Crystalline forms and processes for the preparation of phenyl-pyrazoles useful as modulators of the 5-HT;serotonin receptor

• US 9,199,940 B2
• Filed: 07/03/2013
• Issued: 12/01/2015
• Est. Priority Date: 05/18/2006
• Status: Active Grant

• Current Assignee: Arena Pharmaceuticals Incorporated (Pfizer Inc.)
• Original Assignee: Arena Pharmaceuticals Incorporated (Pfizer Inc.)
• Inventors: Gharbaoui, Tawfik, Sengupta, Dipanjan, Krishnan, Ashwin M., Shah, Nainesh, Hart, Ryan M., Macias, Mark, Lally, Edward A.
• Primary Examiner(s): Otton, Alicia L
• Application Number:
  US13/935,329
• Publication Number:
  US 20130296321A1
• Time in Patent Office: 881 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

Abstract

The present invention relates to processes for preparing phenyl-pyrazoles of Formula (I) and salts and pharmaceutical compositions thereof, useful as modulators of 5-HT_2A serotonin receptor activity.

The present invention also relates to intermediates used in the processes, and their preparation. The present invention also relates to crystalline forms of 5-HT_2A serotonin receptor modulators, compositions thereof and methods of using the same.

Claims

1. A crystalline form of 4-(2-(4-(3-methoxybenzamido)-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)ethyl)morpholin-4-ium chloride (Form I) having an X-ray powder diffraction pattern, generated with CuKα

radiation, comprising a peak, in terms of 2 θ

, at about 14.4°

.

2. The crystalline form of claim 1 having an X-ray powder diffraction pattern, generated with CuKα

radiation, further comprising a peak, in terms of 2 θ

, at about 5.2°

.

3. The crystalline form according to claim 1-having an X-ray powder diffraction pattern, generated with CuKα

radiation, further comprising a peak, in terms of 2 θ

, at about 25.6°

.

4. The crystalline form according to claim 1 having an X-ray powder diffraction pattern, generated with CuKα

radiation, further comprising peaks, in terms of 2 θ

, at about 5.2° and

about 25.6°

.

5. The crystalline form according to claim 1 having an X-ray powder diffraction pattern, generated with CuKα

radiation, further comprising peaks, in terms of 2 θ

, at about 5.2°

, about 25.6°

, about 17.3°

, about 27.1°

, about 15.8°

, and about 20.1°

.

6. The crystalline form according to claim 1 having an X-ray powder diffraction pattern, generated with CuKα

radiation, further comprising peaks, in terms of 2 θ

, at about 5.2°

, about 25.6°

, about 17.3°

, about 27.1°

, about 15.8°

, about 20.1°

, about 19.8°

, about 23.1° and

about 15.3°

.

7. The crystalline form according to claim 1 having an X-ray powder diffraction pattern, generated with CuKα

radiation, substantially as shown in FIG. 3.

8. The crystalline form according to claim 1 having a dynamic vapor sorption profile substantially as shown in FIG. 4.

9. The crystalline form according to claim 1 having a purity of 90% or greater.

10. The crystalline form according to claim 1 having a purity of 95% or greater.

11. The crystalline form according to claim 1 having a purity of 99% or greater.

12. The crystalline form according to claim 1 having a purity of 99.5% or greater.

13. A composition comprising the crystalline form according to claim 1 and methanol.

14. A composition comprising the crystalline form according to claim 1 and isopropanol.

15. A composition comprising the crystalline form according to claim 1 and tetrahydrofuran.

16. A composition comprising the crystalline form according to claim 1 and N,N-dimethylacetamide.

17. A composition comprising the crystalline form according to claim 1 and n butanol.

18. A pharmaceutical composition comprising the crystalline form according to claim 1 and a pharmaceutically acceptable carrier.

19. A pharmaceutical composition comprising the crystalline form according to claim 1, methanol, and a pharmaceutically acceptable carrier.

20. A pharmaceutical composition comprising the crystalline form according to claim 1, isopropanol, and a pharmaceutically acceptable carrier.

21. A pharmaceutical composition comprising the crystalline form according to claim 1, tetrahydrofuran, and a pharmaceutically acceptable carrier.

22. A pharmaceutical composition comprising the crystalline form according to claim 1, N,N-dimethylacetamide, and a pharmaceutically acceptable carrier.

23. A pharmaceutical composition comprising the crystalline form according to claim 1, n-butanol, and a pharmaceutically acceptable carrier.

24. A crystalline form of 4-(2-(4-(3-methoxybenzamido)-2-(1 -methyl-i Hpyrazol-5-yl) phenoxy)ethyl)morpholin-4-ium chloride (Form I) having a differential scanning calorimetry thermogram comprising an melting/decomposition endotherm at about 218 °

C.

25. A crystalline form of 4-(2-(4-(3-methoxybenzamido)-2-(i -methyl-i Hpyrazol-5-yl) phenoxy)ethyl)morpholin-4-ium chloride (Form I) having a thermogravimetric analysis profile substantially as shown in FIG. 1.