# US 10,308,641 B2 · Crystal form of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxole-5-yl)cyclopropane formamido)-3-methylpyridine-2-yl)benzoic acid and preparation method thereof

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- Number: US 10,308,641 B2
- Document ID: US10308641B2
- Status: Granted
- Kind: B2
- Application number: 15/751,205
- Filed: 2016-08-11
- Published: 2018-08-16
- Granted: 2019-06-04
- Earliest claimed: 2015-08-11
- Assignees: Crystal Pharmatech Co., Ltd.
- Applicants: Crystal Pharmatech Co., Ltd.
- Inventors: Minhua Chen; Yanfeng Zhang; Kai Liu; Po Zou; Xiaoyu Zhang
- Web page: https://patentgrep.com/patent/US10308641B2

## CPC

- C07D 405/12: linked by a chain containing hetero atoms as chain links
- A61K 31/443: containing a five-membered ring with oxygen as a ring hetero atom
- A61K 31/47: Quinolines; Isoquinolines
- A61P 11/00: Drugs for disorders of the respiratory system
- 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

The present disclosure provides crystalline form A of 3-(6-(1-(2, 2-difluorobenzo [d] [1, 3] dioxo-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid and process of preparation thereof. The crystalline form A has low hygroscopicity, good stability, is convenient to store. It has higher solubility than that of prior art and therefore plays an important role in further optimization and development of the drug.

## Claims

### Claim 1

A crystalline Form A of compound of formula (I),
wherein the X-ray powder diffraction pattern shows characteristic peaks at 2theta values of 8.8°±0.2°, 9.8°±0.2°, 10.6°±0.2°, 16.2°±0.2°, 18.1°±0.2°, 20.0°±0.2°, 21.2°±0.2°, 22.2°±0.2° 23.5°±0.2°.

### Claim 2 (depends on 1)

A process of preparing crystalline Form A of compound of formula (I) according to claim 1, comprising dissolving compound of formula (I) in methyl isobutyl ketone or the mixture of acetone or methyl isobutyl ketone and methyl tertiary butyl ether, and obtaining a white solid by evaporation at the temperature of 20° C.-80° C., wherein the volume ratio of acetone or methyl isobutyl ketone and methyl tertiary butyl ether is 1:1 to 1:4.

### Claim 3 (depends on 2)

The process according to claim 2, wherein said temperature is 30° C.˜70° C.

### Claim 4 (depends on 3)

The process according to claim 3, wherein said temperature is 40° C.˜60° C.

### Claim 5 (depends on 1)

A pharmaceutical composition, wherein the said pharmaceutical composition comprises a therapeutically effective amount of crystalline Form A according to claim 1 and pharmaceutically acceptable excipient.

### Claim 6 (depends on 1)

A method of treating cystic fibrosis in a subject thereof, comprising administering the crystalline Form A according to claim 1 to the subject.

### Claim 7 (depends on 1)

A method of treating cystic fibrosis in a subject thereof, comprising administering the crystalline Form A according to claim 1 to the subject in combination with one or more drugs.

### Claim 8 (depends on 1)

A method of treating cystic fibrosis in a subject thereof, comprising administering the crystalline Form A according to claim 1 to the subject in combination with Ivacaftor.