Granted Patent B2

US 12,286,431 · App. 18/025,817 · Granted Apr 29, 2025

Inventors: Patricia Andres (San Diego, CA); Samuel Andrew (Cambridge, GB); Cheng Yi Chen (San Diego, CA); Susana Del Rio Gancedo (Cambridge, GB); Tawfik Gharbaoui (Escondido, CA); Jennifer Nelson (West Lafayette, IN)

Assignee: MIRATI THERAPEUTICS, INC.

C07D471/04A61P35/00C07B2200/13

Abstract

Claims (19)

1. A crystalline form of 2-[(2S)-4-[7-(8-chloro-1-naphthyl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl]acetonitrile, wherein the crystalline form is Crystalline Form D, having an X-ray powder diffraction pattern comprising a peak at °2θ at 4.4±0.2.

2. The crystalline form according to claim 1 , having an X-ray powder diffraction pattern comprising two or more peaks at °2θ selected from 4.4±0.2, 13.6±0.2, 13.8±0.2, 15.2±0.2, 16.3±0.2, 17.7±0.2, 18.0±0.2, 20.9±0.2, 22.6±0.2, 23.0±0.2, and 27.6±0.2.

3. The crystalline form according to claim 1 , having an X-ray powder diffraction pattern comprising peaks at °2θ at 4.4±0.2, 13.6±0.2, 13.8±0.2, 15.2±0.2, 16.3±0.2, 17.7±0.2, 18.0±0.2, 20.9±0.2, 22.6±0.2, 23.0±0.2, and 27.6±0.2.

4. The crystalline form according to claim 1 , having an XRPD pattern as shown in FIG. 13 .

5. The crystalline form according to claim 1 , having a DSC thermogram as shown in FIG. 14 .

6. The crystalline form according to claim 1 , having a TGA profile as shown in FIG. 14 .

7. The crystalline form according to claim 1 , wherein the crystalline form is a hydrate.

8. The crystalline form according to claim 1 , wherein the crystalline form comprises less than 1.0% by weight of residual organic solvents.

9. A pharmaceutical composition comprising the crystalline form of claim 1 and at least one pharmaceutically acceptable excipient and/or diluent.

10. A crystalline form of 2-[(2S)-4-[7-(8-chloro-1-naphthyl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl]acetonitrile, wherein the crystalline form is Crystalline Form E, having an X-ray powder diffraction pattern comprising at least one peak at °2θ selected from 5.2±0.2 and 10.2±0.2.

11. The crystalline form according to claim 10 , wherein the crystalline form is the Crystalline Form E having an X-ray powder diffraction pattern comprising peaks at °2θ at 5.2±0.2 and 10.2±0.2.

12. The crystalline form of claim 10 , having an X-ray powder diffraction pattern comprising two or more peaks at °2θ selected from 5.2±0.2, 10.2±0.2, 11.8±0.2, 13.5±0.2, 14.3±0.2, 16.9±0.2, 17.7±0.2, 20.3±0.2, 20.5±0.2 and 21.9±0.2.

13. The crystalline form of claim 10 , having an X-ray powder diffraction pattern comprising peaks at °2θ at 5.2±0.2, 10.2±0.2, 11.8±0.2, 13.5±0.2, 14.3±0.2, 16.9±0.2, 17.7±0.2, 20.3±0.2, 20.5±0.2 and 21.9±0.2.

14. The crystalline form according to claim 10 , having an XRPD pattern as shown in FIG. 15 .

15. The crystalline form according to claim 10 , having a DSC thermogram as shown in FIG. 16 .

16. The crystalline form according to claim 10 , having a TGA profile shown in FIG. 17 .

17. The crystalline form according to claim 10 , having a DVS isotherm as shown in FIG. 18 .

18. The crystalline form according to claim 10 , wherein the crystalline form comprises less than 1.0% by weight of residual organic solvents.

19. A pharmaceutical composition comprising the crystalline form of claim 10 and at least one pharmaceutically acceptable excipient and/or diluent.

Continuity (3)

References Cited (392)