JPWO2022019998A5 - - Google Patents

Claims (58)

1-[2-[5-[(3-methyl-3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-4-piperidinamine monobenzenesulfonate crystals, comprising: A crystal, wherein the crystal has a powder X-ray diffraction pattern containing peaks at diffraction angles (2Θ±0.2) of 7.1, 14.8, and 18.2. 2. The crystal of claim 1, wherein the powder X-ray diffraction pattern has peaks at diffraction angles (2Θ±0.2) of 7.1, 14.8, 18.2, 24.3, and 26.9. . The powder X-ray diffraction pattern has diffraction angles (2Θ±0.2) of 7.1, 14.8, 16.0, 17.5, 18.2, 24.3, 25.3, and 26.9. The crystal according to claim 1, having a peak at . The powder X-ray diffraction pattern is 7.1, 14.8, 16.0, 16.8, 17.5, 18.2, 19.7, 21.4, 24.3, 25.3, and 26 2. A crystal according to claim 1, having a peak at a diffraction angle of .9 (2Θ±0.2). The powder X-ray diffraction pattern is 7.1, 8.0, 9.6, 11.4, 11.8, 13.9, 14.5, 14.8, 15.5, 16.0, 16. 3, 16.8, 17.5, 18.2, 18.7, 19.3, 19.6, 19.7, 20.0, 20.3, 20.9, 21.4, 21.8, Times of 22.6, 24.3, 25.3, 25.9, 26.9, 28.1, 29.5, 29.9, 31.0, 32.3, 33.4, and 34.3 The crystal according to claim 1, which has a peak at an angle of (2Θ±0.2). 6. The crystal according to claim 1, wherein the crystal is anhydrous. 7. A crystal according to any one of claims 1 to 6, wherein the crystal has a melting point of 264<0>C. 8. Any one of claims 1 to 7, wherein the crystal has an FT-IR spectrum comprising peaks at about 1479, 1271, 1185, 1033, 824, 751, 728, 690, 612, and 564 ^cm . crystal. 9. A crystal according to any one of claims 1 to 8, wherein the crystal is non-hygroscopic. 10. A crystal according to any preceding claim, wherein the crystal has a mass uptake of about 0.9% at 90% RH. 11. A crystal according to any one of claims 1 to 10, wherein the crystal has a birefringent rod-like morphology. 12. A crystal according to any preceding claim, wherein the crystal is substantially pure. 1-[2-[5-[(3-methyl-3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-4-piperidinamine monobenzenesulfonate crystals, comprising: A crystal, wherein the crystal has a powder X-ray diffraction pattern containing peaks at diffraction angles (2Θ±0.2) of 5.3, 18.7, and 23.0. 14. The crystal of claim 13, wherein the powder X-ray diffraction pattern has peaks at diffraction angles (2Θ±0.2) of 5.3, 12.8, 15.5, 18.7, and 23.0. . The powder X-ray diffraction pattern has peaks at diffraction angles (2Θ±0.2) of 5.3, 12.8, 15.2, 15.5, 18.7, 23.0, and 24.2. , the crystal according to claim 13. The powder X-ray diffraction pattern is 5.3, 12.8, 15.2, 15.5, 17.2, 18.7, 20.3, 23.0, 23.5, and 24.2 times. The crystal according to claim 13, which has a peak at an angle of (2Θ±0.2). The powder X-ray diffraction pattern is 3.3, 3.5, 3.8, 5.3, 6.1, 6.4, 8.0, 8.5, 8.8, 8.9, 9. 6, 10.5, 11.1, 11.5, 12.4, 12.8, 13.1, 13.3, 13.7, 14.0, 14.2, 14.5, 15.2, 15.5, 15.9, 16.2, 17.0, 17.2, 17.6, 18.1, 18.7, 19.3, 19.8, 20.3, 20.9, 21. 3, 22.0, 23.0, 23.5, 23.7, 24.2, 25.0, 25.6, 25.8, 26.4, 26.6, 27.4, 28.3, 28.6, 29.1, 29.4, 30.9, 31.5, 31.7, 31.9, 32.0, 32.2, 32.8, 33.8, 34.8, and 39 14. A crystal according to claim 13, having a peak at a diffraction angle of .9 (2Θ±0.2). The crystal according to any one of claims 13 to 17, wherein the crystal is a hemihydrate. 19. A crystal according to any one of claims 13 to 18, wherein the crystal has an onset of melting of about 174<0>C. 20. Any one of claims 13 to 19, wherein the crystal has an FT-IR spectrum comprising peaks at about 1480, 1187, 1124, 1016, 821, 750, 728, 693, 613, and 563 ^cm . crystal. 21. A crystal according to any one of claims 13 to 20, wherein the crystal is slightly hygroscopic. 22. A crystal according to any one of claims 13 to 21, wherein the crystal has a mass uptake of about 1.5% at 90% RH. 23. A crystal according to any one of claims 13 to 22, wherein the crystal has a highly birefringent rod-like morphology. 24. A crystal according to any one of claims 13 to 23, wherein the crystal is substantially pure. 1-[2-[5-[(3-methyl-3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-4-piperidinamine monobenzenesulfonate crystals, comprising: A crystal, wherein the crystal has a powder X-ray diffraction pattern containing peaks at diffraction angles (2Θ±0.2) of 15.8, 19.8, and 21.7. 26. The crystal of claim 25, wherein the powder X-ray diffraction pattern has peaks at diffraction angles (2Θ±0.2) of 12.6, 15.8, 19.8, 20.5, and 21.7. . The powder X-ray diffraction pattern has diffraction angles (2Θ±0.2) of 10.1, 12.6, 15.8, 19.8, 20.5, 21.7, 23.2, and 26.7. 26. The crystal according to claim 25, having a peak at . The powder X-ray diffraction pattern is 7.4, 10.1, 12.6, 15.8, 18.5, 19.8, 20.5, 21.7, 22.8, 23.2, and 26 26. A crystal according to claim 25, having a peak at a diffraction angle of .7 (2Θ±0.2). The powder X-ray diffraction pattern is 2.1, 3.0, 6.3, 7.4, 7.9, 8.7, 10.1, 12.1, 12.6, 13.2, 13. 4, 13.9, 14.9, 15.8, 16.3, 16.5, 16.7, 16.9, 17.3, 17.6, 18.5, 19.1, 19.3, 19.8, 20.5, 20.8, 20.9, 21.7, 22.0, 22.4, 22.8, 22.9, 23.2, 23.8, 24.3, 24. 5, 25.1, 25.9, 26.1, 26.7, 27.0, 27.4, 27.6, 28.2, 28.9, 29.9, 30.1, 30.6, 26. The crystal of claim 25, having peaks at diffraction angles (2Θ±0.2) of 31.0, 31.4, and 31.9. 30. A crystal according to any one of claims 25 to 29, wherein the crystal is anhydrous. 31. A crystal according to any one of claims 25 to 30, wherein the crystal has an onset of melting of about 251<0>C. 32. Any one of claims 25 to 31, wherein the crystal has an FT-IR spectrum comprising peaks at about 1509, 1169, 1015, 954, 821, 799, 749, 728, 613, and 562 ^cm . crystal. 33. A crystal according to any one of claims 25 to 32, wherein the crystal is slightly hygroscopic. 34. A crystal according to any one of claims 25 to 33, wherein the crystal has a mass uptake of about 1.5% at 90% RH. 35. A crystal according to any one of claims 25 to 34, wherein the crystal has a highly birefringent rod-like morphology. 26. The crystal of claim 25, wherein the crystal is substantially pure. 1-[2-[5-[(3-methyl-3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-4-piperidinamine monobenzenesulfonate crystals, comprising: A crystal, wherein the crystal has a powder X-ray diffraction pattern containing peaks at diffraction angles (2Θ±0.2) of 4.8, 22.6, and 23.8. 38. The crystal of claim 37, wherein the powder X-ray diffraction pattern has peaks at diffraction angles (2Θ±0.2) of 4.8, 13.7, 20.6, 22.6, and 23.8. . The powder X-ray diffraction pattern has peaks at diffraction angles (2Θ±0.2) of 4.8, 7.5, 13.7, 18.2, 20.6, 22.6, and 23.8. , the crystal according to claim 37. The powder X-ray diffraction pattern is 4.8, 7.5, 13.7, 18.2, 18.4, 18.9, 20.0, 20.6, 22.6, and 23.8 times. 38. The crystal according to claim 37, which has a peak at an angle of (2Θ±0.2). The powder X-ray diffraction pattern is 4.8, 6.3, 7.5, 9.3, 11.6, 13.4, 13.7, 14.5, 15.2, 15.4, 15. 6, 16.7, 17.3, 17.8, 18.2, 18.4, 18.9, 19.4, 20.0, 20.2, 20.6, 20.9, 21.3, 22.6, 22.9, 23.8, 24.4, 24.8, 25.3, 26.2, 27.4, 27.8, 28.1, 28.3, 28.4, 28. 38. Having peaks at diffraction angles (2Θ±0.2) of 9, 29.3, 29.8, 31.0, 32.1, 32.6, 33.3, and 34.2. crystal. 42. The crystal according to any one of claims 37 to 41, wherein the crystal is a solvate. 43. A crystal according to any one of claims 37 to 42, wherein the solvate is a N,N'-dimethylacetamide solvate. 44. A crystal according to any one of claims 37 to 43, wherein the solvate is an acetonitrile, butyl acetate, or ethanol solvate. 45. The crystal of any one of claims 37-44, wherein the crystal has an onset of decomposition of about 241<0>C. 46. The crystal has an FT-IR spectrum comprising peaks at about 1479, 1272, 1184, 1033, 824, 751, 728, 690, 612, and 564 ^cm . crystal. 47. A crystal according to any one of claims 37 to 46, wherein the crystal is hygroscopic. 48. A crystal according to any one of claims 37 to 47, wherein the crystal has a mass uptake of 1.5% at 0% to 10% RH. 49. A crystal according to any one of claims 37 to 48, wherein the crystal has no defined morphology and has low birefringence. 38. The crystal of claim 37, wherein the crystal is substantially pure. 1-[2-[5-[(3-methyl-3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-4-piperidinamine monobenzenesulfonate solid, A solid that is amorphous. 52. A pharmaceutical composition comprising a crystal according to any one of claims 1 to 51 and a pharmaceutically acceptable carrier. A medicament for treating a subject suffering from a proliferative disease, comprising a crystal according to any one of claims 1 to 51. The proliferative disease is Hodgkin's disease, myeloma, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia. (CML), chronic neutrophilic leukemia (CNL), acute undifferentiated leukemia (AUL), anaplastic large cell lymphoma (ALCL), prolymphocytic leukemia (PML), juvenile myelomonocytic leukemia (JMML) ), adult T-cell ALL, AML with three-cell myelodysplasia (AMLITMDS), mixed leukemia (MLL), myelodysplastic syndrome (MDS), myeloproliferative disorder (MPD), multiple myeloma, biliary tract Cancer, Bladder Cancer, Breast Cancer, Cervical Cancer, CNS Cancer, Colon Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer, Esophagogastric Junction (GEJ) Adenocarcinoma, Gastric Adenocarcinoma, Stage IIIB Gastric Adenocarcinoma, Stage IV Invasive Gastric Adenocarcinoma , metastatic esophageal adenocarcinoma, glioblastoma, head and neck cancer, hepatocellular carcinoma, liver cancer, lung cancer, melanoma, non-small cell carcinoma, nasopharyngeal cancer, neuroendocrine cancer, ovarian cancer, pancreatic cancer, prostate cancer, 54. The agent according to claim 53, selected from renal cancer, salivary gland cancer, small cell lung cancer, squamous cell carcinoma, skin cancer, testicular cancer, thyroid cancer, thymoma, uterine cancer, or other tumors. 1-[2-[5-[(3-methyl-3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-4-piperidinamine Monobenzenesulfonate to 1,1-dimethoxymethane or suspending in 1-butanol followed by stirring or shaking until precipitation. 1-[2-[5-[(3-methyl-3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-4-piperidinamine monobenzenesulfonate in 98.5% ethanol/ 14. A method of preparing crystals according to claim 13, comprising suspending in 1.5% water (% v/v) followed by shaking until precipitation. 1-[2-[5-[(3-methyl-3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-4-piperidinamine Monobenzenesulfonate 99% Ethanol/1% 26. A method of preparing crystals according to claim 25, comprising suspending in toluene (% v/v) followed by shaking until precipitation. 1-[2-[5-[(3-methyl-3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-4-piperidinamine Monobenzenesulfonate to N,N'-dimethyl 38. A method of preparing crystals according to claim 37, comprising suspending in acetamide, acetonitrile, butyl acetate, or ethanol, followed by shaking until precipitation.