# US 11,028,069 B2 · Salt of substituted piperidine compound

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- Number: US 11,028,069 B2
- Document ID: US11028069B2
- Status: Granted
- Kind: B2
- Application number: 16/472,000
- Filed: 2017-12-22
- Published: 2020-03-19
- Granted: 2021-06-08
- Earliest claimed: 2016-12-22
- Assignees: Taiho Pharmaceutical Co., Ltd.
- Applicants: Taiho Pharmaceutical Co., Ltd.
- Inventors: Morihiro Mitsuya
- Web page: https://patentgrep.com/patent/US11028069B2

## CPC

- A61P 35/00: Antineoplastic agents
- C07D 401/14: containing three or more hetero rings
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

An object of the present invention is to provide a salt of the compound 1-(2,3-dichlorobenzoyl)-4-((5-fluoro-6-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid, useful as an antitumor agent, and crystals thereof which are excellent in solubility, stability, and oral absorption and can be produced in large quantities. The present invention relates to a hydrochloride salt of 1-(2,3-dichlorobenzoyl)-4-((5-fluoro-6-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid and crystals of the hydrochloride salt having characteristic peaks at particular diffraction angles in powder X-ray diffraction spectrum.

## Claims

### Claim 1

A hydrochloride salt of 1-(2,3-dichlorobenzoyl)-4-((5-fluoro-6-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid,
wherein the salt is a crystal having characteristic peaks at at least 3 or more diffraction angles (2θ±0.2°) selected from 12.83°, 13.54°, 16.20°, 18.27°, 23.80°, 29.10°, and 32.83° in powder X-ray diffraction spectrum.

### Claim 2 (depends on 1)

The salt according to claim 1, wherein the salt is a crystal having characteristic peaks at diffraction angles (2θ±0.2°) of 12.83°, 13.54°, 16.20°, 18.27°, 23.80°, 29.10°, and 32.83° in powder X-ray diffraction spectrum.

### Claim 3 (depends on 1)

The salt according to claim 1, wherein the salt has an endothermic peak at 234±5° C. in differential thermal analysis.

### Claim 4 (depends on 1)

The salt according to claim 1, wherein a weight ratio is 90% or more.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising:
the salt according to claim 1; and
a pharmaceutical carrier.

### Claim 6 (depends on 5)

The composition according to claim 5, wherein the composition is suitable for oral administration.

### Claim 7 (depends on 1)

A method for producing a hydrochloride salt of 1-(2,3-dichlorobenzoyl)-4-((5-fluoro-6-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid according to claim 1, the method comprising:
adding 1-(2,3-dichlorobenzoyl)-4-((5-fluoro-6-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid and hydrochloric acid to a solvent; and
stirring the solvent obtained in the adding to precipitate a hydrochloride salt of 1-(2,3-dichlorobenzoyl)-4-((5-fluoro-6-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)piperidine-4-carboxylic acid.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the solvent in the adding is selected from a C1-6 alcohol, a C1-6 ester, a C1-6 ketone, or a mixed solvent thereof.

### Claim 9 (depends on 7)

The method according to claim 7, wherein the solvent in adding is selected from the group consisting of water, a C1-6 alcohol, a C1-6 ester, a C1-6 ketone, a C1-6 ether, a C1-6 hydrocarbon, an aprotic polar solvent, and an aqueous hydrogen halide solution.