Cocrystal, production method thereof, and medicament containing cocrystal
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.
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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. The cocrystal according to claim 1 , wherein the cocrystal is a nonhydrate.