Salts of 2-fluoro-N-methyl-4-[7-(quinolin-6-yl-methyl)-imidazo[1,2-B][1,2,4]triazin-2-yl]benzamide and processes related to preparing the same

1. A process of preparing a compound of Formula I:

or salt thereof;

comprising reacting a compound of Formula II:

with a compound of Formula III:

at a temperature from about 120° C. to about 150° C. to form a compound of Formula I, or salt thereof;

wherein X 1 is chloro, bromo, or iodo.

2. The process according to claim 1 , further comprising reacting said compound of Formula I, or salt thereof, with a strong acid to form a compound of Formula IV:

or salt thereof.

3. The process according to claim 2 , wherein said acid is concentrated hydrochloric acid.

4. The process according to claim 2 , further comprising reacting the compound of Formula IV, or salt thereof, with CH 3 NH 2 in the presence of a coupling agent to form a compound of Formula V:

or salt thereof.

5. The process according to claim 4 , wherein said coupling agent is selected from 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxybenzotriazole, (benzotriazol-1-yloxyl)tripyrrolidinophosphonium hexaflurophosphate, and salts thereof.

6. The process according to claim 2 , further comprising:

a) reacting the compound of Formula IV:

or salt thereof, with a halogenating agent, to form a compound of Formula VI:

or salt thereof; and

b) reacting said compound of Formula VI, or salt thereof, with CH 3 NH 2 to form a compound of Formula V:

or salt thereof, wherein X 2 is halogen.

7. The process of claim 6 , wherein said halogenating agent is thionyl chloride.

8. The process of claim 1 , further comprising preparing the compound of Formula II:

by a process comprising reacting a compound of Formula IIa:

with a compound of Formula IIb:

in the presence of a base,

wherein X 1 is chloro, bromo, or iodo.

9. The process of claim 8 , wherein the reacting of the compound of Formula IIa with the compound of Formula IIb is carried out in the presence of proline.

10. The process of claim 8 , wherein X 1 is chloro.

11. The process of claim 8 , further comprising preparing the compound of Formula IIa:

by a process comprising reacting a compound of Formula IIc:

with prop-2-en-1-ol in the presence of a palladium catalyst and a base;

wherein X 3 is chloro, bromo, or iodo.

12. The process of claim 11 , further comprising preparing the compound of Formula IIa:

by a process comprising reacting a compound of Formula IId:

with an acid of formula HX;

wherein X′ is chloro, bromo, or iodo.

13. A process of claim 12 , further comprising preparing a compound of Formula IId:

by a process comprising reducing a compound of Formula IIe:

with hydrogen gas in the presence of a hydrogenation catalyst.

14. A process of claim 13 , wherein the hydrogenation catalyst is palladium-on-carbon.

15. A process of claim 13 , further comprising preparing a compound of Formula IIe by a process comprising reacting a compound of Formula IIc with a compound of Formula IIf:

in the presence of a coupling catalyst and a base.

16. A process of claim 15 , wherein the catalyst is a mixture of palladium acetate and CuI.

17. A process of claim 13 , further comprising preparing a compound of Formula IId:

by a process comprising reacting a compound of Formula IIg:

with 9-borabicyclo[3.3.1]nonane, followed by reacting with a compound of Formula IIc:

in the presence of a coupling catalyst to form the compound of Formula IId;

wherein X 3 is chloro, bromo, or iodo.

18. The process of claim 17 , wherein the coupling catalyst is palladium(II)diacetate.

19. The process of claim 1 , further comprising preparing the compound of Formula III by a process comprising reacting a compound of Formula IIIa:

with a compound of Formula IIIb:

in the presence of a palladium catalyst and a base; wherein:

X 4 is chloro, bromo or iodo; and

each R a is, independently, C 1-6 alkyl; or

each R a , along with the two oxygen atoms and boron atom form a 5- or 6-membered heterocyclic ring; wherein said heterocyclic ring is optionally substituted with 1, 2, 3, or 4 independently selected C 1-4 alkyl groups.

20. The process of claim 19 , wherein the compound of Formula IIIb has formula IIIb-1.

21. The process of claim 19 , further comprising preparing the compound of Formula IIIa by reacting 1,2,4-triazine-3-amine with a halogenating agent.

22. The process of claim 20 , further comprising preparing the compound of Formula IIIb-1 by a process comprising:

a) reacting a compound of Formula IIIc:

a reagent of formula R 1 MgY, followed by reacting with a compound of formula B(OR 2 ) 3 to form a compound of Formula IIId:

and

b) after the reacting in step a), reacting the compound of Formula IIId with an acid, followed by reacting with pinacol to form the compound of Formula IIIb-1;

wherein:

R 1 is C 1-6 alkyl;

each R 2 is, independently, C 1-6 alkyl; and

X 5 is chloro, bromo, or iodo.

23. The process of claim 1 , wherein the polar protic solvent is ethylene glycol.

24. The process of claim 21 , wherein the halogenating agent is N-bromosuccinamide.