IP Library › Granted Patent US 9,187,463
Granted Patent B2
US 9,187,463 · App. 14/118,377 · Granted Nov 17, 2015

Polymorph form of 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid

Inventors: Toyoharu Numata (Aichi, JP); Hirohide Noguchi (Aichi, JP); Nobuaki Waizumi (Osaka, JP); Takashi Kojima (Kanagawa, JP)
Assignee: RAQUALIA PHARMA INC.
C07D413/14
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Quick Facts
Patent No.
US 9,187,463
App. No.
14/118,377
Filed
Jan 16, 2014
Granted
Nov 17, 2015
Kind
B2
Art Unit
1625
USPC
546/198
Abstract

The present invention relates to novel crystal forms of 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid. More particularly, the invention relates to polymorph forms (Polymorph Form I or Polymorph Form II), and to processes for the preparation of, compositions containing and to uses of, such polymorph forms.

Claims (10)

1. 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form I, which is characterized by a powder X-ray diffraction pattern (PXRD) obtained by irradiation with Cu-Kα radiation which includes main peaks at 2-Theta° 5.9, 9.3, 9.8, 11.9, 13.7, 14.3, 15.0, 17.8, 18.2-19.3, 19.7, 22.6, 23.4-24.5 and 24.9+/−0.2.

2. 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form I as described in claim 1 , which is further characterized by differential scanning calorimetry (DSC) in which it exhibits an endothermic event at about 169° C.

3. 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form I as described in claim 1 , which is further characterized by an infrared (IR) spectrum (KBr) which shows absorption bands at 2948, 1723, 1615, 1535, 1506, 1437, 1383, 1366, 1287, 1262, 1245, 1180, 1164, 1120, 1095, 1059, 1032, 992, 974, 935, 918, 869, 858, 828, 784, 746, 732, 654 and 556+/−2 cm −1 .

4. 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form II, which is characterized by a powder X-ray diffraction pattern (PXRD) obtained by irradiation with Cu-Kα radiation which includes main peaks at 2-Theta° 5.8, 9.7, 10.5, 11.8, 12.4, 13.5, 14.2, 14.6-14.9, 15.4, 17.8, 18.2, 19.9-20.5, 21.2, 21.8, 23.6, 24.1 and 24.6+/−0.2.

5. 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form II as described in claim 4 , which is further characterized by differential scanning calorimetry (DSC) in which it exhibits an endothermic event at about 167-169° C.

6. 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form II, as described in claim 4 , which is further characterized by an infrared (IR) spectrum (KBr) which shows absorption bands at 2950, 1724, 1614, 1534, 1507, 1438, 1383, 1366, 1287, 1262, 1245, 1180, 1164, 1121, 1095, 1059, 1031, 992, 974, 935, 918, 869, 857, 828, 784, 746, 732, 654 and 555+/−2 cm −1 .

7. A pharmaceutical composition including 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form as described in claim 1 or claim 4 , together with one or more pharmaceutically acceptable excipients.

8. 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form as described in claim 1 or claim 4 for use as a medicament.

9. A process for preparing 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form I as described in claim 1 , comprising the step of recrystallizing 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid from ethyl acetate and a mixture of organic solvents which can be mixed with ethyl acetate.

10. A process for preparing 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form II as described in claim 4 , comprising the steps of placing 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid on 110° C. or higher temperature, and then cooling down to room temperature under ambient conditions.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 16, 2014
From: NUMATA, TOYOHARU; NOGUCHI, HIROHIDE; WAIZUMI, NOBUAKI; KOJIMA, TAKASHI
To: RAQUALIA PHARMA INC.
Reel/Frame 031986/0261 →
Priority Claims (1)
JP 2011-111901 · May 18, 2011 · national
Continuity (1)
Related Publication 20140187583A1 · Jul 3, 2014