Method for preparing a non-hydratable crystal form
View Patent ↗A method is disclosed for preparing a non-hydratable crystal form from a hydratable crystal form of 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)-carbonyl]phenyl]-1H-pyrazole-5-carboxamide (Compound 1).
1. A method for preparing Polymorph A of 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide characterized by a X-ray diffraction pattern having at least the 2θ reflection positions
2θ
6.78
11.09
19.94
20.99
26.57
26.98
31.52
comprising heating at a temperature between about 40° C. and the boiling point of the solvent a mixture comprising a solvent selected from the group consisting of water, n-heptane, 1-chlorobutane, toluene, 1-butanol and 1-pentanol, and Polymorph B of 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide characterized by a X-ray diffraction pattern having at least the 2θ reflection positions
2θ
7.43
9.89
18.68
19.36
22.16
23.09
25.70.
2. The method of claim 1 wherein the solvent is n-heptane.
3. The method of claim 1 wherein the solvent is toluene.
4. The method of claim 1 wherein the solvent is 1-chlorobutane.
5. The method of claim 1 wherein the solvent is 1-butanol or 1-pentanol.
6. The method of claim 1 wherein the solvent is water.
7. The method of claim 6 wherein the temperature is between about 60 and about 100° C.
8. The method of claim 7 wherein the temperature is between about 70 and about 100° C.
9. The method of claim 8 wherein the temperature is between about 70 and about 90° C.
10. The method of claim 6 wherein the mixture is heated for at least about 2 hours.
11. The method of claim 10 wherein the mixture is heated for not more than about 48 hours.
12. The method of claim 11 wherein the mixture is heated for not more than about 24 hours.
13. The method of claim 12 wherein the mixture is heated for not more than about 12 hours.
14. The method of claim 6 wherein about 0.1-10% by weight of Polymorph A relative to the weight of Polymorph B is added to the mixture prior to heating.
15. The method of claim 14 wherein about 0.2-5% by weight of Polymorph A relative to the weight of Polymorph B is added to the mixture prior to heating.