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

Patent metadata

Field	Value
Publication number	US-10793554-B2
Application number	US-201916667602-A
Country	US
Kind code	B2
Filing date	Oct 29, 2019
Priority date	Oct 29, 2018
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

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 the free base of (4-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl)benzoyl)piperazin-1-yl)(1-hydroxycyclopropyl)methanone designated the Form B solid form that exhibits a X-ray powder diffraction pattern (XRPD) (a) having characteristic peaks expressed in degrees 2-theta (±0.2 degrees 2-theta) at 9.6, 10.1, 15.4, 19.6, and 22.3 and (b) characterized by the absence of a characteristic peak expressed in degrees 2-theta (±0.2 degrees 2-theta) at 24.2.

2. The solid form of claim 1 , wherein the solid form is characterized by a differential scanning calorimetry (DSC) thermogram having one endotherm at 225.7° C., when the DSC is performed at 10° C./min from about 20° C. to about 350° C. using dry nitrogen to purge the system.

3. The solid form of claim 1 , wherein the solid form is characterized by the X-ray powder diffraction pattern shown in FIG. 3 .

4. The solid form of claim 1 , wherein the solid form is free of the Form C solid form of (4-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl) benzoyl)piperazin-1-yl)(1-hydroxycyclopropyl)methanone.

5. The solid form of claim 1 , wherein the solid form is free of the Form X solid form of (4-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl)benzoyl) piperazin-1-yl)(1-hydroxycyclopropyl)methanone.

6. The solid form of claim 1 , wherein the solid form is characterized by a mass change of less than about 0.5 wt % from 0% RH to 95% RH at 25 degrees C. by dynamic vapor sorption (DVS), when the DVS is performed according to Table 4

TABLE 4

Parameters
Values

Temperature
25° C.

Sample size
10-20 mg

Gas and flow rate
N 2 , 200 mL/min

dm/dt
0.002%/min

Min. dm/dt stability duration
10 min

Max. equilibrium time
360 min

Relative humidity (RH) range
20% RH-95% RH-0% RH-95% RH

Relative humidity (RH) step size
10%.

7. The solid form of claim 1 , wherein the solid form is characterized by a thermogravimetric analysis (TGA) weight loss of less than about 0.5% up to 100 degrees C., when the TGA is performed from 20-350 degrees C., at a ramp rate of 10 degrees C./min. and using dry nitrogen to purge the system.

8. The solid form of claim 1 , wherein the solid form is characterized by a single endothermic peak onset temperature of about 223.9 degrees C. by differential scanning calorimetry (DSC) thermogram before decomposition, when the DSC is performed at 10° C./min from about 20° C. to about 350° C. using dry nitrogen to purge the system.

9. The solid form of claim 1 , wherein the solid form exhibits an X-ray powder diffraction pattern (XRPD) having peaks expressed in degrees 2-theta at approximately:

9.6
17.4
25.0

10.1
18.2
25.3

10.7
18.5
26.5

12.6
19.6
26.9

13.9
20.2
28.0

14.3
22.1

15.4
22.3
29.0

16.4
23.4
29.5

16.6
23.8
30.5

31.1
32.9
37.3

31.8
34.1
37.9.

10. The solid form of claim 1 , wherein the solid form is characterized by an X-ray powder diffraction pattern (XRPD) having one or more peaks at substantially the same angles (2 theta±0.2), corresponding to d-spacing (angstroms±0.2) of:

2 Theta
d-spacing (Å)

9.6
9.2

10.1
8.7

10.7
8.3

12.6
7.0

13.9
6.4

14.3
6.2

15.4
5.7

16.4
5.4

16.6
5.3

17.4
5.1

18.2
4.9

18.5
4.8

19.6
4.5

20.2
4.4

22.1
4.0

22.3
4.0

23.4
3.8

23.8
3.7

25.0
3.6

25.3
3.5

26.5
3.4

Assignees

• Forma Therapeutics Inc

Inventors

• Luke George P
• Hubbs Stephen
• Martin Matthew W
• 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