administering to a subject in need thereof a therapeutically effective amount of the aforementioned crystalline form a of the compound of formula I, the aforementioned crystalline form M of the compound of formula I containing about 0.2-0.6 moles of water, and/or the aforementioned pharmaceutical composition.

Other aspects and advantages of the present application will be readily apparent to those skilled in the art from the following detailed description. Only exemplary embodiments of the present application have been shown and described in the following detailed description. As those skilled in the art will recognize, the disclosure of the present application enables those skilled in the art to make changes to the specific embodiments disclosed without departing from the spirit and scope of the invention as it is directed to the present application. Accordingly, the descriptions in the drawings and the specification of the present application are illustrative only and not limiting.

Drawings

The specific features of the invention to which this application relates are set forth in the appended claims. The features and advantages of the invention to which this application relates will be better understood by reference to the exemplary embodiments described in detail below and the accompanying drawings. The brief description of the drawings is as follows:

FIG. 1 shows an XRPD pattern for form A of the present application;

figure 2 shows a TGA profile of form a herein;

FIG. 3 shows a DSC curve of form A of the present application;

FIG. 4 shows an infrared spectrum of form A of the present application;

FIG. 5 is a DVS plot of form A of the present application;

FIG. 6 shows XRPD patterns of form A of the present application before and after DVS;

FIG. 7 shows XRPD patterns before and after micronization of form A of the present application;

FIG. 8 shows a PLM diagram of form A of the present application;

FIG. 9 shows a crystal modification A of the present application¹A HNMR map;

FIG. 10 shows an XRPD pattern of form M of the present application;

FIG. 11 shows a TGA/DSC curve of form M of the present application;

figure 12 shows a variable temperature XRPD pattern of form M of the present application;

FIG. 13 shows an XRPD pattern for form AF of the present application;

FIG. 14 shows a TGA/DSC curve of form AF of the present application;

FIG. 15 shows a crystalline form AF of the present application¹A HNMR map;

figure 16 shows an XRPD overlay of form a of the present application for pressure stability testing at different pressures;

figure 17 shows an XRPD overlay of form a of the present application with form AF in EtOH for a suspension competition assay;

figure 18 shows XRPD stacking of form a and form M of the present application in suspension competition experiments at different water activities;

FIG. 19 shows an XRPD overlay of form A, form AH and form AF of the present application;

FIG. 20 shows an XRPD pattern for form V of the present application;

FIG. 21 shows a TGA/DSC curve of form V of the present application;

FIG. 22 shows a crystal modification V of the present application¹A HNMR map;

figure 23 shows an XRPD pattern of form C of the present application;

FIG. 24 shows a TGA/DSC curve of form C of the present application;

FIG. 25 shows a crystal modification C of the present application¹A HNMR map;

figure 26 shows a temperature-variable XRPD pattern of form C of the present application.

Detailed Description

The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification.

Definition of terms

In this application, the term "N- {4- [ 4-amino-6- (methoxymethyl) -7- (morpholin-4-ylmethyl) pyrrolo [2,1-f ] [1,2,4] triazin-5-yl ] -2-fluorophenyl } -N' - [ 2-fluoro-5- (trifluoromethyl) phenyl ] urea", also commonly referred to as EOC317, having a chemical formula as shown in formula I and CAS number 939805-30-8, is an oral small Molecule Multimodal Kinase Inhibitor (MMKI). EOC317 induces apoptosis by blocking angiogenesis activation and downstream signaling based on inhibition of FGFR family and VEGFR2, thereby producing an anti-tumor effect.

As used herein, the terms "polymorph", "polymorph (polymorphs)", "crystal modification", "crystal form", "crystal modification", "polymorph form" and "crystal form" are understood to be synonymous and in this application refer to solid crystal forms of a compound or complex, including, but not limited to, single or multicomponent crystals, and/or polymorphs, solvates, hydrates, clathrates, co-crystals, salts, solvates of salts, hydrates of salts of compounds.

Polymorphs can be detected, identified, classified and characterized using techniques well known to those skilled in the art, such as, but not limited to: differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD), single crystal X-ray diffraction, vibrational spectroscopy, solution calorimetry, solid-state nuclear magnetic resonance (SSNMR), fourier transform-infrared spectroscopy (FT-IRspectrum), raman spectroscopy (Ramanspectrum), hot stage optical microscopy, Scanning Electron Microscopy (SEM), electron crystallography, and quantitative analysis, Particle Size Analysis (PSA), surface region analysis, solubility, and dissolution rate. Crystalline form (Polymorphism) can be characterized by the ability of a particular compound to crystallize in different crystalline modifications while maintaining the same chemical structure. Polymorphs of a given substance are chemically equivalent, containing the same atoms bonded to each other in the same manner, but differ in their crystal modifications, which may affect one or more physical properties such as dissolution rate, melting point, bulk density, stability, flow properties, and the like. The graphical representation of such data may undergo small changes (e.g., peak relative intensities and peak positions) due to factors such as instrument response changes and sample concentration and purity changes, as is well known to those skilled in the art. Nevertheless, one skilled in the art would be able to compare the graphical data in the figures of the present application with the graphical data generated for an unknown crystal form and confirm whether the two sets of graphical data characterize the same crystal form.

Unless otherwise indicated, when the present application refers to spectra or data presented in graphical form (e.g., XRPD, IR, raman, and NMR spectra), the term "peak" refers to a peak or other special feature caused by non-background noise that is recognizable to one of ordinary skill in the art.

As is well known in the field of X-ray powder diffraction (XRPD), for any given crystalline form, the equipment used, humidity, temperature, orientation of the powder crystals, and other parameters to obtain the X-ray powder diffraction pattern may cause some variability in the appearance, intensity, and position of the peaks in the diffraction pattern. See, for example, The United States Pharmacopeia #23, National Formulary #18, pages 1843-1844, 1995. In the present case, the variability of the ± 0.2 ° 2 θ peak positions takes into account these possible variations without hindering the unambiguous identification of the crystal form shown. The identification of the crystalline form can be based on any unique differential peak (in ° 2 θ units) or a combination thereof, typically the more prominent peak. Thus, in some embodiments, the crystalline compounds of the present application are characterized by XRPD patterns having certain peak positions, with substantially the same characteristics as the XRPD patterns provided in the figures of the present application. Depending on the instrument used in this application, the diffraction peak positions may have a tolerance of ± 0.2 °. For example, an X-ray powder diffraction pattern "substantially in accordance" with FIG. 1 provided herein may be the same as the XRPD pattern in the figures, or more likely it may be slightly different. Such XRPD patterns may not necessarily show every peak in the diffraction patterns presented herein, and/or may show slight variations in the appearance, intensity, or displacement of the peaks due to differences in the conditions involved in obtaining the data. One skilled in the art can determine whether a sample of a crystalline compound has the same crystalline form or a different crystalline form than the crystalline form disclosed herein by comparing their XRPD patterns. Similarly, one skilled in the art can determine whether a given diffraction peak position (expressed in ° 2 θ) from an XRPD pattern is at about the same position as the value presented herein. In the context of the present application, the 2 θ values in the X-ray powder diffraction pattern are all in degrees (°).

Also, as is well known in the field of Differential Scanning Calorimetry (DSC), the melting peak height of a DSC curve depends on many relevant factors such as sample preparation and test instrument conditions, while the peak position is relatively insensitive to experimental details. Thus, in some embodiments, the crystalline compounds of the present application are characterized by a DSC profile with characteristic peak positions having substantially the same properties as the DSC profile provided in the figures of the present application. Depending on the conditions of the instrument used in the test, there is a tolerance of + -3 deg.C, + -4 deg.C or + -5 deg.C for the melting temperature.

As is well known in the field of fourier transform-infrared spectroscopy (FT-IR), the position and shape of the absorption peak of infrared spectroscopy depends on the transition of the valence kinetic energy level in the sample molecule. Thus, in some embodiments, the crystalline compounds of the present application are characterized by a fourier transform-infrared spectrogram having characteristic peak positions and shapes, having substantially the same properties as the fourier transform-infrared spectrogram provided in the figures of the present application. According to the appendix IV C-infrared spectrophotometry of Chinese pharmacopoeia (2010 version) and the conditions of the instrument used in the test, the absorption peak is at 3000cm^-1Near the center, is +/-5 cm^-1Error margin of (2) at 1000cm^-1Nearby +/-2 cm^-1Error tolerance of (2).

An X-ray powder diffraction pattern, DSC profile, TGA profile, and fourier transform-infrared spectrum that are "substantially the same" or "substantially the same" generally means that at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90%, or at least about 95%, or at least about 99% of the peaks in the X-ray powder diffraction pattern, DSC profile, raman spectrum, and infrared spectrum are shown in the figures.

The term "substantially pure" generally refers to chemical purity and crystalline form purity, more specifically, a crystalline form is substantially free of one or more other crystalline forms, i.e., the crystalline form is at least about 60% pure, or at least about 70% pure, or at least about 80% pure, or at least about 85% pure, or at least about 90% pure, or at least about 93% pure, or at least about 95% pure, or at least about 98% pure, or at least about 99% pure, or at least about 99.5% pure, or at least about 99.6% pure, or at least about 99.7% pure, or at least about 99.8% pure, or at least about 99.9% pure, or contains other crystalline forms in the crystalline form, the percentage of which in the total volume or weight of the crystalline form is less than about 30% pure, or less than about 20% pure, or less than about 10% pure, or less than about 5% pure, or less than about 3% pure, or less than about 0.5%.

The purity of the crystal of the present application can be determined by, for example, a known method such as X-ray powder diffractometry, thermal analysis, or the like. The purity of the crystal or mixed crystal of the present application is not necessarily 100%, and may be not less than about 70%, or not less than about 80%, or not less than about 90%, or not less than about 95%, or not less than about 98%, and purity within this range may ensure quality.

The terms "about" and "approximately" as used herein generally mean within ± 10%, suitably within ± 5%, and especially within ± 1% of a given value or range. Alternatively, the terms "about" and "approximately" mean within an acceptable standard error of the mean, as would be apparent to one of ordinary skill in the art.

The term "solution" as used herein generally refers to a mixture containing at least one solvent and at least one compound that is at least partially soluble in the solvent.

The term "solvate" as used herein generally refers to having a solvent on the surface, in the crystal lattice, or both, such as, for example, water, acetic acid, acetone, acetonitrile, benzene, chloroform, carbon tetrachloride, methylene chloride, dimethyl sulfoxide, 1, 4-dioxane, ethanol, ethyl acetate, butanol, t-butanol, N-dimethylacetamide, N-dimethylformamide, formamide, formic acid, heptane, hexane, isopropanol, methanol, methyl ethyl ketone, l-methyl-2-pyrrolidone, nitromethane, polyethylene glycol, propanol, 2-acetone, pyridine, tetrahydrofuran, toluene, xylene, mixtures thereof, and the like. A specific example of a solvate is a hydrate, wherein the solvent on the surface, in the crystal lattice or on the surface and in the crystal lattice is water. The hydrates may or may not have other solvents than water on the surface of the substance, in the crystal lattice or both.

The term "positive solvent" as used herein generally refers to a solvent in which the EOC317 compound is well soluble, e.g., one or more of methanol, ethanol, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide; "antisolvent" generally refers to a solvent in which the EOC317 compound of the present application is poorly soluble, such as one or more of n-heptane, cyclopentyl methyl ether, tetrahydrofuran, diethyl ether, propylene glycol methyl ether, methyl tert-butyl ether, acetone, acetophenone, methyl isobutyl ketone, ethyl acetate, acetonitrile, methylene chloride.

The term "amorphous" generally refers to a solid form of molecules, atoms, and/or ions that is not crystalline. Amorphous solids do not exhibit a defined X-ray powder diffraction pattern.

Hygroscopicity is an important physical property of a raw material drug, and it directly affects storage stability, processability and process of manufacturing the drug. A dynamic water adsorption instrument (DVS) is adopted to examine the adsorption and desorption experiments of the sample on water at the temperature of 25 ℃ and at the relative humidity of 0-95% so as to determine the moisture-wicking performance of various crystal forms. The following table is the definition and range of hygroscopicity for the drug after equilibration at 25 ℃, 80% RH in chinese pharmacopoeia 2015 edition.

Deliquescence	Absorb sufficient water to form a liquid
		Has moisture absorption property	The moisture-drawing weight gain is not less than 15 percent
Has moisture absorption effect	The moisture-drawing weight gain is less than 15 percent but not less than 2 percent
		Slightly hygroscopic	The moisture-drawing weight gain is less than 2 percent but not less than 0.2 percent
No or almost no hygroscopicity	The moisture-attracting weight gain is less than 0.2 percent

The term "pharmaceutical composition" generally refers to a mixture of one or more compounds described herein, or a physiologically/pharmaceutically acceptable salt or prodrug thereof, with other chemical components, such as physiologically/pharmaceutically acceptable adjuvants, excipients, diluents, adjuvants, vehicles, and additional therapeutic agents. The purpose of the pharmaceutical composition is to facilitate the administration of the compound to an organism.

As described herein, the pharmaceutically acceptable compositions of the present application further comprise pharmaceutically acceptable excipients, such as, as used herein, any solvent, solid excipient, diluent, binder, disintegrant, or other liquid excipient, dispersing agent, flavoring or suspending agent, surfactant, isotonic agent, thickening agent, emulsifying agent, preservative, solid binder or lubricant, and the like, as appropriate for the particular target dosage form. As described in the following documents: in Remington, The Science and Practice of Pharmacy,21st edition,2005, ed.D.B.Troy, Lippincott Williams & Wilkins, Philadelphia, and Encyclopedia of Pharmaceutical Technology, eds.J.Swarbrick and J.C.Boylan, 1988. Annu 1999, Marcel Dekker, New York, taken together with The disclosure of this document, indicates that different adjuvants can be used In The preparation of pharmaceutically acceptable compositions and their well-known methods of preparation. Except insofar as any conventional adjuvant is incompatible with the compounds of the present application, e.g., any adverse biological effect produced or interaction in a deleterious manner with any other component of a pharmaceutically acceptable composition, their use is contemplated herein.

Substances that may serve as pharmaceutically acceptable excipients include, but are not limited to, ion exchangers; aluminum; aluminum stearate; lecithin; serum proteins, such as human serum albumin; buffer substances, such as phosphates; glycine; sorbic acid; potassium sorbate; partial glyceride mixtures of saturated vegetable fatty acids; water; salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts; colloidal silica; magnesium trisilicate; polyvinylpyrrolidone; polyacrylate esters; a wax; polyethylene-polyoxypropylene-blocking polymers; lanolin; sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; gum powder; malt; gelatin; talc powder; adjuvants such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic salt; ringer's solution; ethanol; phosphoric acid buffer solution; and other non-toxic suitable lubricants such as sodium lauryl sulfate and magnesium stearate; a colorant; a release agent; coating the coating material; a sweetener; a flavoring agent; a fragrance; preservatives and antioxidants.

The pharmaceutical compositions of the present application may be administered orally, by injection, topically, buccally, or via an implantable kit. The term "administration by injection" as used herein includes subcutaneous, intravenous, intramuscular, intraarticular, intrasynovial (intracavitary), intrasternal, intramembranous, intraocular, intrahepatic, intralesional, and intracranial injection or infusion techniques. For example, the pharmaceutical compositions of the present application may be administered orally in any acceptable oral dosage form, including, but not limited to, capsules, tablets, aqueous suspensions or solutions. As another example, the pharmaceutical compositions of the present application may be administered by sterile injection in the form of aqueous or oleaginous suspensions, which may be formulated according to the known art using suitable dispersing, wetting and suspending agents.

The term "cancer" means a group of diseases involving abnormal cell growth, with the potential to invade or spread to other parts of the body. Cancers are classified according to the type of cells that are similar to tumor cells and therefore presumed to be of tumor origin. These types include carcinomas, sarcomas, lymphomas and leukemias, germ cell tumors and blastomas. The term "cancer" is used to denote a cancer derived from epithelial cells. This group includes many of the most common cancers, and includes almost all those that develop in the breast, prostate, lung, pancreas and colon.

For example, the term "cancer" includes, but is not limited to, solid tumors, hematological cancers (e.g., leukemia, lymphoma, myeloma (e.g., multiple myeloma)), and metastatic lesions. In one embodiment, the cancer is a solid tumor. Examples of solid tumors include malignancies, such as sarcomas and carcinomas, e.g., adenocarcinomas of various organ systems, such as those affecting the lung, breast, ovary, lymph, gastrointestinal (e.g., colon), anal, genital, and genitourinary tracts (e.g., kidney, urothelium, bladder cells, prostate), pharynx, CNS (e.g., brain cells, nerve cells, or glial cells), head and neck, skin (e.g., melanoma), and pancreas, and adenocarcinomas including malignancies, such as colon, rectal, renal cell, liver, non-small cell lung, small intestine, and esophageal cancers. The cancer may be in an early stage, a mid stage, an advanced stage, or may be a metastatic cancer.

In one non-limiting example, the cancer is selected from lung cancer (e.g., non-small cell lung cancer (NSCLC) (e.g., NSCLC with squamous and/or non-squamous histology, or NSCLC adenocarcinoma)), melanoma (e.g., advanced melanoma), renal cancer (e.g., renal cell carcinoma), liver cancer, myeloma (e.g., multiple myeloma), prostate cancer, breast cancer (e.g., breast cancer that does not express one, both, or all of the estrogen receptor, progesterone receptor, or Her2/neu, e.g., triple negative breast cancer), colorectal cancer, pancreatic cancer, head and neck cancer (e.g., Head and Neck Squamous Cell Carcinoma (HNSCC)), anal cancer, gastroesophageal cancer, thyroid cancer, cervical cancer, lymphoproliferative disease (e.g., post-transplant lymphoproliferative disease), or hematological cancer, T-cell lymphoma, B-cell lymphoma, Non-hodgkin's lymphoma or leukemia (e.g., myeloid leukemia or lymphoid leukemia).

The term "administration" refers to the contact of an exogenous drug, therapeutic agent, diagnostic agent, or composition with an animal, human, subject, cell, tissue, organ, or biological fluid when applied to the animal, human, experimental subject, cell, tissue, organ, or biological fluid. "administration" may refer to therapeutic, pharmacokinetic, diagnostic, research and experimental methods. Administration of the cells includes contacting the agent with the cells, and contacting the agent with a fluid, wherein the fluid is in contact with the cells. "administering" also means treating, e.g., a cell in vitro and ex vivo, by a reagent, a diagnostic, a binding composition, or by another cell. When applied to human, veterinary or research subjects, "administration" refers to therapeutic treatment, prophylactic or preventative measures, research and diagnostic applications.

The term "therapeutically effective amount" of a compound of the invention refers to an amount of a compound of the present application that will elicit the biological or medical response of a subject (e.g., a reduction or inhibition of enzyme or protein activity, or amelioration of symptoms, alleviation of a disorder, or slowing or delaying the progression of a disease, etc.). In one non-limiting embodiment, the term "therapeutically effective amount" refers to an amount of a compound of the invention that, when administered to a subject, is effective to (1) at least partially ameliorate, inhibit, and/or ameliorate a condition, or disorder or disease (i) mediated by FGFR1, or (ii) associated with the activity of FGFR1, or (iii) characterized by FGFR1 activity (normal or abnormal); or (2) reducing or inhibiting the activity of FGFR 1. In another non-limiting embodiment, the term "therapeutically effective amount" refers to an amount of a compound that is effective to at least partially reduce or inhibit the activity of FGFR1 when administered to a cell, or a tissue, or a non-cellular biological material or medium; or at least partially reducing or inhibiting expression of FGFR 1.

As used herein, the term "treating" or "treatment" of any disease or condition, in some embodiments refers to ameliorating the disease or condition (i.e., slowing or arresting or reducing the development of the disease or at least one clinical symptom thereof). In other embodiments, "treating" or "treatment" refers to moderating and/or improving at least one physical parameter, including physical parameters that may not be perceived by the patient. In other embodiments, "treating" or "treatment" refers to modulating the disease or disorder, either physiologically (e.g., stabilizing a parameter of the body), or both, from the body (e.g., stabilizing a perceptible symptom). In other embodiments, "treating" or "treatment" refers to preventing or delaying the onset, occurrence, or worsening of a disease or disorder.

The term "subject" refers to an animal. In certain embodiments, the animal is a mammal. For example, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, fish, birds, and the like. In one non-limiting example, the subject is a human.

The term "programmed death 1" or "PD-1" includes isoforms, species homologs of mammals such as human PD-1, and analogs comprising at least one common epitope with PD-1. The amino acid sequence of PD-1 (e.g., human PD-1) is known in the art, e.g., Shinohara T et al (1994) Genomics [ Genomics ]23(3): 704-6; finger LR et al Gene (1997)197(1-2): 177-87.

The term "programmed death ligand 1" or "PD-L1" includes isoforms, species homologs of mammals such as human PDL1, human PD-1, and analogs comprising at least one common epitope with PD-L1. The amino acid sequence of PD-L1 (e.g., human PD-1) is known in the art, e.g., Dong et al (1999) Nat Med [ Nature medicine ]5(12): 1365-9; freeman et al (2000) J Exp Med [ journal of Experimental medicine ]192(7): 1027-34).

The term "combination" refers to a fixed combination, or combined administration, in dosage unit form, wherein the crystalline form of the compound of formula I and the combination partner (i.e. immunotherapeutic agent) may be administered separately at the same time or separately within time intervals, particularly where these time intervals allow the combination partners to show a synergistic, e.g. synergistic effect. The individual components may be packaged in a kit or separately. One or both components (e.g., powder or liquid) may be reconstituted or diluted to a desired dosage prior to administration.

The term "pharmaceutical combination" refers to a fixed combination in one dosage unit form or a non-fixed combination or kit for combined administration, wherein two or more therapeutic agents may be administered independently at the same time or separately within time intervals, in particular where these time intervals allow the combination partners to show a synergistic, e.g. synergistic effect. The term "fixed combination" means that the crystalline form of the compound having formula I and the combination partner (i.e., immunotherapeutic agent) are administered to the patient simultaneously, in the form of a single entity or dose. The term "non-fixed combination" means a crystalline form of a compound having formula I and a combination partner (i.e., an immunotherapeutic agent) that are administered to a patient as separate entities simultaneously, concurrently or sequentially (without specific time constraints), wherein such administration provides therapeutically effective levels of both compounds in the body of the patient. The latter is also applicable to cocktail therapies, such as the administration of three or more therapeutic agents. In one non-limiting example, the pharmaceutical combination is a non-fixed combination.

The terms "co-administration" or "combined administration" and the like are intended to encompass administration of selected combination partners (i.e., immunotherapeutic agents) to a single subject (e.g., patient) in need thereof, and are intended to include treatment regimens in which the agents are not necessarily administered by the same route of administration or simultaneously.

Detailed Description

the form a may show characteristic peaks at 2 theta angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 ° in an X-ray powder diffraction pattern expressed by a diffraction angle 2 theta angle obtained using Cu-K alpha radiation.

In certain embodiments, the form a may further exhibit a characteristic peak at least one of 2 θ angles selected from 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 ° in an X-ray powder diffraction pattern expressed in terms of diffraction angle 2 θ angles obtained using Cu-K α radiation.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 13.3 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 13.7 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 22.0 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 ° and 13.7 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 ° and 22.0 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., and 22.0 + -0.2 deg..

In certain embodiments, the form a may further exhibit a characteristic peak at least one of 2 θ angles selected from 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 ° in an X-ray powder diffraction pattern expressed in terms of diffraction angle 2 θ angles obtained using Cu-K α radiation.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 11.3 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 19.1 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 19.8 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form A shows characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 11.3 + -0.2 deg., and 19.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 11.3 ± 0.2 ° and 19.8 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., and 19.8 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., and 11.3 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., and 19.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., and 19.8 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., and 19.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., and 19.8 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 19.1 + -0.2 deg., and 19.8 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., and 19.8 + -0.2 deg..

In certain embodiments, the form a may further exhibit a characteristic peak at least one of 2 θ angles selected from 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 ° in an X-ray powder diffraction pattern expressed in terms of diffraction angle 2 θ angles obtained using Cu-K α radiation.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 20.8 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 21.2 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 24.1 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 20.8 ± 0.2 ° and 21.2 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 20.8 ± 0.2 ° and 24.1 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., and 20.8 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., and 21.2 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., and 24.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 20.8 + -0.2 deg., and 21.2 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 20.8 + -0.2 deg., and 24.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., and 20.8 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., and 21.2 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., and 24.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., and 21.2 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., and 24.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg..

In certain embodiments, the form a may further exhibit a characteristic peak at least one of 2 θ angles selected from 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 °, and 27.4 ± 0.2 ° in an X-ray powder diffraction pattern obtained using Cu-K α radiation and expressed in terms of diffraction angle 2 θ angles.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 22.9 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 25.1 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 26.4 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 ° and 27.4 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 22.9 ± 0.2 ° and 25.1 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 22.9 ± 0.2 ° and 26.4 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 22.9 ± 0.2 ° and 27.4 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 25.1 ± 0.2 ° and 26.4 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 25.1 ± 0.2 ° and 27.4 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 22.9 + -0.2 deg., 25.1 + -0.2 deg., and 26.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 22.9 + -0.2 deg., 25.1 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 22.9 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 25.1 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 22.9 + -0.2 deg., 25.1 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., and 22.9 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., and 25.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., and 26.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 22.9 + -0.2 deg., and 25.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 22.9 + -0.2 deg., and 26.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 22.9 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 25.1 + -0.2 deg., and 26.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 25.1 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 22.9 + -0.2 deg., 25.1 + -0.2 deg., and 26.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta angles, the form A shows characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 22.9 + -0.2 deg., 25.1 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 22.9 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 25.1 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 22.9 + -0.2 deg., 25.1 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., and 22.9 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., and 25.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., and 26.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 22.9 + -0.2 deg., and 25.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 22.9 + -0.2 deg., and 26.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 22.9 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 25.1 + -0.2 deg., and 26.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 25.1 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 22.9 + -0.2 deg., 25.1 + -0.2 deg., and 26.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 22.9 + -0.2 deg., 25.1 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 22.9 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 25.1 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 22.9 + -0.2 deg., 25.1 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., 24.1 + -0.2 deg., and 22.9 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., 24.1 + -0.2 deg., and 25.1 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., 24.1 + -0.2 deg., and 26.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., 24.1 + -0.2 deg., and 27.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 θ, the form A may show characteristic peaks at 2 θ angles of 8.3. + -. 0.2 °, 9.6. + -. 0.2 °, 18.1. + -. 0.2 °, 13.3. + -. 0.2 °, 13.7. + -. 0.2 °, 22.0. + -. 0.2 °, 11.3. + -. 0.2 °, 19.1. + -. 0.2 °, 19.8. + -. 0.2 °, 20.8. + -. 0.2 °, 21.2. + -. 0.2 °, 24.1. + -. 0.2 °, 22.9. + -. 0.2 ° and 25.1. + -. 0.2 °.

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 θ, the form A may show characteristic peaks at 2 θ angles of 8.3. + -. 0.2 °, 9.6. + -. 0.2 °, 18.1. + -. 0.2 °, 13.3. + -. 0.2 °, 13.7. + -. 0.2 °, 22.0. + -. 0.2 °, 11.3. + -. 0.2 °, 19.1. + -. 0.2 °, 19.8. + -. 0.2 °, 20.8. + -. 0.2 °, 21.2. + -. 0.2 °, 24.1. + -. 0.2 °, 22.9. + -. 0.2 ° and 26.4. + -. 0.2 °.

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 θ, the form A may show characteristic peaks at 2 θ angles of 8.3. + -. 0.2 °, 9.6. + -. 0.2 °, 18.1. + -. 0.2 °, 13.3. + -. 0.2 °, 13.7. + -. 0.2 °, 22.0. + -. 0.2 °, 11.3. + -. 0.2 °, 19.1. + -. 0.2 °, 19.8. + -. 0.2 °, 20.8. + -. 0.2 °, 21.2. + -. 0.2 °, 24.1. + -. 0.2 °, 22.9. + -. 0.2 ° and 27.4. + -. 0.2 °.

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 θ, the form A may show characteristic peaks at 2 θ angles of 8.3. + -. 0.2 °, 9.6. + -. 0.2 °, 18.1. + -. 0.2 °, 13.3. + -. 0.2 °, 13.7. + -. 0.2 °, 22.0. + -. 0.2 °, 11.3. + -. 0.2 °, 19.1. + -. 0.2 °, 19.8. + -. 0.2 °, 20.8. + -. 0.2 °, 21.2. + -. 0.2 °, 24.1. + -. 0.2 °, 25.1. + -. 0.2 ° and 26.4. + -. 0.2 °.

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 θ, the form A may show characteristic peaks at 2 θ angles of 8.3. + -. 0.2 °, 9.6. + -. 0.2 °, 18.1. + -. 0.2 °, 13.3. + -. 0.2 °, 13.7. + -. 0.2 °, 22.0. + -. 0.2 °, 11.3. + -. 0.2 °, 19.1. + -. 0.2 °, 19.8. + -. 0.2 °, 20.8. + -. 0.2 °, 21.2. + -. 0.2 °, 24.1. + -. 0.2 °, 25.1. + -. 0.2 ° and 27.4. + -. 0.2 °.

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 θ, the form A may show characteristic peaks at 2 θ angles of 8.3. + -. 0.2 °, 9.6. + -. 0.2 °, 18.1. + -. 0.2 °, 13.3. + -. 0.2 °, 13.7. + -. 0.2 °, 22.0. + -. 0.2 °, 11.3. + -. 0.2 °, 19.1. + -. 0.2 °, 19.8. + -. 0.2 °, 20.8. + -. 0.2 °, 21.2. + -. 0.2 °, 24.1. + -. 0.2 °, 26.4. + -. 0.2 ° and 27.4. + -. 0.2 °.

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 θ, the form A may show characteristic peaks at 2 θ angles of 8.3. + -. 0.2 °, 9.6. + -. 0.2 °, 18.1. + -. 0.2 °, 13.3. + -. 0.2 °, 13.7. + -. 0.2 °, 22.0. + -. 0.2 °, 11.3. + -. 0.2 °, 19.1. + -. 0.2 °, 19.8. + -. 0.2 °, 20.8. + -. 0.2 °, 21.2. + -. 0.2 °, 24.1. + -. 0.2 °, 22.9. + -. 0.2 °, 25.1. + -. 0.2 ° and 26.4. + -. 0.2 °.

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 θ, the form A may show characteristic peaks at 2 θ angles of 8.3. + -. 0.2 °, 9.6. + -. 0.2 °, 18.1. + -. 0.2 °, 13.3. + -. 0.2 °, 13.7. + -. 0.2 °, 22.0. + -. 0.2 °, 11.3. + -. 0.2 °, 19.1. + -. 0.2 °, 19.8. + -. 0.2 °, 20.8. + -. 0.2 °, 21.2. + -. 0.2 °, 24.1. + -. 0.2 °, 22.9. + -. 0.2 °, 25.1. + -. 0.2 ° and 27.4. + -. 0.2 °.

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 θ, the form A may show characteristic peaks at 2 θ angles of 8.3. + -. 0.2 °, 9.6. + -. 0.2 °, 18.1. + -. 0.2 °, 13.3. + -. 0.2 °, 13.7. + -. 0.2 °, 22.0. + -. 0.2 °, 11.3. + -. 0.2 °, 19.1. + -. 0.2 °, 19.8. + -. 0.2 °, 20.8. + -. 0.2 °, 21.2. + -. 0.2 °, 24.1. + -. 0.2 °, 22.9. + -. 0.2 °, 26.4. + -. 0.2 ° and 27.4. + -. 0.2 °.

For example, in an X-ray powder diffraction pattern using Cu-Ka radiation expressed in terms of diffraction angle 2 θ, the form A may show characteristic peaks at 2 θ angles of 8.3. + -. 0.2 °, 9.6. + -. 0.2 °, 18.1. + -. 0.2 °, 13.3. + -. 0.2 °, 13.7. + -. 0.2 °, 22.0. + -. 0.2 °, 11.3. + -. 0.2 °, 19.1. + -. 0.2 °, 19.8. + -. 0.2 °, 20.8. + -. 0.2 °, 21.2. + -. 0.2 °, 24.1. + -. 0.2 °, 25.1. + -. 0.2 °, 26.4. + -. 0.2 ° and 27.4. + -. 0.2 °.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., 24.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 22.9 + -0.2 deg., 25.1 + -0.2 deg., 26.4 + -0.2 deg., and 27.4 + -0.2 deg.

In certain embodiments, the form a can be at 3476 ± 2cm in an infrared spectrogram obtained by infrared spectroscopic characterization^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in makingIn an X-ray powder diffraction pattern which is obtained by Cu-Kalpha radiation and expressed by a diffraction angle 2 theta angle, the crystal form A can show characteristic peaks at 2 theta angles of 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees, 18.1 +/-0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees, 22.0 +/-0.2 degrees, 11.3 +/-0.2 degrees, 19.1 +/-0.2 degrees, 19.8 +/-0.2 degrees, 20.8 +/-0.2 degrees, 21.2 +/-0.2 degrees and 24.1 +/-0.2 degrees; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 °, 9.6 + -0.2 °, 18.1 + -0.2 °, 13.3 + -0.2 °, 13.7 + -0.2 °, 22.0 + -0.2 °, 11.3 + -0.2 °, 19.1 + -0.2 °, 19.8 + -0.2 °, 20.8 + -0.2 °, 21.2 + -0.2 °, 24.1 + -0.2 °, 22.9 + -0.2 °, 25.1 + -0.2 °, 26.4 + -0.2 ° and 27.4 + -0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

In certain embodiments, the form a may also be at a value selected from 2871 ± 2cm in an ir spectrum obtained using ir spectroscopy characterization^-1，2806±2cm^-1And 3104 + -2 cm^-1At least one of the wavenumbers of (a) shows a characteristic absorption peak.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1And 2871 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1And 2806. + -. 2cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in the case of IR spectroscopyIn the figure, the form A can be in 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1And 2806. + -. 2cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in X-rays obtained using Cu-Ka radiation and expressed in diffraction angle 2 thetaIn a powder diffraction pattern, the crystal form A can show characteristic peaks at 2 theta angles of 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees, 18.1 +/-0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees and 22.0 +/-0.2 degrees; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg.; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may be 2 DEG of 8.3 + -0.2 DEG, 9.6 + -0.2 DEG, 18.1 + -0.2 DEG, 13.3 + -0.2 DEG, 13.7 + -0.2 DEG, 22.0 + -0.2 DEG, 11.3 + -0.2 DEG, 19.1 + -0.2 DEG, 19.8 + -0.2 DEG, 20.8 + -0.2 DEG, 21.2 + -0.2 DEG, 24.1 + -0.2 DEG, 22.9 + -0.2 DEG, 25.1 + -0.2 DEG, 26.4 + -0.2 DEG and 27.4 + -0.2 DEGA characteristic peak is displayed at an angle theta; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

In certain embodiments, the form a may also be selected from 1593 ± 2cm in an ir spectrum obtained by ir spectroscopy characterization^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1At least one of the wavenumbers of (a) shows a characteristic absorption peak.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-11593. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1And 1537. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1And 1316. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1And 1123. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1And 849 +/-2 cm^-1Shows characteristic absorption peaks at wave numbers of。

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，1593±2cm^-1And 1537. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，1593±2cm^-1，1537±2cm^-1And 1316. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1And 1123. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1And 849 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-11593. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1And 1537. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1And 1316. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1And 1123. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1And 849 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1And 1537. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1And 1316. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1And 1123. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1And 849 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg.; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 °, 9.6 + -0.2 °, 18.1 + -0.2 °, 13.3 + -0.2 °, 13.7 + -0.2 °, 22.0 + -0.2 °, 11.3 + -0.2 °, 19.1 + -0.2 °, 19.8 + -0.2 °, 20.8 + -0.2 °, 21.2 + -0.2 °, 24.1 + -0.2 °, 22.9 + -0.2 °, 25.1 + -0.2 °, 26.4 + -0.2 ° and 27.4 + -0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

In certain embodiments, the form a may be an anhydrous form.

For example, the form A can be an anhydrous form and irradiated using Cu-KaIn an X-ray powder diffraction pattern expressed by diffraction angle 2 theta obtained by injection, the crystal form A can show characteristic peaks at 2 theta angles of 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees, 18.1 +/-0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees, 22.0 +/-0.2 degrees, 11.3 +/-0.2 degrees, 19.1 +/-0.2 degrees, 19.8 +/-0.2 degrees, 20.8 +/-0.2 degrees, 21.2 +/-0.2 degrees, 24.1 +/-0.2 degrees, 22.9 +/-0.2 degrees, 25.1 +/-0.2 degrees, 26.4 +/-0.2 degrees and 27.4 +/-0.2 degrees; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

In certain embodiments, the form a can be substantially pure.

For example, the purity of form a may be at least about 60%, or at least about 70%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 91%, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99%, or at least about 99.1%, or at least about 99.2%, or at least about 99.3%, or at least about 99.4%, or at least about 99.5%, or at least about 99.6%, or at least about 99.7%, or at least about 99.8%, or at least about 99.9%.

In certain embodiments, the form a may exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg.; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 °, 9.6 + -0.2 °, 18.1 + -0.2 °, 13.3 + -0.2 °, 13.7 + -0.2 °, 22.0 + -0.2 °, 11.3 + -0.2 °, 19.1 + -0.2 °, 19.8 + -0.2 °, 20.8 + -0.2 °, 21.2 + -0.2 °, 24.1 + -0.2 °, 22.9 + -0.2 °, 25.1 + -0.2 °, 26.4 + -0.2 ° and 27.4 + -0.2 °; the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a can exhibit, in a thermogravimetric analysis test, heating to about 200 ℃ in the presence of a catalystThe weight loss was about 0.8%.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

As another example, in the X-ray powder diffraction pattern expressed by the diffraction angle 2 theta angle obtained by using Cu-Kalpha radiation, the crystal form A can be 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees, 18.1 +/-Characteristic peaks are shown at 2 theta angles of 0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees, 22.0 +/-0.2 degrees, 11.3 +/-0.2 degrees, 19.1 +/-0.2 degrees, 19.8 +/-0.2 degrees, 20.8 +/-0.2 degrees, 21.2 +/-0.2 degrees, 24.1 +/-0.2 degrees, 22.9 +/-0.2 degrees, 25.1 +/-0.2 degrees, 26.4 +/-0.2 degrees and 27.4 +/-0.2 degrees; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

As another example, in an X-ray powder diffraction pattern obtained by using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A can be 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees, 18.1 +/-0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees, 22.0 +/-0.2 degrees, 11.3 +/-0.2 degrees, 19.1 +/-0.2 degrees and 19.8 +/-0.2 degreesCharacteristic peaks are shown at 2 theta; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

In certain embodiments, the form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg.; the form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 °, 9.6 + -0.2 °, 18.1 + -0.2 °, 13.3 + -0.2 °, 13.7 + -0.2 °, 22.0 + -0.2 °, 11.3 + -0.2 °, 19.1 + -0.2 °, 19.8 + -0.2 °, 20.8 + -0.2 °, 21.2 + -0.2 °, 24.1 + -0.2 °, 22.9 + -0.2 °, 25.1 + -0.2 °, 26.4 + -0.2 ° and 27.4 + -0.2 °; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

Also, for example, in using Cu-Ka radiationTo an X-ray powder diffraction pattern expressed by diffraction angle 2 theta angles, wherein the crystal form A can show characteristic peaks at 2 theta angles of 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees and 18.1 +/-0.2 degrees; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a exhibits a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

As another example, in an X-ray powder diffraction pattern obtained by using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the crystal form A can be in a range of 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees, 18.1 +/-0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees, 22.0 +/-0.2 degrees, 11.3 +/-0.2 degrees,characteristic peaks are shown at 2 theta angles of 19.1 +/-0.2 degrees, 19.8 +/-0.2 degrees, 20.8 +/-0.2 degrees, 21.2 +/-0.2 degrees and 24.1 +/-0.2 degrees; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

Also, for example, in diffraction obtained using Cu-Ka radiationIn an X-ray powder diffraction pattern represented by an angle 2 theta angle, the crystal form A can show characteristic peaks at 2 theta angles of 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees, 18.1 +/-0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees and 22.0 +/-0.2 degrees; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of;and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

In certain embodiments, the form a can exhibit a weight change of less than about 0.11% in the relative humidity range from 0% RH to 80% RH at 25 ℃ in a dynamic moisture sorption test.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg.; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 °, 9.6 + -0.2 °, 18.1 + -0.2 °, 13.3 + -0.2 °, 13.7 + -0.2 °, 22.0 + -0.2 °, 11.3 + -0.2 °, 19.1 + -0.2 °, 19.8 + -0.2 °, 20.8 + -0.2 °, 21.2 + -0.2 °, 24.1 + -0.2 °, 22.9 + -0.2 °, 25.1 + -0.2 °, 26.4 + -0.2 ° and 27.4 + -0.2 °; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A is 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can be shown to be relatively at 25 ℃ in a dynamic moisture adsorption testThe humidity varied by less than about 0.11% by weight from 0% RH to 80% RH humidity.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a exhibits a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

As another example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic features at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg., respectivelyA peak; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a can be shown in a thermogravimetric analysis test upon heating to about 2Weight loss of about 0.8% at 00 ℃; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and said form a exhibits a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test.

In certain embodiments, the form a can have an X-ray powder diffraction pattern substantially the same as figure 1.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A shows characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg.; and the X-ray powder diffraction pattern of form a is substantially the same as figure 1.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 °, 9.6 + -0.2 °, 18.1 + -0.2 °, 13.3 + -0.2 °, 13.7 + -0.2 °, 22.0 + -0.2 °, 11.3 + -0.2 °, 19.1 + -0.2 °, 19.8 + -0.2 °, 20.8 + -0.2 °, 21.2 + -0.2 °, 24.1 + -0.2 °, 22.9 + -0.2 °, 25.1 + -0.2 °, 26.4 + -0.2 ° and 27.4 + -0.2 °; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

As another example, the diffraction angle 2 theta obtained by using Cu-Ka radiationThe form a can show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 ° in an X-ray powder diffraction pattern of (a); and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form A can be heated under hot conditionsAn analytical test showed a weight loss of about 0.8% when heated to about 200 ℃; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A is 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form A may be differentialA scanning calorimetry test showed an endothermic peak at about 205 ℃; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and saidThe X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a is substantially the same as figure 1.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of the crystal form A can be shown1 are substantially identical.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

In certain embodiments, the TGA profile of the crystalline form a may be substantially the same as figure 2.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and the TGA profile of said form a may be substantially the same as figure 2.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and the TGA profile of said form a may be substantially the same as figure 2.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and the TGA profile of said form a may be substantially the same as figure 2.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg.; and the TGA profile of said form a may be substantially the same as figure 2.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 °, 9.6 + -0.2 °, 18.1 + -0.2 °, 13.3 + -0.2 °, 13.7 + -0.2 °, 22.0 + -0.2 °, 11.3 + -0.2 °, 19.1 + -0.2 °, 19.8 + -0.2 °, 20.8 + -0.2 °, 21.2 + -0.2 °, 24.1 + -0.2 °, 22.9 + -0.2 °, 25.1 + -0.2 °, 26.4 + -0.2 ° and 27.4 + -0.2 °; and the TGA profile of said form a may be substantially the same as figure 2.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of said form a may be substantially the same as figure 2.

As another example, in an X-ray powder diffraction pattern obtained by using Cu-Kalpha radiation and expressed by a diffraction angle 2 theta angle, the form A can be 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees, 18.1 +/-0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees and 22.0 +/-0.2 degreesShows a characteristic peak at the 2 theta angle of (a); and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of said form a may be substantially the same as figure 2.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ from a relative humidity in the range of 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the TGA profile of said form a may be substantially the same as figure 2.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of said form a may be substantially the same as figure 2.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of said form a may be substantially the same as figure 2.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of said form a may be substantially the same as figure 2.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of said form a may be substantially the same as figure 2.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of said form a may be substantially the same as figure 2.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of said form a may be substantially the same as figure 2.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and use an infrared spectrometerIn the obtained infrared spectrogram, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of said form a may be substantially the same as figure 2.

In certain embodiments, the DSC profile of form a may be substantially the same as figure 3.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and the DSC profile of said form a may be substantially the same as figure 3.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and the DSC profile of said form a may be substantially the same as figure 3.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and the DSC profile of said form a may be substantially the same as figure 3.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg.; and the DSC profile of said form a may be substantially the same as figure 3.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 °, 9.6 + -0.2 °, 18.1 + -0.2 °, 13.3 + -0.2 °, 13.7 + -0.2 °, 22.0 + -0.2 °, 11.3 + -0.2 °, 19.1 + -0.2 °, 19.8 + -0.2 °, 20.8 + -0.2 °, 21.2 + -0.2 °, 24.1 + -0.2 °, 22.9 + -0.2 °, 25.1 + -0.2 °, 26.4 + -0.2 ° and 27.4 + -0.2 °; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and a standSaid form a exhibiting an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a exhibits a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form A shows in the thermogravimetric analysis test in the presence ofA weight loss of about 0.8% when heated to about 200 ℃; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form A may beShows a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

As another example, in an X-ray powder diffraction pattern obtained by using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A can be 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees, 18.1 +/-0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees, 22.0 +/-0.2 degrees, 11.3 +/-0.2 degrees, 19.1 +/-0.2 degrees, 19.8 +/-0.2 degrees, 20.8 +/-0.2 degrees, 21 degreesCharacteristic peaks are shown at 2 theta angles of 2 +/-0.2 degrees, 24.1 +/-0.2 degrees, 22.9 +/-0.2 degrees, 25.1 +/-0.2 degrees, 26.4 +/-0.2 degrees and 27.4 +/-0.2 degrees; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

In certain embodiments, the infrared spectrum of form a may be substantially the same as figure 4.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and the infrared spectrum of form a may be substantially the same as figure 4.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and the infrared spectrum of form a may be substantially the same as figure 4.

For example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and the infrared spectrum of form a may be substantially the same as figure 4.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 deg., 9.6 + -0.2 deg., 18.1 + -0.2 deg., 13.3 + -0.2 deg., 13.7 + -0.2 deg., 22.0 + -0.2 deg., 11.3 + -0.2 deg., 19.1 + -0.2 deg., 19.8 + -0.2 deg., 20.8 + -0.2 deg., 21.2 + -0.2 deg., and 24.1 + -0.2 deg.; and the infrared spectrum of form a may be substantially the same as figure 4.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form A may show characteristic peaks at 2 theta angles of 8.3 + -0.2 °, 9.6 + -0.2 °, 18.1 + -0.2 °, 13.3 + -0.2 °, 13.7 + -0.2 °, 22.0 + -0.2 °, 11.3 + -0.2 °, 19.1 + -0.2 °, 19.8 + -0.2 °, 20.8 + -0.2 °, 21.2 + -0.2 °, 24.1 + -0.2 °, 22.9 + -0.2 °, 25.1 + -0.2 °, 26.4 + -0.2 ° and 27.4 + -0.2 °; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a exhibits a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a is substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

As another example, in an X-ray powder diffraction pattern obtained by using Cu-Ka radiation and expressed by a diffraction angle 2 theta angle, the form A can be 8.3 +/-0.2 degrees and 9 degreesCharacteristic peaks are shown at 2 theta angles of 6 +/-0.2 degrees, 18.1 +/-0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees and 22.0 +/-0.2 degrees; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

As another example, in an X-ray powder diffraction pattern expressed by a diffraction angle 2 theta angle obtained using Cu-Ka radiationThe crystal form A can show characteristic peaks at 2 theta angles of 8.3 +/-0.2 degrees, 9.6 +/-0.2 degrees, 18.1 +/-0.2 degrees, 13.3 +/-0.2 degrees, 13.7 +/-0.2 degrees, 22.0 +/-0.2 degrees, 11.3 +/-0.2 degrees, 19.1 +/-0.2 degrees, 19.8 +/-0.2 degrees, 20.8 +/-0.2 degrees, 21.2 +/-0.2 degrees and 24.1 +/-0.2 degrees; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of said form A may be substantially as shown in figure 2The same as above; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 ° and 18.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 ° and 22.0 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the crystal form A can show that the relative humidity is from 0% RH to 80% at 25 ℃ in a dynamic moisture adsorption testA weight change in the RH humidity range of less than about 0.11%; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 ° and 19.8 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ angle, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 ° and 24.1 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form a may show characteristic peaks at 2 θ angles of 8.3 ± 0.2 °, 9.6 ± 0.2 °, 18.1 ± 0.2 °, 13.3 ± 0.2 °, 13.7 ± 0.2 °, 22.0 ± 0.2 °, 11.3 ± 0.2 °, 19.1 ± 0.2 °, 19.8 ± 0.2 °, 20.8 ± 0.2 °, 21.2 ± 0.2 °, 24.1 ± 0.2 °, 22.9 ± 0.2 °, 25.1 ± 0.2 °, 26.4 ± 0.2 ° and 27.4 ± 0.2 °; and in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; and the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

in an infrared spectrogram obtained by using infrared spectrum characterization, the crystal form A can be in 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1And 849 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of (c).

In certain embodiments, the form a may be an anhydrous form.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a may be an anhydrous form.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a may be an anhydrous form.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a may be an anhydrous form.

In certain embodiments, the form a can be substantially pure.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization,the crystal form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change of less than about 0.11% at 25 ℃ in the relative humidity range from 0% RH to 80% RH in a dynamic moisture sorption test.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of the crystal form AMay be substantially the same as in fig. 1.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the TGA profile of said form a may be substantially the same as figure 2.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the TGA profile of said form a may be substantially the same as figure 2.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A is 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the TGA profile of said form a may be substantially the same as figure 2.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; TGA of said form AThe map may be substantially the same as in fig. 2.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; the TGA profile of form a can be substantially the same as figure 2.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; the TGA profile of form a can be substantially the same as figure 2.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the DSC profile of said form a may be substantially the same as figure 3.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the DSC profile of said form a may be substantially the same as figure 3.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the infrared spectrum of form a may be substantially the same as figure 4.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the infrared spectrum of form a may be substantially the same as figure 4.

For example, in an infrared spectrogram obtained by using infrared spectrum characterization, the form A can be 3476 +/-2 cm^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1And 1719. + -.2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1And 3104 + -2 cm^-1Wave ofSeveral show characteristic absorption peaks; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

For another example, the form a can be at 3476 ± 2cm in an ir spectrogram obtained by ir spectroscopy^-1，3371±2cm^-1，3292±2cm^-1，1719±2cm^-1，2871±2cm^-1，2806±2cm^-1，3104±2cm^-1，1593±2cm^-1，1537±2cm^-1，1316±2cm^-1，1123±2cm^-1，849±2cm^-1And 680 +/-2 cm^-1Shows a characteristic absorption peak at the wavenumber of; and the form a can exhibit a weight loss of about 0.8% upon heating to about 200 ℃ in a thermogravimetric analysis test; and said form a can exhibit an endothermic peak at about 205 ℃ in a differential scanning calorimetry test; and the form a can exhibit a weight change at 25 ℃ in the relative humidity range from 0% RH to 80% RH of less than about 0.11% in a dynamic moisture sorption test; and the X-ray powder diffraction pattern of form a may be substantially the same as figure 1; the TGA profile of form a can be substantially the same as figure 2; and the DSC profile of said form a may be substantially the same as figure 3; and the infrared spectrum of form a may be substantially the same as figure 4.

In some embodiments, the method may comprise: and (2) dropwise adding an anti-solvent into the normal solvent solution of the compound shown in the formula I, and stirring until a solid is precipitated to obtain the crystal form A, wherein the normal solvent can comprise ethers, ketones, alcohols, ester solvents or a mixed solvent of the solvents, and the anti-solvent can comprise aliphatic hydrocarbons, nitrile solvents or a mixed solvent of the solvents.

In certain embodiments, wherein the positive solvent may comprise Acetone (Acetone), THF (tetrahydrofuran), EtOH (ethanol), EtOAc (ethyl acetate), or a mixture of the foregoing solvents.

In certain embodiments, wherein the anti-solvent may comprise IPAc (isopropyl acetate), ACN (acetonitrile), n-heptanes (n-heptane), or a mixture of the foregoing solvents.

In some embodiments, the method may comprise: dissolving a compound shown in a formula I in a solvent, filtering to obtain a filtrate, and cooling the filtrate until a solid is separated out to obtain the crystal form A, wherein the solvent can comprise a ketone solvent, an ester solvent, an ether solvent or a mixed solvent of the solvents.

In certain embodiments, wherein the solvent may comprise MIBK (methyl isobutyl ketone), IPAc (isopropyl acetate), or a mixed solvent of 2-MeTHF and MTBE.

For example, the volume ratio of 2-MeTHF to MTBE in the mixed solvent of 2-MeTHF and MTBE may be about (1-3): 3-1.

As another example, the volume ratio of 2-MeTHF to MTBE in the mixed solvent of 2-MeTHF and MTBE may be about 1: 1.

In certain embodiments, the cooling filtrate comprises: the temperature of the filtrate can be reduced from about 50-60 ℃ to about 0-10 ℃ at a cooling rate of about 0.05-0.5 ℃/min.

For example, the cooling filtrate comprises: the temperature of the filtrate can be reduced from about 50-60 ℃ to about 0-5 ℃ at a cooling rate of about 0.05-0.2 ℃/min.

As another example, the cooling filtrate includes: the filtrate may be cooled from about 50 ℃ to about 5 ℃ at a cooling rate of about 0.1 ℃/min.

In certain embodiments, the cooling filtrate may further comprise: and if no solid is separated out after the filtrate is cooled, placing the filtrate at about-25 to-15 ℃ until solid is separated out, and then placing the filtrate at room temperature to volatilize the solvent to obtain the crystal form A.

In some embodiments, the method may comprise: and (2) placing a positive solvent solution of the compound shown in the formula I in an anti-solvent atmosphere to perform gas-liquid infiltration crystallization to obtain the crystal form A, wherein the positive solvent can comprise ethers, ketones and ester solvents or a mixed solvent of the solvents, and the anti-solvent can comprise aliphatic hydrocarbons, aromatic hydrocarbons, nitriles, ether solvents or a mixed solvent of the solvents.

In certain embodiments, wherein the positive solvent may comprise THF, EtOAc, 2-MeTHF, MEK (methyl ethyl ketone), or a mixture thereof.

In certain embodiments, wherein the anti-solvent may comprise Toluene (Toluene), n-Heptane, CAN, MTBE, or a mixture thereof.

In some embodiments, the method may comprise: dissolving the compound shown in the formula I in a solvent, and volatilizing and drying at room temperature to obtain the crystal form A, wherein the solvent comprises an alcohol solvent.

In certain embodiments, wherein the solvent may comprise EtOH.

In certain embodiments, the preparation of the compound of formula I may comprise: reacting 1- (4- (4-amino-6- (methoxymethyl) pyrrolo [1,2-f ] [1,2,4] triazinyl) -2-fluorophenyl) -3- (2-fluoro-5- (trifluoromethyl) phenyl) urea (intermediate 1) with N-methylmorpholine-N-chloride in a solvent system, which may include a heteroaromatic solvent, to provide the compound of formula I.

In some embodiments, the preparation of the compound of formula I may specifically include: 1- (4- (4-amino-6- (methoxymethyl) pyrrole [1,2-f ] [1,2,4] triazinyl) -2-fluorophenyl) -3- (2-fluoro-5- (trifluoromethyl) phenyl) urea was reacted with N-methylmorpholine-N-chloride in a solvent system, and a solid was precipitated at a pH of about 9 to 10 to obtain a compound represented by the formula I.

In certain embodiments, the preparation of the compound of formula I may further comprise a purification step.

In certain embodiments, the purifying step may comprise: and (3) carrying out at least one pulping, filtering and/or drying on the EOC317 compound obtained after suction filtration to obtain a purified EOC317 compound.

In certain embodiments, the solvent system may include N-methylpyrrolidone, N-dimethylacetamide, or N, N-dimethylformamide.

In another aspect, the present application provides a pharmaceutical composition comprising the aforementioned crystalline form a of the compound represented by formula I and one or more pharmaceutically acceptable excipients. Suitable excipients are disclosed. Other adjuvants known in the art may be used without departing from the purpose and scope of the present application.

In some embodiments, the pharmaceutical composition can be formulated for a particular route of administration, such as oral, parenteral, and rectal administration, and the like. In addition, the pharmaceutical compositions may be prepared in solid form (including but not limited to capsules, tablets, pills, granules, powders, or suppositories), or in liquid form (including but not limited to solutions, suspensions, or emulsions). The pharmaceutical compositions may be subjected to conventional pharmaceutical procedures (e.g., sterilization) and/or may contain conventional inert diluents, lubricants, carriers or buffers, and adjuvants (e.g., solvents, preservatives, stabilizers, wetting agents, emulsifiers, bulking agents, and the like).

Tablets may contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets. These excipients may be, for example, inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch or alginic acid; binders, for example, starch, gelatin or acacia; and lubricating agents, such as magnesium stearate, stearic acid or talc. These tablets are either uncoated or coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a long-lasting effect. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed. Formulations for oral use may be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin or olive oil.

In certain embodiments, the compound or composition is prepared for oral administration, such as, for example, tablets or capsules, and optionally packaged in a multi-dose form suitable for storing and/or dispensing unit doses of the pharmaceutical product. Examples of suitable packaging include, but are not limited to, hermetically sealed foils, unit dose containers (e.g., vials), blister packs, and strip packs.

In another aspect, the present application provides a kit that may comprise two or more separate pharmaceutical compositions, at least one of which contains form a of the compound of formula I as described previously. In one embodiment, the kit may comprise a device (e.g., a container, a separate bottle, or a separate foil packet) for separately retaining the compositions. An example of such a kit is a blister pack, such as is typically used for tablets, capsules and the like.

In certain embodiments, the kit can be used for administering different dosage forms (e.g., oral and parenteral), for administering separate compositions at different dosage intervals, or for titrating separate compositions against one another.

In another aspect, the present application provides the use of form a of the compound of formula I as described above or a pharmaceutical composition as described above for the preparation of a medicament useful for the treatment of cancer.

In another aspect, the present application provides a method, which may comprise administering to a subject in need thereof a therapeutically effective amount of the aforementioned crystalline form a of the compound of formula I or the aforementioned pharmaceutical composition.

In certain embodiments, the method may further comprise co-administering to a subject in need thereof one or more immunotherapeutic agents selected from the group consisting of: anti-CTLA 4 antibodies, anti-PD-1 antibodies, and anti-PD-L1 antibodies.

In certain embodiments, the subject may have cancer.

In the present application, the cancer may be lung cancer, non-small cell lung (NSCL) cancer, bronchoalveolar cell lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, cancer of the stomach, colon cancer, breast cancer, uterine cancer, fallopian tube, endometrial cancer, cervical cancer, vaginal cancer, vulva cancer, hodgkin's disease, esophageal cancer, small intestine cancer, cancer of the endocrine system, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urinary tract cancer, penile cancer, prostate cancer, bladder cancer, cancer of the kidney or ureter, renal cell cancer, renal pelvis cancer, mesothelioma, hepatocellular carcinoma, bile duct cancer, Central Nervous System (CNS) neoplasms, spinal axis tumors, brain stem glioma, glioblastoma multiforme, astrocytoma, schwannoma, ependymoma, medulloblastoma, meningioma, squamous cell carcinoma, pituitary adenoma, lymphoma, lymphocytic leukemia, including refractory forms of any of the foregoing cancers, or a combination of one or more of the foregoing cancers. In one embodiment, such cancer is a solid tumor selected from breast cancer, lung cancer, colon cancer, ovarian cancer, melanoma cancer, bladder cancer, cancer of the kidney, kidney cancer, liver cancer, head and neck cancer, colorectal cancer, pancreatic cancer, cancer of the stomach, esophageal cancer, mesothelioma or prostate cancer. In another embodiment, such cancer is a hematological tumor, such as, for example, leukemia (such as AML, CLL), lymphoma, myeloma. In yet another embodiment, the cancer is breast cancer, lung cancer, colon cancer, colorectal cancer, pancreatic cancer, gastric cancer or prostate cancer.

In another aspect, the present application provides a method of inhibiting FGFR and/or VEGFR2, which method can comprise: administering to a subject in need thereof a therapeutically effective amount of the aforementioned crystalline form a of the compound of formula I or the aforementioned pharmaceutical composition.

in an X-ray powder diffraction pattern expressed by a diffraction angle 2 theta angle obtained by using Cu-Kalpha radiation, the crystal form M can have characteristic peaks at 2 theta angles of 8.1 +/-0.2 degrees, 12.0 +/-0.2 degrees and 13.5 +/-0.2 degrees.

In certain embodiments, the crystalline form M may further have a characteristic peak at least one of 2 θ angles selected from 10.4 ± 0.2 °, 11.5 ± 0.2 ° and 14.8 ± 0.2 ° in an X-ray powder diffraction pattern expressed in terms of diffraction angle 2 θ angles obtained using Cu-K α radiation.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., and 10.4 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., and 11.5 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., and 14.8 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., and 11.5 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., and 14.8 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 11.5 + -0.2 deg., and 14.8 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., and 14.8 + -0.2 deg..

In certain embodiments, the crystalline form M may further have a characteristic peak at least one of 2 θ angles selected from 16.3 ± 0.2 ° and 23.9 ± 0.2 ° in an X-ray powder diffraction pattern expressed in terms of diffraction angle 2 θ angles obtained using Cu-K α radiation.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., and 16.3 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., and 23.9 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed in terms of diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 16.3 + -0.2 deg., and 23.9 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., 14.8 + -0.2 deg., and 16.3 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., 14.8 + -0.2 deg., and 23.9 + -0.2 deg..

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., 14.8 + -0.2 deg., 16.3 + -0.2 deg., and 23.9 + -0.2 deg..

In certain embodiments, the crystalline form M may contain about 0.3 moles of water per mole of crystalline form.

For example, in an X-ray powder diffraction pattern using Cu — K α radiation expressed in terms of diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 ° and 13.5 ± 0.2 °; and said crystalline form M may contain about 0.3 moles of water per mole of crystalline form.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., and 14.8 + -0.2 deg.; and said crystalline form M may contain about 0.3 moles of water per mole of crystalline form.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., 14.8 + -0.2 deg., 16.3 + -0.2 deg., and 23.9 + -0.2 deg.; and said crystalline form M may contain about 0.3 moles of water per mole of crystalline form.

In certain embodiments, the crystalline form M may be substantially pure.

For example, the purity of form M may be at least about 60%, or at least about 70%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 91%, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99%, or at least about 99.1%, or at least about 99.2%, or at least about 99.3%, or at least about 99.4%, or at least about 99.5%, or at least about 99.6%, or at least about 99.7%, or at least about 99.8%, or at least about 99.9%.

In certain embodiments, the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test.

For example, in an X-ray powder diffraction pattern using Cu — K α radiation expressed in terms of diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 ° and 13.5 ± 0.2 °; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., and 14.8 + -0.2 deg.; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., 14.8 + -0.2 deg., 16.3 + -0.2 deg., and 23.9 + -0.2 deg.; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test.

In certain embodiments, the crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test.

For example, in an X-ray powder diffraction pattern using Cu — K α radiation expressed in terms of diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 ° and 13.5 ± 0.2 °; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., and 14.8 + -0.2 deg.; and said crystalline form M exhibits endothermic peaks at about 119.8 ℃ and 135.6 ℃ in differential scanning calorimetry.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., 14.8 + -0.2 deg., 16.3 + -0.2 deg., and 23.9 + -0.2 deg.; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the crystalline form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 ° and 13.5 ± 0.2 °; and said crystalline form M exhibits a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 °, 13.5 ± 0.2 °, 10.4 ± 0.2 °, 11.5 ± 0.2 ° and 14.8 ± 0.2 °; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 °, 13.5 ± 0.2 °, 10.4 ± 0.2 °, 11.5 ± 0.2 °, 14.8 ± 0.2 °, 16.3 ± 0.2 ° and 23.9 ± 0.2 °; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test.

In certain embodiments, the form M can have an X-ray powder diffraction pattern substantially the same as figure 10.

For example, in an X-ray powder diffraction pattern using Cu — K α radiation expressed in terms of diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 ° and 13.5 ± 0.2 °; and the X-ray powder diffraction pattern of form M can be substantially the same as figure 10.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., and 14.8 + -0.2 deg.; and the X-ray powder diffraction pattern of form M can be substantially the same as figure 10.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., 14.8 + -0.2 deg., 16.3 + -0.2 deg., and 23.9 + -0.2 deg.; and the X-ray powder diffraction pattern of form M can be substantially the same as figure 10.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the crystalline form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 ° and 13.5 ± 0.2 °; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test; and the X-ray powder diffraction pattern of form M can be substantially the same as figure 10.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 °, 13.5 ± 0.2 °, 10.4 ± 0.2 °, 11.5 ± 0.2 ° and 14.8 ± 0.2 °; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test; and the X-ray powder diffraction pattern of form M can be substantially the same as figure 10.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 °, 13.5 ± 0.2 °, 10.4 ± 0.2 °, 11.5 ± 0.2 °, 14.8 ± 0.2 °, 16.3 ± 0.2 ° and 23.9 ± 0.2 °; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test; and the X-ray powder diffraction pattern of form M can be substantially the same as figure 10.

In certain embodiments, the TGA/DSC profile of form M can be substantially the same as figure 11.

For example, in an X-ray powder diffraction pattern using Cu — K α radiation expressed in terms of diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 ° and 13.5 ± 0.2 °; and the TGA/DSC profile of said crystalline form M may be substantially the same as figure 11.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., and 14.8 + -0.2 deg.; and the TGA/DSC profile of said crystalline form M may be substantially the same as figure 11.

For example, in an X-ray powder diffraction pattern obtained using Cu-Ka radiation and expressed by diffraction angle 2 theta, the form M may have characteristic peaks at 2 theta angles of 8.1 + -0.2 deg., 12.0 + -0.2 deg., 13.5 + -0.2 deg., 10.4 + -0.2 deg., 11.5 + -0.2 deg., 14.8 + -0.2 deg., 16.3 + -0.2 deg., and 23.9 + -0.2 deg.; and the TGA/DSC profile of said crystalline form M may be substantially the same as figure 11.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed in terms of diffraction angle 2 θ, the crystalline form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 ° and 13.5 ± 0.2 °; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test; and the X-ray powder diffraction pattern of said crystalline form M may be substantially the same as figure 10; and the TGA/DSC profile of said crystalline form M may be substantially the same as figure 11.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 °, 13.5 ± 0.2 °, 10.4 ± 0.2 °, 11.5 ± 0.2 ° and 14.8 ± 0.2 °; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test; and the X-ray powder diffraction pattern of said crystalline form M may be substantially the same as figure 10; and the TGA/DSC profile of said crystalline form M may be substantially the same as figure 11.

For another example, in an X-ray powder diffraction pattern obtained using Cu — K α radiation and expressed by a diffraction angle 2 θ, the form M may have characteristic peaks at 2 θ angles of 8.1 ± 0.2 °, 12.0 ± 0.2 °, 13.5 ± 0.2 °, 10.4 ± 0.2 °, 11.5 ± 0.2 °, 14.8 ± 0.2 °, 16.3 ± 0.2 ° and 23.9 ± 0.2 °; and the crystalline form M may exhibit a weight loss of about 4.4% upon heating to about 100 ℃ in a thermogravimetric analysis test; and said crystalline form M can exhibit endothermic peaks at about 119.8 ℃ and 135.6 ℃ in a differential scanning calorimetry test; and the X-ray powder diffraction pattern of said crystalline form M may be substantially the same as figure 10; and the TGA/DSC profile of said crystalline form M may be substantially the same as figure 11.

In another aspect, the present application provides a method for preparing form M of the compound of formula I as described above, containing about 0.2 to 0.6 moles of water, which may comprise: dissolving the compound shown in the formula I in a solvent, filtering to obtain a filtrate, and cooling the filtrate until a solid is separated out to obtain the crystal form M, wherein the solvent can comprise an alcohol solvent, aliphatic halogenated hydrocarbon or a mixed solvent of the solvents.

In certain embodiments, the solvent may comprise EtOH solvent or a mixed solvent of MeOH and DCM.

For example, the volume ratio of MeOH to DCM in the mixed solvent of MeOH and DCM can be about (1-3): (3-1).

For another example, the volume ratio of MeOH to DCM in the MeOH and DCM mixed solvent may be about 3: 1.

In certain embodiments, wherein the cooling filtrate may comprise: the temperature of the filtrate is reduced from about 50-60 ℃ to about 0-10 ℃ at a rate of about 0.05-0.5 ℃/min.

For example, wherein the cooling filtrate may comprise: the temperature of the filtrate is reduced from about 50-60 ℃ to about 0-5 ℃ at a rate of about 0.05-0.2 ℃/min.

For another example, wherein the cooling filtrate may comprise: the filtrate is cooled from about 50 ℃ to a temperature in the range of about 5 ℃ at a cooling rate of about 0.1 ℃/min.

In certain embodiments, wherein the cooling filtrate may further comprise: and if no solid is separated out after the filtrate is cooled, placing the filtrate at about-25 to-15 ℃ until solid is separated out, and then placing the filtrate at room temperature to volatilize the solvent to obtain the crystal form M.

In another aspect, the present application provides a pharmaceutical composition that may comprise the aforementioned crystalline form M of the compound of formula I containing about 0.2 to 0.6 moles of water and one or more pharmaceutically acceptable excipients.

In another aspect, the present application provides a kit that may comprise two or more separate pharmaceutical compositions, at least one of which contains the aforementioned crystalline form M of the compound of formula I. In one embodiment, the kit comprises a device (e.g., a container, a separate bottle, or a separate foil packet) for separately retaining the compositions. An example of such a kit is a blister pack, such as is typically used for tablets, capsules and the like.

In another aspect, the present application provides the use of the aforementioned crystalline form M of the compound of formula I containing about 0.2 to 0.6 moles of water and the aforementioned pharmaceutical composition for the preparation of a medicament useful for the treatment of cancer.

In another aspect, the present application provides a method that may comprise administering to a subject in need thereof a therapeutically effective amount of the aforementioned crystalline form M of the compound of formula I containing about 0.2-0.6 moles of water or the aforementioned pharmaceutical composition.

In certain embodiments, the subject may have cancer.

In another aspect, the present application provides a method of inhibiting FGFR and/or VEGFR2, which method can comprise: administering to a subject in need thereof a therapeutically effective amount of the aforementioned crystalline form M of the compound of formula I or the aforementioned pharmaceutical composition.

Without wishing to be bound by any theory, the following examples are only intended to illustrate the crystal forms, preparation methods, uses and the like of the present application, and are not intended to limit the scope of the invention of the present application.

Examples

The invention will be further illustrated by the following specific examples, which are not intended to limit the scope of the invention. The skilled person can make modifications to the preparation method and the apparatus used within the scope of the claims, and such modifications should also be considered as the scope of protection of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

The abbreviations used in the present invention are explained as follows:

XRPD: powder X-ray diffraction

IR: infrared spectroscopy

DSC: differential scanning calorimetry

TGA: thermogravimetric analysis

DVS: dynamic moisture adsorption

HPLC: high performance liquid chromatography

RH: relative humidity

Apparatus and method

X-ray powder diffraction (XRPD)

XRPD patterns are in PANALYTIC EMPyrean and X' Pert³The scanning parameters are shown in table 1.

TABLE 1 XRPD test parameters

Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC)

TGA and DSC graphs were collected on a TA Q5000/Discovery 5500 thermogravimetric analyzer and a TA Q2000/Discovery 2500 differential scanning calorimeter, respectively, and the test parameters are shown in Table 2.

TABLE 2 TGA and DSC test parameters

If not otherwise specified in the examples, the room temperature is 20 ℃ to 30 ℃.

Dynamic water adsorption (DVS)

Dynamic water adsorption (DVS) curves were collected on a DVS Intrasic in SMS (surface Measurement systems). The relative humidity at 25 ℃ was corrected for the deliquescence point of LiCl, Mg (NO3)2 and KCl, and the test parameters are shown in Table 3.

TABLE 3 DVS test parameters

Infrared spectrum (IR)

Samples for IR spectrometry were prepared using a potassium bromide tabletting method and tested using a transmission FTIR spectrometer. The spectrometer is PERKIN-ELMER Spectrum 65 or the like

Liquid nuclear magnetic resonance of hydrogen spectrum (¹H Solution NMR)

Collecting hydrogen spectrum liquid-state nuclear magnetic spectrum on Bruker 400M nuclear magnetic resonance apparatus, DMSO-d₆As a solvent.

Polarizing microscope (PLM)

PLM pictures were taken using an Axio Scope A1 microscope from Carl Zeiss German.

The starting materials used in the following examples can be prepared according to the prior art, for example according to the method described in CN109928976A, but are not limiting conditions for the preparation of the crystalline forms of the present invention.

EXAMPLE 1 preparation of EOC317 Compounds

1.1 reaction

Under the protection of nitrogen, sequentially adding 1- (4- (4-amino-6- (methoxymethyl) pyrrole [1,2-f ] [1,2,4] triazinyl) -2-fluorophenyl) -3- (2-fluoro-5- (trifluoromethyl) phenyl) urea, N-methylmorpholine-N-chloride and N, N-dimethylformamide into a 50L jacketed reaction kettle 1, heating to 50-90 ℃, and stirring the reaction solution for 6-8 h to obtain an EOC317 solution;

1.2 quenching

Adding dilute hydrochloric acid (3.66%) into the reaction solution, stirring the reaction solution at 50-90 ℃ for 1-2 h, and cooling the solution to room temperature; adjusting the solution to pH 9-10 with sodium hydroxide, stirring the solution for 1-2 h, filtering the mixed solution, and washing a filter cake with water;

1.3 beating + filtration + drying

Sequentially adding the wet filter cake, acetone and dichloromethane tetrahydrofuran into a reaction kettle, stirring the solution for 10-50 h at 20-25 ℃, filtering the mixed solution, and washing the filter cake with acetone; and (3) drying the mixture for 16-18 h at the temperature of below 50 ℃ in vacuum to obtain an EOC317 amorphous compound.

Example 2: preparation of form A

2.1 dissolution

Adding 8.37kg of ethyl acetate, 7.44kg of absolute ethyl alcohol and 0.186kg of purified water into a reaction kettle, stirring for 10-20 min, adding the pure product of the EOC317 compound obtained in the example 1, raising the temperature in the reaction kettle to 55-65 ℃, stirring for 0.5-1 h, and filtering;

2.2 crystallization

Raising the temperature in the kettle to 55-65 ℃, dropwise adding 26.04kg of n-heptane at the temperature of 55-65 ℃, stirring for 2-3 h after dropwise adding, cooling to 20-30 ℃, stirring for 10-11 h, and filtering;

2.3 drying

And (3) drying the filter cake for 10-12 h in vacuum at the temperature of below 50 ℃ to obtain the crystal form A.

The X-ray powder diffraction data of the crystal form A is shown in the table 4 through XRPD detection, and the diffraction pattern is shown in figure 1.

TABLE 4X-ray powder diffraction data for form A

The TGA of form a is shown in figure 2 and has a mass loss of about 0.8% when heated to 200 ℃.

DSC of form a as shown in figure 3, only one endothermic peak was observed at 205.0 ℃ (onset temperature).

FIG. 4 shows the IR spectrum of form A at 3476cm^-1，3371cm^-1And 3290cm^-1The stretching vibration of the nitrogen-hydrogen bond indicates that the structure contains an N-H structure; 3104cm^-1The position is unsaturated hydrocarbon stretching vibration, and the structure contains ═ C-H; 1719cm^-1Stretching vibration absorption of carbonyl, which indicates that the structure contains a C ═ O structure; 1593cm^-1And 1537cm^-1For the vibration of the skeleton of the benzene ring, 849 and 680cm^-1The out-of-plane bending vibration of the aromatic hydrogen surface shows that the structure contains a benzene ring structure; 1316cm^-1And 1123cm^-1C-N and C-O telescopic vibration absorption signals are used, and the C-N and C-O structures are shown in the structure; the infrared spectral characteristics of this sample are consistent with the chemical structure of the EOC317 compound.

To investigate the hygroscopicity of form a and the solid state stability under different humidity conditions, a dynamic moisture sorption (DVS) test was performed. Figure 5 shows a DVS plot for form a showing that the sample had an increase in relative humidity from 0% RH to 80% RH of 0.11% at 25 ℃, indicating that form a is almost non-hygroscopic.

X-ray powder diffraction patterns of form a before and after DVS testing are shown in fig. 6, showing that form a did not change before and after DVS testing.

Figure 7 shows the X-ray powder diffraction patterns before and after micronization of form a, showing that the form before and after micronization has not changed.

FIG. 8 shows a PLM of form A showing that form A is small irregular particles with partial agglomeration.

Of form A¹H NMR is shown in FIG. 9, which shows no significant solvent is found in the sampleAnd (4) remaining. The crystal form A has no obvious weight loss before 200 ℃, and the DSC has only one endothermic signal and no obvious solvent residue, which indicates that the crystal form A is an anhydrous crystal form.

Example 3: preparation of form A

3.1 anti-solvent addition

Weighing about 20mg of each pure EOC317 compound, dissolving the pure EOC317 compound in 0.2-1.0 mL of an ortho-solvent, adding the corresponding anti-solvent into the clear solution, stirring while dropwise adding until solid is separated out, and stopping dropwise adding if no solid is separated out after about 10mL of the anti-solvent is added. Solids were separated by centrifugation and tested for XRPD.

Table 5 anti-solvent addition preparation of form a

3.2 Slow Cooling

About 20mg of each pure EOC317 compound was weighed into a 3-mL vial, 1mL of the corresponding solvent was added, the mixture was stirred at 50 ℃ for about 2 hours and then filtered (PTFE filter with a pore size of 0.45 μm) to obtain a filtrate, and the obtained filtrate was placed in a biochemical incubator and cooled from 50 ℃ to 5 ℃ at a cooling rate of 0.1 ℃/min, and the sample was kept at 5 ℃ before testing XRPD. If the solution is still clear, it is transferred to-20 ℃ and then evaporated at room temperature. XRPD testing of the resulting solid

Table 6 preparation of crystal form a by slow cooling

*: the clear solution was transferred to-20 ℃ and then evaporated at room temperature.

3.3 gas-liquid permeation

Weighing about 20mg of each pure EOC317 compound, dissolving the pure EOC317 compound in 0.1-0.4 mL of corresponding normal solvent to obtain a saturated solution, placing the saturated solution in a 3-mL vial, filtering if the saturated solution is not dissolved, taking another 20-mL vial, adding about 4mL of anti-solvent into the other 20-mL vial, placing the 3-mL vial filled with the filtrate in the 20-mL vial in an open manner, sealing the 20-mL vial, and standing at room temperature. When solid evolution was observed, the solid was collected and tested for XRPD.

Table 7 gas-liquid infiltration preparation of form a

3.4 Slow volatilization

20mg of the EOC317 compound was weighed into 3-mL vials, and 1.0mL of the corresponding solvent was added, and the mixture was filtered (PTFE filter with a pore size of 0.45 μm) to obtain a filtrate. The vial containing the clear solution was sealed with a sealing film and punctured with four small holes on it, left to stand and slowly evaporate at room temperature. When a solid precipitated, the resulting solid was collected and tested for XRPD.

Table 8 slow volatilization preparation of form a

Example 4: grinding test of Crystal form A

About 20mg of form a (820613-01-a) was weighed into a mortar, added with the corresponding solvent, and manually milled for about 5 minutes for XRPD, with the results shown in table 9, and remained as form a after milling.

TABLE 9 abrasive form A

Example 5: humidity induction test of crystal form A

4 temperature induction experiments were set up using different solvents, approximately 20mg of form a (820613-01-a) was weighed into a 3mL vial, a saturated salt solution with a relative humidity of 40% -90% was prepared, 4mL of the saturated salt solution was placed into a 20mL vial, the 3mL vial was opened into the 20mL vial, and the 20mL vial was sealed. XRPD measurements were performed after 7 days at room temperature, the results are shown in table 10, and form a remained after humidity induction.

Table 10 humidity induced form a

Example 6: preparation of crystalline form M

About 20mg of each pure EOC317 compound was weighed into a 3-mL vial, 1mL of the corresponding solvent was added, the mixture was stirred at 50 ℃ for about 2 hours and then filtered (PTFE filter with a pore size of 0.45 μm) to obtain a filtrate, and the obtained filtrate was placed in a biochemical incubator and cooled from 50 ℃ to 5 ℃ at a cooling rate of 0.1 ℃/min, and the sample was kept at 5 ℃ before testing XRPD. If the solution is still clear, it is transferred to-20 ℃ and then evaporated at room temperature. The resulting solid was subjected to XRPD testing.

TABLE 11 preparation of crystalline form M by slow cooling

The XRPD overlay of the different batches of samples is shown in fig. 10, with X-ray powder diffraction data as shown in table 12.

TABLE 12X-ray powder diffraction data for form M

Two batches of crystalline form M samples 820613-15-C1 and 820613-15-C2, labeled 820613-15-C after mixing, whose TGA/DSC is shown in fig. 11, have a mass loss of about 4.44% when heated to 100 ℃; there were endothermic peaks at both 119.8 ℃ (peak temperature) and 135.6 ℃ (onset temperature).

The variable temperature XRPD results for form M are shown in FIG. 12, 1) at N₂Heating to 100 ℃ under protection to obtain a new crystal form: form AH (anhydrous form); 2) the cooled sample was exposed to the environment (RT/. about.40%RH), form AH is reconverted to form M; 3) form M at 30 ℃ N₂Under the purging conditions, one additional diffraction peak (marked by an arrow) was observed in the XRPD pattern.

Example 7: preparation of crystalline form AF

20mg of the EOC317 compound was weighed into 3-mL vials, and 1.0mL of MEK solvent was added, and the mixture was filtered (PTFE filter with a pore size of 0.45 μm) if not completely dissolved. The vial containing the clear solution was sealed with a sealing film and punctured with four small holes on it, left to stand and slowly evaporate at room temperature. And when a solid is separated out, collecting the obtained solid, and heating the obtained solid to 150 ℃ to obtain the crystal form AF. The resulting solid was subjected to XRPD testing, the diffraction pattern of which is shown in FIG. 13

TGA/DSC of form AF, as shown in figure 14, has a mass loss of about 1.1% when heated to 150 ℃, with only one endothermic peak observed at 194.0 ℃ (onset temperature).

Of the crystalline form AF¹HMR is shown in FIG. 15, no significant solvent residue was observed for form AF, TGA/DSC and¹the HMR results suggest that form AF is an anhydrous form.

Example 8: pressure stability test of form A

And respectively applying pressures of 50N, 100N, 150N and 200N to the crystal form A, and testing the influence on the crystal form change after the pressure is applied. The results are shown in fig. 16, where no significant change in crystal form occurred in the samples after the application of different pressures.

Example 9: crystal form a suspension competition test

Suspension competition tests of the crystal form A and the crystal form AF in EtOH at room temperature and 50 ℃ are set, and XRPD results (figure 17) show that the crystal form A is obtained under the two test conditions. Form a is thus thermodynamically more stable than form AF over the range of room temperature to 50 ℃.

Setting crystal form A and crystal form M at ACN/H at room temperature₂Suspension competition tests of O system with different water activities (0, 0.2, 0.4, 0.6 and 0.8 show that the XRPD result (figure 18) shows that the crystal form A is obtained under the condition of water activity of 0-0.8.

Example 10: preparation of form V

20mg of the EOC317 compound was weighed out in a 3mL vial and filtered (0.45 μm pore size PTFE filter) with 1.0mL MeOH added. The vial containing the clear solution was sealed with a sealing film and punctured with four small holes on it, left to stand and slowly evaporate at room temperature. When a solid precipitated, the resulting solid was collected and tested for XRPD.

The XRPD of form V is shown in figure 20 and the TGA/DSC of form V is shown in figure 21, with a mass loss of about 9.4% when heated to 150 ℃; two endothermic peaks of 81.2 ℃ (peak temperature) and 145.9 ℃ (peak temperature) were observed in DSC.¹The HNMR results (fig. 22) show that no significant solvent residue was observed in the form V sample and that form V had a weight loss of 9.4% before 150 ℃, indicating that form V is a hydrate.

Example 11: preparation of form C and form AE

Weighing about 20mg of EOC317 compound pure product, dissolving the pure product with 0.2-1.0 mL of THF solvent, and adding corresponding H into the clear solution₂And O, dropwise adding and stirring until solid is separated out, centrifugally separating the separated solid, and carrying out XRPD test.

The XRPD of form C is shown in figure 23 and the TGA/DSC of form C is shown in figure 24, with a mass loss of about 6.0% when heated to 150 ℃; two endothermic peaks at 86.7 ℃ (peak temperature) and 191.9 ℃ (peak temperature) were observed in DSC.¹The HNMR results (fig. 25) show that no significant solvent residue was observed in the form C sample.

Variable temperature XRPD results for form C are shown in fig. 26, 1) form C at 30 ℃ N₂Transformation to new crystal form under purge conditions: form AH; 2) continued heating to 150 ℃ followed by cooling to 30 ℃ to form a, indicating that form C and form AE are both hydrates.

In summary, the present application provides a new form of EOC317, form a, which is an anhydrous form, form a has better stability than both forms AH and AF (fig. 19 shows XRPD overlay of three anhydrous forms A, AF and AH), and form a exhibits good mechanical stability under different pressure conditions, remains form a after grinding or micronization, and increases the relative humidity from 0% RH to 80% RH at 25 ℃ by 0.11% with almost no moisture absorption by form a.

The application also provides a crystal form M of the EOC317, the crystal form M is a hydrate crystal form, and the crystal form M has better stability and reproducibility (the crystal form C, the crystal form V and the crystal form AE cannot be repeatedly prepared on a large scale) compared with other hydrate crystal forms (such as the crystal form C, the crystal form V and the crystal form AE).

Claims

1. A crystalline form A of a compound of formula I,

2. A crystalline form A of a compound of formula I,

3. A process for the preparation of crystalline form a of the compound of formula I according to any one of claims 1-2.

4. Form M of a compound of formula I containing about 0.2 to 0.6 moles of water,

5. A process for preparing the crystalline form M of the compound of formula I containing about 0.2 to 0.6 moles of water of claim 4 comprising: dissolving the compound shown in the formula I in a solvent, filtering to obtain a filtrate, and cooling the filtrate until a solid is separated out to obtain the crystal form M, wherein the solvent comprises an alcohol solvent, aliphatic halogenated hydrocarbon or a mixed solvent of the solvents.

6. A pharmaceutical composition comprising the crystalline form a of the compound of formula I according to any one of claims 1-2 and/or the crystalline form M of the compound of formula I according to claim 4 containing about 0.2-0.6 mole of water, together with one or more pharmaceutically acceptable excipients.

7. The pharmaceutical composition of claim 6, further comprising one or more immunotherapeutic agents selected from the group consisting of: anti-CTLA 4 antibodies, anti-PD-1 antibodies, and anti-PD-L1 antibodies.

8. Use of the crystalline form a of the compound of formula I according to any one of claims 1-2, the crystalline form M of the compound of formula I according to claim 4 containing about 0.2-0.6 mole of water, or the pharmaceutical composition according to any one of claims 6-7 for the preparation of a medicament for the treatment of cancer.

9. A kit, which may comprise two or more separate pharmaceutical compositions, at least one of which comprises the crystalline form a of the compound of formula I according to any one of claims 1 to 2, the crystalline form M of the compound of formula I according to claim 4 containing about 0.2 to 0.6 mole of water, or the pharmaceutical composition according to any one of claims 6 to 7.

10. A method of inhibiting FGFR and/or VEGFR2, comprising: administering to a subject in need thereof a therapeutically effective amount of the crystalline form a of the compound of formula I of any one of claims 1-2, the crystalline form M of the compound of formula I of claim 4 containing about 0.2-0.6 moles of water, and/or the pharmaceutical composition of any one of claims 6-7.