Method for producing a polymorphic form of 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-n-cyclopropyl-4-methylbenzamide
AssigneeMereo Biopharma 1 Limited
InventorsOsama SULEIMAN, Lucia Romero PEREZ, Cornelius Stephan HARLACHER, Stewart JONES
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Abstract
This invention relates to a process for the preparation of Form B of 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide. Also disclosed herein is Form B of 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide, or pharmaceutical compositions thereof, obtainable by the process described herein.
Claims19
A process for the preparation of a crystalline polymorph Form B of 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide, comprising:
- (a) dissolving 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide, at a temperature of at least 40° C., in a non-aqueous solvent or mixture of non-aqueous solvents to obtain a solution, wherein the solvent or solvents contain less than about 5 wt % of water relative to the 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide starting material;
- (b) cooling the solution;
- (c) isolating the crystals;
- (d) heating the resultant crystals to greater than 75° C. for a period of greater than 1 minute to produce Form B 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide.
A process for the preparation of a crystalline polymorph Form B of 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide, comprising:
- (a) dissolving 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide, at a temperature of at least 40° C., in a non-aqueous solvent or mixture of non-aqueous solvents to obtain a solution;
- (b) cooling the solution;
- wherein the final temperature of process step (b) does not exceed 100° C.;
- (c) isolating the crystals;
- (d) heating the resultant crystals to greater than 75° C. for a period of greater than 1 minute to produce Form B 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide.
A process for the preparation of a crystalline polymorph Form B of 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide, comprising:
- (a) dissolving 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide, at a temperature of 90° C. or greater, in a non-aqueous solvent or mixture of non-aqueous solvents to obtain a solution;
- (b) optionally filtering the solution to substantially remove particles having a largest diameter greater than 100 μm;
- (c) cooling the solution to less than 100° C., but greater than 80° C.;
- (d) seeding the solution with Form B crystals of 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide;
- (e) optionally cooling the solution further;
- (f) optionally further seeding of the solution with Form B crystals of 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide;
- (g) cooling the solution to less than 70° C.
- (h) isolating the crystals of Form B 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methylbenzamide.
Dependencies are inferred from the claim text.