Solid forms of an azocyclic amide
Disclosed are solid forms of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone (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 fungicidal compositions comprising a fungicidally 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 fungicide or insecticide are also disclosed. Also disclosed are methods for controlling plant diseases caused by fungal plant pathogens comprising applying to a plant or portion thereof, or to a plant seed, a fungicidally effective amount of a solid form of Compound 1.
1. A crystalline form of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone designated Form B having a powder Cu(Kα) X-ray diffraction pattern substantially in accordance with that shown in FIG. 2 .
2. The crystalline form of claim 1 characterized by a powder Cu(Kα) X-ray diffraction pattern having at least the 2θreflection positions 14.902, 18.123, 18.87, 20.204, 20.883, 21.79, 24.186 and 26.947.
3. A method for preparing the crystalline form of claim 1 comprising forming a reaction mixture by contacting 2-bromo-1-[4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazoly]ethanone and 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinecarbothioamide in the presence of an alkanol solvent selected from methanol and ethanol, including mixtures thereof; neutralizing the reaction mixture with base; and adding up to 50% water by volume and seed crystals of the crystalline form of claim 1 to the reaction mixture.
4. A method for preparing the crystalline form of claim 1 comprising mixing a crystalline form of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone designated Form A having a powder Cu(Kα) X-ray diffraction pattern substantially in accordance with that shown in FIG. 1 with a solvent comprising an alkanol selected from methanol and ethanol, including mixtures thereof, and optionally up to about 30% water by volume to form a slurry; adding seed crystals of the crystalline form of claim 1 to the slurry; and maintaining the slurry while Form A converts to the crystalline form of claim 1 .
5. The method of claim 4 wherein the slurry consists essentially of a mixture of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone with methanol or with methanol and water, or consists essentially of a mixture of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone with ethanol or with ethanol and water.
6. The method of claim 4 wherein the crystalline Form A mixed with the solvent is in admixture with the crystalline form of claim 1 .
7. A fungicidal composition comprising (a) a fungicidally effective amount of the the crystalline form as defined by claim 1 and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid carriers.
8. The fungicidal composition of claim 7 comprising a liquid carrier forming a continuous liquid phase in which component (a) is dispersed.
9. The fungicidal composition of claim 8 wherein the liquid carrier forming the continuous liquid phase contains at least about 50% water by weight of the liquid carrier.
10. The fungicidal composition of claim 9 further comprising a water-immiscible liquid component emulsified in the continuous liquid phase.
11. The fungicidal composition of claim 8 wherein the liquid carrier forming the continuous liquid phase is water-immiscible.
12. A method for controlling plant diseases caused by Oomycete fungal plant pathogens comprising applying to a plant or portion thereof, or to a plant seed, a fungicidally effective amount of the crystalline form as defined by claim 1 .