Claims for Patent: 6,225,474

Summary for Patent: 6,225,474

Title:	Polymorphs of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid and method of producing the same
Abstract:	The present invention provides a technique of selectively producing a desired polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid. The present invention also provides a method of producing various polymorphs of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which comprises crystallizing under the conditions defined by a specific temperature and a composition of a mixed solvent of methanol and water, and polymorphs obtained by the method. The present invention further provides a method of producing the other polymorphs or amorphous compounds by drying a specific polymorph under a reduced pressure with heating, and the other polymorphs or amorphous compounds obtained by the method.
Inventor(s):	Matsumoto; Koichi (Iwakuni, JP), Watanabe; Kenzo (Iwakuni, JP), Hiramatsu; Toshiyuki (Iwakuni, JP), Kitamura; Mitsutaka (Higashi-Hiroshima, JP)
Assignee:	Teijin Limited (Osaka, JP)
Application Number:	09/485,861
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,225,474
Patent Claims:	1. A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which shows a X-ray powder diffraction pattern having characteristic peaks at a reflection angle 2.theta. of about 6.62, 7.18, 12.80, 13.26, 16.48, 19.58, 21.92, 22.68, 25.84, 26.70, 29.16 and 36.70.degree.. 2. A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which shows a X-ray powder diffraction pattern having characteristic peaks at a reflection angle 2.theta. of about 6.76, 8.08, 9.74, 11.50, 12.22, 13.56, 15.76, 16.20, 17.32, 19.38, 21.14, 21.56, 23.16, 24.78, 25.14, 25.72, 26.12, 26.68, 27.68 and 29.36.degree.. 3. A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which shows a X-ray powder diffraction pattern having characteristic peaks at a reflection angle 2.theta. of about 6.62, 10.82, 13.36, 15.52, 16.74, 17.40, 18.00, 18.70, 20.16, 20.62, 21.90, 23.50, 24.78, 25.18, 34.08, 36.72 and 38.04.degree.. 4. A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which shows a X-ray powder diffraction pattern having characteristic peaks at a reflection angle 2.theta. of about 8.32, 9.68, 12.92, 16.06, 17.34, 19.38, 21.56, 24.06, 26.00, 30.06, 33.60 and 40.34.degree.. 5. A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which shows a X-ray powder diffraction pattern having characteristic peaks at a reflection angle 2.theta. of about 6.86, 8.36, 9.60, 11.76, 13.74, 14.60, 15.94, 16.74, 17.56, 20.00, 21.26, 23.72, 24.78, 25.14, 25.74, 26.06, 26.64, 27.92, 28.60, 29.66 and 29.98.degree.. 6. A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid having a characteristic absorption, which can be distinguished from that of other polymorphs, at about 1678 cm.sup.-1 in infrared spectroscopic analysis. 7. A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid having characteristic absorptions, which can be distinguished from that of other polymorph, at about 1715, 1701 and 1682 cm.sup.-1 in infrared spectroscopic analysis. 8. A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid having characteristic absorptions, which can be distinguished from that of other polymorph, at about 1703 and 1219 cm.sup.-1 in infrared spectroscopic analysis. 9. A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid having a characteristic absorption, which can be distinguished from that of other polymorph, at about 1705 cm.sup.- in infrared spectroscopic analysis. 10. A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid having characteristic absorptions, which can be distinguished from that of other polymorph, at about 1703 and 1684 cm.sup.-1 in infrared spectroscopic analysis. 11. An amorphous compound of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid. 12. A polymorph obtained by crystallizing 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid under the conditions shown as the region I in FIG. 1, which are defined by a temperature and a composition of a mixed solvent of methanol and water. 13. A polymorph obtained by crystallizing 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid under the conditions shown as the region II in FIG. 1, which are defined by a temperature and a composition of a mixed solvent of methanol and water. 14. A polymorph obtained by crystallizing 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid under the conditions shown as the region III in FIG. 1, which are defined by a temperature and a composition of a mixed solvent of methanol and water. 15. A polymorph obtained by drying crystal G of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid under a reduced pressure with heating. 16. A polymorph obtained by heating 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid suspended in a mixed solvent of methanol and water in the presence of a small amount of a crystal C of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid. 17. A polymorph obtained by crystallizing 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid from a mixed solvent of 2-propanol and water. 18. A polymorph obtained by air-drying crystal D of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid under a normal atmosphere. 19. An amorphous compound obtained by drying crystal D of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid under a reduced pressure with heating. 20. A method of producing crystal A of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which comprises crystallizing under the conditions shown as region I in FIG. 1, which are defined by a temperature and a composition of a mixed solvent of methanol and water, wherein region I is an area surrounded by lines defined by Y=-0.2X+85; Y=1.0X-31; and Y=-3.3X+273, wherein X is methanol/water composition (U/V %), and Y is temperature (.degree. C.). 21. A method of producing crystal B of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which comprises drying crystal G of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid under a reduced pressure with heating. 22. A method of producing crystal C of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which comprises heating 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid suspended in a mixed solvent of methanol and water in the presence of a small amount of crystal C of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid. 23. A method of producing crystal D of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which comprises crystallizing under the conditions shown as region II in FIG. 1, which are defined by a temperature and a composition of a mixed solvent of methanol and water, wherein region II is an area surrounded by lines defined by Y=--0.2X+85; Y=1.0X-31; Y=20; and X=100, wherein X is methanol/water composition (U/V %), and Y is temperature (.degree. C.). 24. A method of producing crystal G of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which comprises crystallizing under the conditions shown as region III in FIG. 1, which are defined by a temperature and a composition of a mixed solvent of methanol and water, wherein region III is an area surrounded by lines defined by Y=--0.2X+85; Y=1.0X-31; Y=-3.3X+273; and X=50, wherein X is methanol/water composition (U/V %), and Y is temperature (.degree. C.). 25. A method of producing crystal G of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which comprises crystallizing from a mixed solvent of 2-propanol and water. 26. A method of producing crystal G of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which comprises air-drying crystal D of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid under a normal atmosphere. 27. A method of producing an amorphous compound of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which comprises drying crystal D of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid under a reduced pressure with heating.