# US 11,306,086 B2 · Crystalline salts of a B-RAF kinase inhibitor

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- Number: US 11,306,086 B2
- Document ID: US11306086B2
- Status: Granted
- Kind: B2
- Application number: 16/759,187
- Filed: 2018-10-26
- Published: 2020-09-10
- Granted: 2022-04-19
- Earliest claimed: 2017-10-26
- Assignees: Xynomic Pharmaceuticals, Inc.
- Applicants: Xynomic Pharmaceuticals, Inc.
- Inventors: Ulrike Werthmann; Gerd-Michael Maier; Bodo Betzemeier; Otmar Schaaf
- Web page: https://patentgrep.com/patent/US11306086B2

## CPC

- C07D 471/04: Ortho-condensed systems
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present invention is related to crystalline salts of N-(3-(5-((1-ethylpiperidin-4-yl)(methyl)amino)-3-(pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-2,4-difluorophenyl)propane-1-sulfonamide, a RAF kinase Inhibitor, useful in the treatment of cancer and other diseases.

## Claims

### Claim 1

Crystalline N-(3-(5-((1-ethylpiperidin-4-yl)(methyl)amino)-3-(pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-2,4-difluorophenyl)propane-1-sulfonamide monosuccinate salt, having an X-ray powder diffraction pattern comprising at least one of the following peaks, in terms of 2θ: 15.4°±0.5°; 20.0°±0.5°; and 21.8°±0.5°.

### Claim 2 (depends on 1)

The crystalline salt of claim 1 which is substantially anhydrous and non-solvated.

### Claim 3 (depends on 1)

The crystalline salt of claim 1, having an X-ray powder diffraction pattern comprising a peak, in terms of 2θ, at 15.4°±0.5°.

### Claim 4 (depends on 1)

The crystalline salt of claim 1, having an X-ray powder diffraction pattern comprising the following peaks, in terms of 2θ: 15.4°±0.5°; 20.0°±0.5°; and 21.8°±0.5°.

### Claim 5 (depends on 1)

The crystalline salt of claim 1 having an X-ray powder diffraction pattern substantially as shown in FIG. 10, FIG. 26, or FIG. 38.

### Claim 6 (depends on 1)

The crystalline salt of claim 1 having a differential scanning calorimetry thermogram (DSC) substantially as shown in FIG. 11, FIG. 27, or FIG. 39.

### Claim 7 (depends on 1)

The crystalline salt of claim 1 having a thermogravimetric analysis (TGA) substantially as shown in FIG. 12, FIG. 28 or FIG. 39.

### Claim 8 (depends on 1)

A composition comprising the crystalline salt of claim 1.

### Claim 9 (depends on 8)

The composition of claim 8 wherein the composition comprises at least one pharmaceutically acceptable carrier.

### Claim 10 (depends on 9)

The composition of claim 9, wherein the composition is a tablet.

### Claim 11 (depends on 1)

A process for preparing the crystalline salt of claim 1 comprising reacting N-(3-(5-((1-ethylpiperidin-4-yl)(methyl)amino)-3-(pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl)-2,4-difluorophenyl)propane-1-sulfonamide with one equivalent of succinic acid.

### Claim 12 (depends on 11)

The process of claim 11 further comprising crystallizing the salt from a C1-4 alcohol or aqueous C1-4 alcohol or ethyl acetate.

### Claim 13 (depends on 11)

The process of claim 11 further comprising crystallizing the salt from ethanol, isopropanol, aqueous ethanol, aqueous isopropanol, or ethyl acetate.

### Claim 14 (depends on 1)

A method of treating a cancer in a patient, comprising administering to the patient a therapeutically effective amount of a crystalline salt of claim 1, wherein the cancer is breast cancer, prostate cancer, colon cancer, endometrial cancer, brain cancer, bladder cancer, skin cancer, uterus cancer, ovarian cancer, lung cancer, pancreatic cancer, renal cancer, gastric cancer, hematological cancer, malignant melanoma, thyroid cancer, colorectal cancer, or biliary tract cancer.

### Claim 15 (depends on 14)

The method of claim 14, wherein the cancer is lung cancer.

### Claim 16 (depends on 14)

The method of claim 14, wherein the cancer is malignant melanoma.

### Claim 17 (depends on 14)

The method of claim 14, wherein the cancer is thyroid cancer.

### Claim 18 (depends on 14)

The method of claim 14, wherein the cancer is colorectal cancer.

### Claim 19 (depends on 14)

The method of claim 14, wherein the cancer is biliary tract cancer.

### Claim 20 (depends on 14)

The method of claim 14, wherein the cancer is non-small cell lung cancer.