Crystalline form of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-D3) pyridazine-3-carboxamide

Patent metadata

Field	Value
Publication number	US-11613529-B2
Application number	US-201917058698-A
Country	US
Kind code	B2
Filing date	May 30, 2019
Priority date	May 31, 2018
Publication date	Mar 28, 2023
Grant date	Mar 28, 2023

Abstract

Disclosed is crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methy-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-methyl-d3)pyridazine-3-carboxamide. Form B is the HCl salt of a neat crystalline form. Characterization data for Form B are disclosed.

First claim

What is claimed is:

1. A method of preparing crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, comprising:
(a) mixing 51 milligrams of Compound (I), which is 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, and 0.5 mL of 0.25 M HCl into 2 mL of IPA, thereby forming a mixture;
(b) heating and stirring the mixture; and
(c) stirring the mixture without heating,
to obtain crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide.

2. The method according to claim 1 , wherein the heating and stirring in (b) is performed at 55° C.

3. Crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide produced by the method according to claim 1 , having a purity of greater than 90 wt %.

4. A method of preparing crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, comprising:
(a) forming a solution by mixing 550 milligrams of Compound (I), which is 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, into 35 mL of THE and 2 mL of water;
(b) adding 108 microliters of 37% HCl to the solution, thereby forming a first slurry;
(c) drying the first slurry to obtain a solid;
(d) suspending the solid in 5 mL of BuOAc, thereby forming a second slurry;
(e) aging the second slurry to obtain an aged slurry;
(f) filtering the aged slurry to obtain a wet cake; and
(g) drying the wet cake,
to obtain crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide.

5. The method according to claim 4 , wherein the suspending in (d) is performed at 60° C., and wherein the aging in (e) is performed at 60° C.

6. The method according to claim 4 , wherein the drying in (g) is performed at a temperature of from 50° C. to 60° C.

7. Crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide produced by the method according to claim 4 , having a purity of greater than 90 wt %.

8. A method of preparing crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, comprising:
(a) forming a solution by mixing 2 grams of Compound (I), which is 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, and 15 mL of DMA;
(b) forming an HCl solution by mixing 395 microliters of 37% HCl, 25 mL of BuOAc, and 7.6 mL of DMA;
(c) adding, to the solution formed in (a), the following:
(i) 3 mL of the HCl solution;
(ii) 40 mg of Compound (I) Form B seeds; and
(iii) the remaining HCl solution, thereby forming a slurry;

(d) cooling the slurry;
(e) stirring the slurry;
(f) further cooling the slurry, followed by further stirring the slurry;
(g) filtering the slurry to obtain a wet cake;
(h) washing the wet cake with 6 mL of BuOAc; and
(i) drying the wet cake,
to obtain crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide.

9. The method according to claim 8 , wherein forming the solution in (a) is performed at 60° C., and wherein forming the HCl solution in (b) is performed at 60° C.

10. The method according to claim 8 , wherein adding the remaining HCl solution in (e) is performed over a time period of at least 3 hours.

11. The method according to claim 8 , wherein in (d), the slurry is cooled from 60° C. to 50° C., over a time period of 1 hour.

12. The method according to claim 8 , wherein the stirring in (e) is performed at 50° C. for at least 15 hours.

13. The method according to claim 8 , wherein the further cooling in (f) is performed by cooling the slurry to 20° C., over a time period of 1 hour.

14. The method according to claim 8 , wherein in (i), the wet cake is dried in a vacuum oven at a temperature of 50° C.

15. Crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide produced by the method according to claim 8 , having a purity of greater than 90 wt %.

16. A method of preparing crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, comprising:
(a) forming a solution by combining 1.4 kilograms of Compound (I), which is 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, and 8.4 liters of NMP and applying heat;
(b) polish filtering the solution, thereby obtaining a polish filtered solution;
(c) heating the polish filtered solution and adding 0.421 kilograms of HCl 37 wt % solution to the polish filtered solution;
(e) adding 14 liters of ethyl acetate to obtain a slurry;
(f) cooling the slurry to obtain a cooled slurry;
(g) aging the cooled slurry to obtain an aged slurry;
(h) filtering the aged slurry to obtain a wet cake; and
(i) drying the wet cake,
to obtain crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide.

17. The method according to claim 16 ,
wherein the applying heat in (a) is performed at 50° C.,
wherein the polish filtering in (b) is performed at 50° C., and
wherein in (c), the polish filtered solution is heated to 50° C.

18. The method according to claim 16 , wherein in (f), the slurry is cooled to 20° C., over a time period of 1 hour.

19. The method according to claim 16 , wherein in (g), the cooled slurry is aged for 12 hours.

20. The method according to claim 16 , further comprising washing the wet cake obtained in (h) with ethyl acetate.

21. The method according to claim 16 , wherein in (i), the wet cake is dried in a vacuum oven at a temperature of 55° C.

22. Crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide produced by the method according to claim 16 , having a purity of greater than 90 wt %.

23. A method of preparing crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, comprising:
(a) forming a solution by combining 2.323 kilograms of Compound (I), which is 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d 3 )pyridazine-3-carboxamide, and 16.26 liters of NMP and applying heat;
(b) polish filtering the solution, thereby obtaining a polish filtered solution;
(c) heating the polish filtered solution and adding 0.55 kilograms of HCl 37 wt % solution to the polish filtered solution;
(e) adding 0.04 kilograms of Compound (I) Form B seeds and 0.47 liters of ethyl acetate to obtain a slurry;
(f) aging the slurry to obtain a first ag

Assignees

• Bristol Myers Squibb Co

Inventors

• Roberts Daniel Richard

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61P17/06

  Antipsoriatics · CPC title