Polymorphs of syk inhibitors

Patent metadata

Field	Value
Publication number	US-2020277293-A1
Application number	US-201816641331-A
Country	US
Kind code	A1
Filing date	Aug 10, 2018
Priority date	Aug 25, 2017
Publication date	Sep 3, 2020
Grant date	—

Abstract

Polymorphs of a bis-mesylate salt of a compound of Formula I:

are provided.

First claim

What is claimed is:

1 . Polymorphic Form I of a hydrate of a bis-mesylate salt of compound of Formula I:

2 . The polymorphic Form I of claim 1 characterized by an X-ray diffraction pattern comprising 2θ-reflections, ±0.2 degrees 2θ, at 6.6, 17.1, and 21.3.

3 . The polymorph Form I of claim 2 , characterized by X-ray diffraction pattern with one or more additional 2θ-reflections, ±0.2 degrees 2θ, at 14.1, 14.8, 16.0, 22.2 or 24.3.

4 . The polymorph Form I of any of claims 1 - 3 , characterized by an X-ray diffraction pattern substantially as shown in FIG. 1A .

5 . The polymorph Form I of any of claims 1 - 4 having differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 1B .

6 . The polymorph Form I of any of claims 1 - 5 having thermogravimetric analysis (TGA) substantially as shown in FIG. 1C .

7 . Polymorphic Form II of a hydrate of a bis-mesylate salt of compound of Formula I:

8 . The polymorphic Form II of claim 7 characterized by an X-ray diffraction pattern comprising 2θ-reflections, ±0.2 degrees 2θ, at 14.8, 17.4 and 20.1.

9 . The polymorph Form II of any of claims 7 - 8 , characterized by X-ray diffraction pattern with one or more additional 2θ-reflections, ±0.2 degrees 2θ, at 5.9, 7.9, 13.6, 20.6 or 26.5.

10 . The polymorph Form II of any of claims 7 - 9 , characterized by an X-ray diffraction pattern substantially as shown in FIG. 2A .

11 . The polymorph Form II of any of claims 7 - 10 having differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 2B .

12 . The polymorph Form II of any of claims 7 - 11 having thermogravimetric analysis (TGA) substantially as shown in FIG. 2C .

13 . Polymorphic Form XIII of a hydrate of a bis-mesylate salt of compound of Formula I:

14 . The polymorphic Form XIII of claim 13 characterized by an X-ray diffraction pattern comprising 2θ-reflections, ±0.2 degrees 2θ, at 11.6, 17.4 and 19.5.

15 . The polymorph Form XIII of any of claims 13 - 14 , characterized by X-ray diffraction pattern with one or more additional 2θ reflections, ±0.2 degrees 2θ, at 21.8, 26.8, 21.3 or 15.4.

16 . The polymorph Form XIII of any of claims 13 - 15 , characterized by an X-ray diffraction pattern substantially as shown in FIG. 3A .

17 . The polymorph Form XIII of any of claims 13 - 16 having differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 3B .

18 . The polymorph Form XIII of any of claims 13 - 17 having thermogravimetric analysis (TGA) substantially as shown in FIG. 3C .

19 . Polymorphic Form XIV of a bis-mesylate salt of compound of Formula I:

20 . The polymorphic Form XIV of claim 19 characterized by an X-ray diffraction pattern comprising 2θ-reflections, ±0.2 degrees 2θ, at 15.0, 16.1 and 22.9.

21 . The polymorph Form XIV of any of claims 19 - 20 , characterized by X-ray diffraction pattern with one or more additional 2θ reflections, ±0.2 degrees 2θ, at 6.5, 18.7, 24.2, 25.4 or 26.4.

22 . The polymorph Form XIV of any of claims 19 - 21 , characterized by an X-ray diffraction pattern substantially as shown in FIG. 4A .

23 . The polymorph Form XIV of any of claims 19 - 22 having differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 4B .

24 . The polymorph Form XIV of any of claims 19 - 23 having thermogravimetric analysis (TGA) substantially as shown in FIG. 4C .

25 . Polymorphic Form XV of a hydrate of a bis-mesylate salt of compound of Formula I:

26 . The polymorphic Form XV of claim 25 characterized by an X-ray diffraction pattern comprising 2θ-reflections, ±0.2 degrees 2θ, at 20.6, 22.0 and 25.7.

27 . The polymorph Form XV of any of claims 25 - 26 , characterized by X-ray diffraction pattern with one or more additional 2θ reflections, ±0.2 degrees 2θ, at 7.0, 13.2, 15.3, 19.6 or 26.7.

28 . The polymorph Form XV of any of claims claim 25 - 27 , characterized by an X-ray diffraction pattern substantially as shown in FIG. 5A .

29 . The polymorph Form XV of any of claims 25 - 28 having differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 5B .

30 . The polymorph Form XV of any of claims 25 - 29 having thermogravimetric analysis (TGA) substantially as shown in FIG. 5C .

31 . Polymorphic Form XVI of a hydrate of a bis-mesylate salt of compound of Formula I:

32 . The polymorphic Form XVI of claim 36 characterized by an X-ray diffraction pattern comprising 2θ-reflections, ±0.2 degrees 2θ, at 7.8, 19.8 and 22.2.

33 . The polymorph Form XVI of any of claims 31 - 32 , characterized by X-ray diffraction pattern with one or more additional 2θ reflections, ±0.2 degrees 2θ, at 5.0, 14.8, 17.3, 17.8 or 26.0.

34 . The polymorph Form XVI of claim of any of claims 31 - 33 , characterized by an X-ray diffraction pattern substantially as shown in FIG. 6A .

35 . The polymorph Form XVI of any of claims 31 - 34 having differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 6B .

36 . The polymorph Form XVI of any of claims 31 - 35 having thermogravimetric analysis (TGA) substantially as shown in FIG. 6C .

37 . Polymorphic Form XVIII of a hydrate of a bis-mesylate salt of compound of Formula I:

38 . The polymorphic Form XVIII of claim 37 characterized by an X-ray diffraction pattern comprising 2θ-reflections, ±0.2 degrees 2θ, at 4.5, 8.9 and 22.1.

39 . The polymorph Form XVIII of any of claims 37 - 38 , characterized by X-ray diffraction pattern with one or more additional 2θ reflections, ±0.2 degrees 2θ, at 13.3, 18.0, 24.7, 27.2 or 31.6.

40 . The polymorph Form XVIII of any of claims 37 - 39 , characterized by an X-ray diffraction pattern substantially as shown in FIG. 7A .

41 . The polymorph Form XVIII of any of claims 37 - 40 having differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 7B .

42 . The polymorph Form XVIII of any of claims 37 - 41 having thermogravimetric analysis (TGA) substantially as shown in FIG. 7C .

43 . Polymorphic Form VI of a formic acid solvate of a bis-mesylate salt of compound of Formula I:

44 . The polymorphic Form VI of claim 43 characterized by an X-ray diffraction pattern comprising 2θ-refle

Assignees

• Gilead Sciences Inc

Inventors

• Elford Tim G
• Fung Peter Chee-Chu
• Hartmeier Paul Robert
• Jernelius Jesper Alexis
• Morrison Henry

Classifications

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/02

  specific for leukemia · CPC title