Solid forms of (4-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl)benzoyl) piperazine-1-yl)(1-hydroxycyclopropyl)methanone

Patent metadata

Field	Value
Publication number	US-11267805-B2
Application number	US-202017006317-A
Country	US
Kind code	B2
Filing date	Aug 28, 2020
Priority date	Oct 29, 2018
Publication date	Mar 8, 2022
Grant date	Mar 8, 2022

Abstract

The present disclosure reports solid forms of (4-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl)benzoyl)piperazin-1-yl)(1-hydroxycyclopropyl)methanone:

First claim

What is claimed is:

1. A solid form of Compound 1 free base:

wherein the solid form is selected from the group consisting of:
Mixture A, characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 10.1, 15.4, 19.6, 21.0, and 22.3;
Form B, characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 10.1, 15.4, 19.6, and 22.3;
Form C, characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 15.4, 19.6, 22.3, and 26.6; and
Form X, characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 7.2, 8.5, 14.9, 16.1, and 17.8; and
Form Z, characterized by an XRPD pattern having diffractions at angles (2 theta) as exemplified in FIG. 11 .

2. The solid form of claim 1 , wherein the solid form is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 10.1, 15.4, 19.6, and 22.3.

3. The solid form of claim 1 , wherein the solid form is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 15.4, 19.6, and 22.3 and not having a diffraction at angle (2 theta±0.2) of 24.2.

4. The solid form of claim 1 , wherein the solid form is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 10.1, 12.6, 13.9, 15.4, 16.4, 19.6, 20.2, 22.3, 23.4, 23.8, and 25.3.

5. The solid form of claim 3 , wherein the solid form is Form B and is characterized by a DSC endotherm having an endotherm at about 226° C.

6. The solid form of claim 3 , wherein the solid form is Form B and is characterized by a TGA with a weight loss of about 0.5% between 21° C. and 100° C.

7. The solid form of claim 3 , wherein the solid form is Form B and is characterized by a DVS of about 0.5% water by weight below 95% relative humidity.

8. The solid form of claim 1 , wherein the solid form is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 15.4, 19.6, 22.3, and 26.6.

9. The solid form of claim 1 , wherein the solid form is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 15.4, 19.6, 22.3, 24.2, and 26.6.

10. The solid form of claim 1 , wherein the solid form is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 7.2, 8.5, 14.9, 16.1, and 17.8.

11. A composition comprising Compound 1 free base Mixture A:

wherein Mixture A is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 10.1, 15.4, 19.6, and 22.3.

12. The composition of claim 11 , wherein Mixture A is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 10.1, 15.4, 19.6, 21.0, and 22.3.

13. A pharmaceutical composition comprising a solid form of Compound 1 free base:

and a pharmaceutically acceptable carrier, wherein the solid form of Compound 1 is Form B and is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 10.1, 15.4, 19.6, and 22.3.

14. The pharmaceutical composition of claim 13 , wherein the solid form is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 10.1, 15.4, 19.6, and 22.3 and not having a diffraction at angle (2 theta±0.2) of 24.2.

15. The pharmaceutical composition of claim 13 , wherein the solid form is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 15.4, 19.6, and 22.3 and not having a diffraction at angle (2 theta±0.2) of 24.2.

16. The pharmaceutical composition of claim 13 , wherein the solid form is characterized by an XRPD pattern having diffractions at angles (2 theta±0.2) of 9.6, 10.1, 12.6, 13.9, 15.4, 16.4, 19.6, 20.2, 22.3, 23.4, 23.8, and 25.3.

17. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition is substantially free of Solid Form X.

18. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition is substantially free of Solid Forms C, X, and Z.

19. A solid form of Compound 1:

wherein the solid form is the form that would be obtained by a process comprising:
suspending at least one of Mixture A, Form C, and Form X of Compound 1 in a solvent selected from a group consisting of ethyl acetate (EtOAc), acetonitrile (ACN), heptane, isopropyl alcohol (IPA), and ethanol (EtOH) to provide a slurry; and
maintaining the slurry for a period of at least 5 hours to afford the solid form of Compound 1.

20. The solid form of claim 19 , wherein the slurry is heated to a temperature from about 50° C. to about 100° C. after suspension in the solvent.

21. The solid form of claim 19 , further comprising isolating the solid form of Compound 1 from the slurry.

Assignees

• Forma Therapeutics Inc

Inventors

• Luke George P
• Hubbs Stephen
• Martin Matthew W
• Schiller Shawn E R
• Wenslow Robert
• Shi Yawei
• Huang Jun

Classifications

• C07D295/104

  with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D403/10 Primary

  linked by a carbon chain containing aromatic rings · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title