MK2 inhibitors, synthesis thereof, and intermediates thereto

1. A method for preparing compound I:

or a pharmaceutically acceptable salt thereof, comprising the steps of:

reacting a compound of formula 1-11:

or a salt thereof;

with a compound of formula 1-12,

wherein LG 3 is a suitable leaving group;

under suitable reaction conditions to provide compound I, or a pharmaceutically acceptable salt thereof;

wherein the compound of formula 1-11 is prepared by a process comprising:

reacting a compound of formula 1-10:

or a salt thereof, wherein

R′ is hydrogen or optionally substituted C 1-6 aliphatic or aryl;

under suitable reaction conditions to provide a compound of formula 1-11, or a salt thereof.

2. The method according to claim 1 , wherein a compound of formula 1-10 is prepared by a process comprising:

reacting a compound of formula 1-9:

or a salt thereof, wherein

R 1 is a suitable oxygen protecting group; and

PG 1 is a suitable nitrogen protecting group;

under suitable reaction conditions to provide a compound of formula 1-10, or a salt thereof.

3. The method according to claim 2 , wherein the suitable reaction conditions to provide a compound of formula 1-10, or a salt thereof, comprise an acid.

4. The method according to claim 3 , wherein the acid is HCl or BSA.

5. The method according to claim 2 , wherein a compound of formula 1-10 is provided as an HCl salt.

6. The method according to claim 2 , wherein a compound of formula 1-10 is provided as a BSA salt.

7. The method according to claim 2 , wherein a compound of formula 1-9 is prepared by a process comprising:

reacting a compound of formula 1-7:

or a salt thereof;

with a compound of formula 1-8:

or salt thereof, wherein,

LG 2 is a suitable leaving group;

under suitable reaction conditions to provide a compound of formula 1-9, or a salt thereof.

8. The method according to claim 7 , wherein a compound of formula 1-8 is:

9. The method according to claim 7 , wherein a compound of formula 1-7 is prepared by a process comprising:

reacting a compound of formula 1-5:

or a salt thereof, wherein:

LG 1 is a suitable leaving group; and

R 1 is a suitable oxygen protecting group;

with a compound of formula 1-6:

under suitable reaction conditions to provide a compound of formula 1-7.

10. The method according to claim 9 , wherein a compound of formula 1-5 is prepared by a process comprising:

reacting a compound of formula 1-4:

or a salt thereof;

with a compound of formula R 1 OH under suitable reaction conditions to provide a compound of formula 1-5, or a salt thereof.

11. The method according to claim 10 , wherein the suitable reaction conditions to provide a compound of formula 1-5, or a salt thereof, comprise an activating compound.

12. The method according to claim 10 , wherein a compound of formula 1-4 is prepared by a process comprising:

reacting a compound of formula 1-3:

or a salt thereof;

under suitable reaction conditions to provide a compound of formula 1-4, or a salt thereof.

13. The method according to claim 12 , wherein the suitable reaction conditions to provide a compound of formula 1-4, or a salt thereof, comprise a peroxide reagent.

14. The method according to claim 12 , wherein a compound of formula 1-3 is prepared by a process comprising:

reacting a compound of formula 1-2:

or a salt thereof;

under suitable reaction conditions to provide a compound of formula 1-3, or a salt thereof.

15. The method according to claim 14 , wherein the suitable reaction conditions to provide a compound of formula 1-3, or a salt thereof, comprise a nitrite compound.

16. The method according to claim 15 , wherein the suitable reaction conditions to provide a compound of formula 1-3, or a salt thereof, further comprise a bromide source.

17. The method according to claim 14 , wherein the reaction conditions comprise in situ formation of a diazonium intermediate of formula 1-2a:

wherein X″ is a counterion.

18. The method according to claim 14 , wherein a compound of formula 1-2 is prepared by a process comprising:

reacting a compound of formula 1-1:

or a salt thereof;

under suitable reaction conditions to provide a compound of formula 1-2, or a thereof.

19. The method according to claim 18 , wherein the suitable reaction conditions to provide a compound of formula I-2, or a salt thereof, comprise a cyanating agent.