HDAC inhibitor solid state forms
The present disclosure relates to the crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide and methods of making the same. The crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide is useful in preparation of pharmaceutical compositions and dosage forms for the treatment of cancer, immune disorders and inflammation.
1. Crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide, characterized by at least three X-ray diffraction pattern reflections selected from a 2 theta value of 3.7°±0.3, 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 30.1°±0.3.
2. Crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide, characterized by at least five X-ray diffraction pattern reflections selected from a 2 theta value of 3.7°±0.3, 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 30.1°±0.3.
3. Crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide, characterized by the X-ray powder diffraction pattern as shown in FIG. 1 .
4. Crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide, characterized by:
(i) at least two X-ray diffraction pattern reflections selected from a 2 theta value of 3.7°±0.3, 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 30.1°±0.3; and
(ii) differential scanning calorimetry (DSC), wherein the DSC thermogram exhibits a single exothermic event with an onset temperature at about 222.1° C.±5.0 (433 J/g) or an exothermic peak at 225.8° C.±5.0.
5. The crystalline mesylate of claim 1 , wherein the amount of another crystalline form is 5% (w/w) or less.
6. The crystalline mesylate of claim 1 , wherein the amount of impurities is 3% or less.
7. The crystalline mesylate of claim 1 , wherein the amount of an amorphous form is 5% (w/w) or less.
8. The crystalline mesylate of claim 2 , wherein the amount of another crystalline form is 5% (w/w) or less.
9. The crystalline mesylate of claim 2 , wherein the amount of an amorphous form is 5% (w/w) or less.
10. The crystalline mesylate of claim 2 , wherein the amount of impurities is 3% or less.
11. The crystalline mesylate of claim 3 , wherein the amount of another crystalline form is 5% (w/w) or less.
12. The crystalline mesylate of claim 3 , wherein the amount of an amorphous form is 5% (w/w) or less.
13. The crystalline mesylate of claim 3 , wherein the amount of impurities is 3% or less.
14. The crystalline mesylate of claim 4 , wherein the amount of another crystalline form is 5% (w/w) or less.
15. The crystalline mesylate of claim 4 , wherein the amount of an amorphous form is 5% (w/w) or less.
16. The crystalline mesylate of claim 4 , wherein the amount of impurities is 3% or less.
17. Crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide, characterized by at least five X-ray diffraction pattern reflections selected from a 2 theta value of 3.7°±0.3, 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, 30.1°±0.3, 23.4°±0.3, 16.7°±0.3, or 18.7°±0.3.
18. The crystalline mesylate of claim 17 , wherein the amount of another crystalline form is 5% (w/w) or less.
19. The crystalline mesylate of claim 17 , wherein the amount of an amorphous form is 5% (w/w) or less.
20. The crystalline mesylate of claim 17 , wherein the amount of impurities is 3% or less.