Process for preparing (5S)-{[2-(4-carboxyphenyl)ethyl] |2-(2-{|3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]aminol-5,6,7,8-tetrahydroquinoline-2-carboxylic acid and its crystalline forms for use as pharmaceutically active compound

Patent metadata

Field	Value
Publication number	US-12202805-B2
Application number	US-202318506737-A
Country	US
Kind code	B2
Filing date	Nov 10, 2023
Priority date	Dec 29, 2021
Publication date	Jan 21, 2025
Grant date	Jan 21, 2025

Abstract

The present invention relates to a novel and improved process for preparing (5S)-{[2-(4-carboxyphenyl)ethyl][2-(2-{[3-chloro-4′-(trifluo-romethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylic acid of the formula (I) and to novel crystalline forms of it, which is i.a. the pseudopolymorphic form monohydrate I (I-M-I) or the pseudopolymorphic form monohydrate II (I-M-II), furthermore the present invention relates to a novel and selective crystallization process for preparation of the pseudopolymorphic form monohydrate I (I-M-I) or the pseudopolymorphic form monohydrate II (I-M-II), preferably monohydrate I of formula (I-M-I) and to pharmaceutical compositions comprising monohydrate I of formula (I-M-I) and to its use for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of pulmonary and cardiopulmonary and cardiovascular diseases.

First claim

The invention claimed is:

1. A crystalline monohydrate form of Compound 1:

2. The crystalline monohydrate form of claim 1 , having X-ray powder diffraction reflections at 12.8±0.2 and 29.2±0.2, using Cu K alpha radiation when measured at 25° C.

3. The crystalline monohydrate form of claim 2 , having at least one additional reflection at 6.9±0.2 or 7.2±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

4. The crystalline monohydrate form of claim 2 , having at least one additional reflection at 6.9±0.2 or 7.3±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

5. The crystalline monohydrate form of claim 2 , having at least one additional reflection at 6.9±0.2, 7.2±0.2, 7.3±0.2, 15.2±0.2, or 23.0±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

6. The crystalline monohydrate form of claim 1 , having X-ray powder diffraction reflections at 12.8±0.2, 16.0±0.2, and 25.8±0.2, using Cu K alpha radiation when measured at 25° C.

7. The crystalline monohydrate form of claim 6 , having at least one additional reflection at 6.9±0.2 or 7.2±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

8. The crystalline monohydrate form of claim 6 , having at least one additional reflection at 6.9±0.2 or 7.3±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

9. The crystalline monohydrate form of claim 6 , having at least one additional reflection at 6.9±0.2, 7.2±0.2, 7.3±0.2, or 15.2±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

10. The crystalline monohydrate form of claim 1 , having X-ray powder diffraction reflections at 12.8±0.2, 20.5±0.2, and 25.8±0.2, using Cu K alpha radiation when measured at 25° C.

11. The crystalline monohydrate form of claim 10 , having at least one additional reflection at 6.9±0.2 or 7.2±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

12. The crystalline monohydrate form of claim 10 , having at least one additional reflection at 6.9±0.2 or 7.3±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

13. The crystalline monohydrate form of claim 10 , having at least one additional reflection at 6.9±0.2, 7.2±0.2, 7.3±0.2, 15.2±0.2, or 25.1±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

14. The crystalline monohydrate form of claim 1 , having at least three X-ray powder reflections selected from 5.7±0.2, 6.9±0.2, 7.2±0.2, 7.3±0.2, 9.9±0.2, 10.4±0.2, 10.6±0.2, 11.1±0.2, 11.5±0.2, 12.0±0.2, 12.3±0.2, 12.4±0.2, 12.8±0.2, 13.7±0.2, 14.1±0.2, 14.3±0.2, 15.2±0.2, 15.6±0.2, 16.0±0.2, 16.9±0.2, 17.2±0.2, 17.5±0.2, 17.7±0.2, 18.0±0.2, 18.4±0.2, 18.8±0.2, 19.2±0.2, 19.9±0.2, 20.2±0.2, 20.5±0.2, 20.7±0.2, 21.3±0.2, 21.9±0.2, 22.2±0.2, 22.5±0.2, 23.0±0.2, 23.4±0.2, 23.7±0.2, 24.1±0.2, 25.1±0.2, 25.8±0.2, 26.0±0.2, 26.4±0.2, 28.9±0.2, 29.2±0.2, 29.4±0.2, 30.6±0.2, 31.1±0.2, 32.2±0.2, and 35.3±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

15. The crystalline monohydrate form of claim 2 , not having a reflection at 3.1±0.2 or 9.3±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

16. The crystalline monohydrate form of claim 6 , not having a reflection at 3.1±0.2 or 9.3±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

17. The crystalline monohydrate form of claim 10 , not having a reflection at 3.1±0.2 or 9.3±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

18. The crystalline monohydrate form of claim 14 , not having a reflection at 3.1±0.2 or 9.3±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

19. The crystalline monohydrate form of claim 2 , not having a reflection at 6.1±0.2 or 8.5±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

20. The crystalline monohydrate form of claim 6 , not having a reflection at 6.1±0.2 or 8.5±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

21. The crystalline monohydrate form of claim 10 , not having a reflection at 6.1±0.2 or 8.5±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

22. The crystalline monohydrate form of claim 14 , not having a reflection at 6.1±0.2 or 8.5±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

23. The crystalline monohydrate form of claim 6 , not having a reflection at one of 3.1 0.2, 6.1±0.2, 7.6±0.2, 7.9±0.2, 8.5±0.2, 9.3±0.2, 14.8±0.2, 30.0±0.2, or 31.6±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

24. The crystalline monohydrate form of claim 6 , not having a reflection at one of 3.1 0.2, 6.1±0.2, 7.6±0.2, 7.9±0.2, 8.5±0.2, 9.3±0.2, 14.8±0.2, 30.0±0.2, or 31.6±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

25. The crystalline monohydrate form of claim 10 , not having a reflection at one of 3.1 0.2, 6.1±0.2, 7.6±0.2, 7.9±0.2, 8.5±0.2, 9.3±0.2, 14.8±0.2, 30.0±0.2, or 31.6±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

26. The crystalline monohydrate form of claim 14 , not having a reflection at one of 3.1 0.2, 6.1±0.2, 7.6±0.2, 7.9±0.2, 8.5±0.2, 9.3±0.2, 14.8±0.2, 30.0±0.2, or 31.6±0.2°2θ, using Cu K alpha radiation when measured at 25° C.

27. The crystalline monohydrate form of claim 1 , having a Raman spectrum with at least the following band maxima: 3073, 2950, 2937, 1685, 1616, 1527, 1293, 1278, and 1259 cm −1 .

Assignees

• Bayer Ag
• Bayer Pharma AG

Inventors

• Olenik Britta
• Keil Birgit
• Rösler Bernd
• Fey Peter
• Schirmer Heiko
• Becker Guido
• Egger Julian
• Bothe Clemens
• Faber Helene

Classifications

• A61K9/0075

  for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P11/08

  Bronchodilators · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title