RU2020143044A - SALT FORM - Google Patents

Claims (23)

1. Ditosylate salt of a compound of formula I:

(I). 2. Ditosylate salt of the compound of formula I according to claim 1 in crystalline form. 3. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1 and 2 in crystalline form A. 4. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1-3, characterized by a powder XRD pattern containing two or more peaks selected from 7.2 ± 0.2 degrees two-theta, 8.5 ± 0.2 degrees two-theta, 10.4 ± 0.2 degrees two -theta, 12.3±0.2 degrees two-theta, 14.5±0.2 degrees two-theta, 16.1±0.2 degrees two-theta, 18.3±0.2 degrees two-theta , 20.1±0.2 degrees two-theta and 21.1±0.2 degrees two-theta. 5. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1-4, characterized by a powder XRD pattern with peaks at approximately 7.2 ± 0.2 degrees two-theta and 10.4 ± 0.2 degrees two-theta. 6. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1-5, characterized by a powder XRD pattern with peaks at approximately 7.2 ± 0.2 degrees two-theta, 8.5 ± 0.2 degrees two-theta, 10.4 ± 0.2 degrees two-theta, 18, 3±0.2 degrees two-theta, 20.1±0.2 degrees two-theta, and 21.1±0.2 degrees two-theta. 7. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1-6, characterized by a powder XRD pattern with peaks at approximately 7.2 ± 0.2 degrees two-theta, 8.5 ± 0.2 degrees two-theta, 10.4 ± 0.2 degrees two-theta, 12, 3±0.2 degrees two-theta, 14.5±0.2 degrees two-theta, 16.1±0.2 degrees two-theta, 18.3±0.2 degrees two-theta, 20.1± 0.2 degrees two-theta and 21.1±0.2 degrees two-theta. 8. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1-7, characterized by a powder XRD pattern essentially depicted in FIG. one. 9. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1-8, characterized by a DSC thermogram having an endotherm with an onset at about 222 to 228°C and a maximum at about 226 to 230°C. 10. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1-9, characterized by a DSC thermogram essentially depicted in FIG. 2. 11. A pharmaceutical composition containing a ditosylate salt of a compound of formula I according to any one of paragraphs. 1-10 and a pharmaceutically acceptable excipient. 12. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1-11 for use in therapy. 13. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1-12 for use in the treatment of a proliferative disorder. 14. Ditosylate salt of the compounds of formula I according to any one of paragraphs. 1-13 for use in the treatment of cancer. 15. A ditosylate salt of a compound of formula I for use according to claim 14 wherein the cancer is selected from breast cancer, lung cancer, ovarian cancer, cervical cancer, pancreatic cancer, bladder cancer, esophageal cancer and skin cancer. 16. A method for preparing the ditosylate salt of a compound of formula I according to claim 1, comprising preparing a mixture of p-toluenesulfonic acid and a compound of formula I in an organic solvent and water, where the organic solvent is selected from acetone, 2-butanone and 2-propanol. 17. The method according to p. 16, including: (a') suspending the compound of formula I in a solution containing 2-propanol; (b') heating the product of step (a') to a temperature of about 60 to 75°C; (c') mixing the product of step (b') with an aqueous solution of p-toluenesulfonic acid; and (d') cooling the product of step (c') to a temperature of about 0 to 40°C to obtain the ditosylate salt of the compound of formula I. 18. The process of claim 17, wherein the ratio of 2-propanol to water in step (c') is from about 9:1 to about 13:1.