# US 10,766,876 B2 · Cocrystal, production method thereof, and medicament containing cocrystal

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- Number: US 10,766,876 B2
- Document ID: US10766876B2
- Status: Granted
- Kind: B2
- Application number: 15/388,063
- Filed: 2016-12-22
- Published: 2017-06-29
- Granted: 2020-09-08
- Earliest claimed: 2015-12-24
- Assignees: Takeda Pharmaceutical Company Limited
- Applicants: Takeda Pharmaceutical Company Limited
- Inventors: Koya Kimoto; Mitsuo Yamamoto; Masato Kitayama; Yasuhiro Sawai; Miyuki Hohokabe; Kentaro Iwata
- Web page: https://patentgrep.com/patent/US10766876B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61K 31/4725: containing further heterocyclic rings
- C07C 55/08: Malonic acid
- C07C 57/145: Maleic acid
- C07C 59/245: containing hydroxy or O-metal groups
- C07C 59/265: Citric acid
- C07C 59/50: Mandelic acid
- C07C 59/54: containing six-membered aromatic rings and other rings
- C07C 65/05: o-Hydroxy carboxylic acids
- C07C 65/10: Salicylic acid
- 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)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present invention provides a cocrystal of (S)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one and an organic acid capable of forming a cocrystal with the compound.

## Claims

### Claim 1

A cocrystal of (S)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one and gentisic acid, wherein the cocrystal shows a powder X-ray diffraction pattern having characteristic peaks at lattice spacings (d) of 13.04±0.2, 5.96±0.2, 4.67±0.2, 3.63±0.2 and 3.28±0.2 angstroms.

### Claim 2 (depends on 1)

The cocrystal according to claim 1, wherein a molar ratio of (S)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one and gentisic acid ((S)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one:gentisic acid) is 1:1.

### Claim 3 (depends on 1)

A method of producing the cocrystal according to claim 1, comprising mixing and stirring a strongly basic aqueous solution of (S)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one, and a solution of gentisic acid.

### Claim 4 (depends on 3)

The production method according to claim 3, wherein the gentisic acid in the mixed solution of the strongly basic aqueous solution of (S)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one and the solution of the gentisic acid has a concentration of 0.298-0.592 mol/L.

### Claim 5 (depends on 3)

The production method according to claim 3, wherein the gentisic acid in the mixed solution of the strongly basic aqueous solution of (S)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one and the solution of the gentisic acid has a concentration of 0.388-0.592 mol/L.

### Claim 6 (depends on 3)

The production method according to claim 3, wherein a solvent of the solution of the gentisic acid is
(i) water,
(ii) at least one organic solvent selected from the group consisting of isopropyl alcohol, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, methanol, ethanol, 1-propanol, tetrahydrofuran, acetone, 2,2,2-trifluoroethanol, acetonitrile, 1-methyl-2-pyrrolidone, and acetic acid, or
(iii) a mixed solvent of at least one organic solvent selected from the group described in (ii) and water.

### Claim 7 (depends on 3)

The production method according to claim 3, comprising adding, as a seed crystal, a cocrystal of (S)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one and gentisic acid to the mixture of the strongly basic aqueous solution of (S)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5 (4H)-one and the solution of the gentisic acid.

### Claim 8 (depends on 1)

The cocrystal according to claim 1, wherein the cocrystal shows a powder X-ray diffraction pattern having characteristic peaks at lattice spacings (d) of 13.04±0.2, 10.92±0.2, 9.97±0.2, 5.96±0.2, 4.67±0.2, 3.63±0.2 and 3.28±0.2 angstroms.

### Claim 9 (depends on 1)

The cocrystal according to claim 1, wherein the cocrystal shows a powder X-ray diffraction pattern having characteristic peaks at lattice spacings (d) of 13.04±0.2, 10.92±0.2, 9.97±0.2, 6.14±0.2, 5.96±0.2, 5.28±0.2, 4.67±0.2, 3.63±0.2 and 3.28±0.2 angstroms.

### Claim 10 (depends on 1)

The cocrystal according to claim 1, wherein the cocrystal is a nonhydrate.