Solid forms of a pyrido-pyrimidinium inner salt
View Patent ↗Disclosed are solid forms of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt (Compound 1). Methods for the preparation of solid forms of Compound 1 and for the conversion of one solid form of Compound 1 into another are disclosed. Disclosed are compositions for controlling an invertebrate pest comprising a biologically effective amount of a solid form of Compound 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid carriers. Compositions comprising a mixture of a solid form of Compound 1 and at least one other nematocide, insecticide and/or fungicide are also disclosed. Also disclosed are methods for controlling invertebrate pests comprising applying to a plant or seed, or to the environment of the plant or seed, a biologically effective amount of a solid form of Compound 1.
1. A polymorph of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt designated Form A characterized by a room-temperature powder Cu(Kα1)-X-ray diffraction pattern having at least the 2θ reflection positions
2θ
8.036
9.592
13.719
14.453
17.07
23.092
24.027
24.481
29.743
31.831.
2. A polymorph of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt designated Form B characterized by a room-temperature powder Cu(Kα1)-X-ray diffraction pattern having at least the 2θ reflection positions
2θ
6.654
9.41
10.983
11.986
15.513
21.225
22.012
25.638
28.545
40.244.
3. A composition for controlling invertebrate pests comprising (a) the polymorph Form A of claim 1 and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid carriers.
4. A composition for controlling invertebrate pests comprising (a) the polymorph Form A of claim 1 and (b) at least one other nematocide, insecticide or fungicide.
5. A method for preparing the polymorph Form A of claim 1 comprising forming a slurry with a solvent of one or more solid forms of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt selected from the group of Form B, amorphous forms and mixtures of any of the foregoing with Form A, and maintaining the slurry while the solid forms of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt convert to polymorph Form A.
6. The method of claim 5 wherein the solid forms of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt comprises polymorph Form B.
7. The method of claim 5 wherein seed crystals of polymorph Form A of claim 1 are added to the slurry.
8. The method of claim 5 wherein the slurry is agitated.
9. The method of claim 5 wherein the slurry is agitated and heated to a temperature between 30° C. and the boiling point of the solvent.
10. The method of claim 5 wherein the solvent comprises one or more of water, a C 4 -C 8 ester, a C 2 -C 4 alkanol, a C 3 -C 8 ketone, a C 4 -C 8 ether, a C 2 -C 7 nitrile or a C 7 -C 9 aromatic hydrocarbon.
11. The method of claim 10 wherein the solvent comprises one or more of water, ethyl acetate, acetone, acetonitrile or toluene.
12. A method for preparing the polymorph Form A of claim 1 comprising,
(A) contacting 2-(3,5-dichlorophenyl)propanedioyl dichloride and N-[(2-chloro-5-thiazolyl)methyl]-3-methyl-2-pyridinamine in the presence of a first solvent to form a reaction mixture containing an intermediate solid form of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt,
(B) optionally separating the intermediate solid form of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt, and
(C) contacting the intermediate solid form of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt with a second solvent, optionally heated to a temperature between 30° C. and the boiling point of the second solvent, to convert the intermediate solid form to the polymorph Form A of claim 1 .
13. The method of claim 12 wherein the intermediate solid form of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt is Form B of claim 2 .
14. The method of claim 12 wherein in step (C) the intermediate solid form of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt is contacted with seed crystals of polymorph Form A of claim 1 .
15. The method of claim 12 wherein the first and second solvent comprises toluene and the second solvent is heated to a temperature between 90° C. and 110° C.
16. A method for preparing the polymorph Form A of claim 1 comprising, contacting 2-(3,5-dichlorophenyl)propanedioyl dichloride and N-[(2-chloro-5-thiazolyl)methyl]-3-methyl-2-pyridinamine in the presence of a solvent optionally heated to a temperature between 30° C. and the boiling point of the solvent to form a reaction mixture containing polymorph Form A of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H -pyrido[1,2-a]pyrimidinium inner salt.
17. The method of claim 16 wherein the solvent comprises dichloromethane.
18. A method for controlling invertebrate pests comprising applying to the plant or seed, or to the environment of the plant or seed, a biologically effective amount of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidinium inner salt comprising the polymorph Form A of claim 1 .