# US 10,766,862 B2 · Crystal form and salt form of and preparation method for tyrosine kinase inhibitor

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- Number: US 10,766,862 B2
- Document ID: US10766862B2
- Status: Granted
- Kind: B2
- Application number: 16/337,874
- Filed: 2017-09-29
- Published: 2020-01-23
- Granted: 2020-09-08
- Earliest claimed: 2016-09-30
- Assignees: Guangdong Raynovent Biotech Co., Ltd.
- Applicants: Guangdong Raynovent Biotech Co., Ltd.
- Inventors: Chaofeng Long; Zhengxia Chen; Xiaoxin Chen; Yang Zhang; Zhuowei Liu; Shuhui Chen; Jian Li
- Web page: https://patentgrep.com/patent/US10766862B2

## CPC

- C07D 215/233: only one oxygen atom which is attached in position 4
- C07D 215/48: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- A61K 31/47: Quinolines; Isoquinolines
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

Disclosed are a crystal form and a salt form of and a preparation method for a tyrosine kinase inhibitor.

## Claims

### Claim 1

A crystal form of Compound 1 comprising a crystal form A, a crystal form B, a crystal form C, a crystal form D or a crystal form E,
wherein,
the crystal form A has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 4.47±0.2°, 7.80±0.2°, 12.61±0.2°, 13.25±0.2°, 16.32±0.2°;
the crystal form B has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 13.55±0.2°, 15.94±0.2°, 17.36±0.2°, 22.41±0.2°, 24.16±0.2°, 24.78±0.2°;
the crystal form C has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 13.29±0.2°, 15.58±0.2°, 16.21±0.2°, 19.84±0.2°, 24.95±0.2°;
the crystal form D has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 6.70±0.2°, 11.30±0.2°, 11.76±0.2°, 15.52±0.2°, 16.35±0.2°;
the crystal form E has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 4.51±0.2°, 6.68±0.2°, 11.79±0.2°, 13.62±0.2°.

### Claim 2 (depends on 1)

The crystal form of Compound 1 according to claim 1, wherein
the crystal form A further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 4.47±0.2°, 7.80±0.2°, 8.87±0.2°, 12.61±0.2°, 13.25±0.2°, 16.32±0.2°, 19.03±0.2°, 26.66±0.2°;
the crystal form B further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 13.55±0.2°, 15.94±0.2°, 17.36±0.2°, 22.41±0.2°, 24.16±0.2°, 24.78±0.2°, 25.19±0.2°;
the crystal form C further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 13.29±0.2°, 15.58±0.2°, 16.21±0.2°, 19.84±0.2°, 24.32±0.2°, 24.95±0.2°, 28.13±0.2°;
the crystal form D further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 6.70±0.2°, 11.30±0.2°, 11.76±0.2°, 15.52±0.2°, 16.35±0.2°, 27.26±0.2°;
the crystal form E further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 4.51±0.2°, 6.68±0.2°, 11.79±0.2°, 13.62±0.2°, 15.51±0.2°.

### Claim 3 (depends on 2)

The crystal form of Compound 1 according to claim 2, wherein
the crystal form A has an XRPD pattern as shown in FIG. 1;
the crystal form B has an XRPD pattern as shown in FIG. 3;
the crystal form C has an XRPD pattern as shown in FIG. 6;
the crystal form D has an XRPD pattern as shown in FIG. 9;
the crystal form E has an XRPD pattern as shown in FIG. 12.

### Claim 4

A hydrochloride salt of Formula (I) comprising a crystal form F having an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 11.64±0.2°, 13.32±0.2°, 14.02±0.2°, 20.06±0.2°, 24.22±0.2°

### Claim 5 (depends on 4)

The hydrochloride salt of Formula (I) according to claim 4, wherein the crystal form F further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 11.64±0.2°, 13.32±0.2°, 14.02±0.2°, 16.78±0.2°, 20.06±0.2°, 24.22±0.2°, 25.02±0.2°.

### Claim 6 (depends on 5)

The hydrochloride salt of Formula (I) according to claim 5, wherein the crystal form F has an XRPD pattern as shown in FIG. 15.

### Claim 7

A p-toluenesulfonate salt of Formula (II) comprising a crystal form G having an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 4.84±0.2°, 9.93±0.2°, 15.43±0.2°, 19.48±0.2°, 19.93±0.2°

### Claim 8 (depends on 7)

The p-toluenesulfonate salt of Formula (II) according to claim 7, wherein the crystal form G further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 4.84±0.2°, 9.93±0.2°, 15.43±0.2°, 19.48±0.2°, 19.93±0.2°, 20.56±0.2°, 24.20±0.2°, 24.89±0.2°.

### Claim 9 (depends on 8)

The p-toluenesulfonate salt of Formula (II) according to claim 8, wherein the crystal form G has an XRPD pattern as shown in FIG. 18.

### Claim 10

An ethanesulfonate salt of Formula (III) comprising a crystal form H having an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 7.80±0.2°, 12.53±0.2°, 13.11±0.2°, 17.78±0.2°, 21.90±0.2°

### Claim 11 (depends on 10)

The ethanesulfonate salt of Formula (III) according to claim 10, wherein the crystal form H further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 7.80±0.2°, 12.53±0.2°, 13.11±0.2°, 14.86±0.2°, 17.78±0.2°, 20.11±0.2°, 21.90±0.2°.

### Claim 12 (depends on 11)

The ethanesulfonate salt of Formula (III) according to claim 11, wherein the crystal form H has an XRPD pattern as shown in FIG. 21.

### Claim 13

A methanesulfonate salt of Formula (IV) comprising a crystal form J, a crystal form K, a crystal form L or a crystal form M, wherein,
the crystal form J has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 7.88±0.2°, 12.58±0.2°, 15.02±0.2°, 21.28±0.2°, 22.00±0.2°, 27.35±0.2°;
the crystal form K has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 8.02±0.2°, 16.52±0.2°, 18.10±0.2°, 20.35±0.2°, 22.10±0.2°, 23.27±0.2°;
the crystal form L has an X-ray powder diffraction pattern with characteristic diffraction peaks at angle 2θ of: 18.06±0.2°, 21.35±0.2°, 22.05±0.2°, 24.94±0.2°;
the crystal form M has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 9.68±0.2°, 20.78±0.2°, 23.15±0.2°, 29.82±0.2°.

### Claim 14 (depends on 13)

The methanesulfonate salt of Formula (IV) according to claim 13, wherein,
the crystal form J further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 7.88±0.2°, 12.58±0.2°, 15.02±0.2°, 16.42±0.2°, 20.41±0.2°, 21.28±0.2°, 22.00±0.2°, 27.35±0.2°;
the crystal form K further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 8.02±0.2°, 15.14±0.2°, 16.52±0.2°, 18.10±0.2°, 20.35±0.2°, 21.36±0.2°, 22.10±0.2°, 23.27±0.2°;
the crystal form L further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 8.00±0.2°, 15.10±0.2°, 16.49±0.2°, 18.06±0.2°, 20.49±0.2°, 21.35±0.2°, 22.05±0.2°, 24.94±0.2°;
the crystal form M further has an X-ray powder diffraction pattern with characteristic diffraction peaks at angles 2θ of: 9.68±0.2°, 17.37±0.2°, 18.24±0.2°, 20.19±0.2°, 20.78±0.2°, 22.10±0.2°, 22.74±0.2°, 23.15±0.2°, 29.82±0.2°.

### Claim 15 (depends on 14)

The methanesulfonate salt of Formula (IV) according to claim 14, wherein
the crystal form J has an XRPD pattern as shown in FIG. 24;
the crystal form K has an XRPD pattern as shown in FIG. 27;
the crystal form L has an XRPD pattern as shown in FIG. 29;
the crystal form M has an XRPD pattern as shown in FIG. 31.