Substituted pyrrolo[2,3-d]pyrimidines as JAK inhibitors

1. A compound of Formula (I′):

or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:

X is CR 11 ;

is phenylene or C 2 -C 9 heteroarylene;

is C 2 -C 9 heterocycloalkylene;

L 1 is C 1 -C 6 alkylene or C 1 -C 6 heteroalkylene;

L 2 is a bond or C 1 -C 6 alkylene;

R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, or C 2 -C 9 heteroaryl, wherein the C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, or C 2 -C 9 heteroaryl is optionally substituted with 1, 2, or 3 independently selected R 5 substituents;

each R 3 is independently halogen, CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 heteroalkyl, C(O)R 8 , C(O)N(R 7 ) 2 , C(O)OR 7 , N(R 7 ) 2 , NR 7 C(O)R 8 , NR 7 S(O) 2 R 8 , OR 7 , S(O) 2 R 8 , or S(O) 2 N(R 7 ) 2;

R 4 is hydrogen, C 1 -C 6 alkyl, or C 1 -C 6 heteroalkyl;

each R 5 is independently halogen, CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 heteroalkyl, C(O)R 8 , C(O)N(R 7 ) 2 , C(O)OR 7 , N(R 7 ) 2 , NR 7 C(O)R 8 , NR 7 S(O) 2 R 8 , OR 7 , =O, S(O) 2 R 8 , or S(O) 2 N(R 7 ) 2;

each R 7 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 heterooalkyl, or C 2 -C 6 alkenyl;

each R 8 is independently C 1 -C 6 alkyl, C 1 -C 6 heterooalkyl, C 2 -C 6 alkenyl, C 3 -C 6 cycloalkyl, or C 2 -C 9 heterocycloalkyl;

R 11 is hydrogen or C 1 -C 6 alkyl, wherein the C 1 -C 6 alkyl is optionally substituted with 1, 2, or 3 independently selected R 5 substituents;

R 12 is hydrogen, halogen, or C 1 -C 6 alkyl;

R 13 is hydrogen or C 1 -C 6 alkyl;

each R 14 is independently C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 heterooalkyl, N(R 7 ) 2 , OR 7 , or =O;

n is 0, 1, 2, or 3; and

p is 0, 1, 2, or 3.

2. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein

is C 2 -C 9 heteroarylene.

3. The compound of claim 2 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein

is pyrrolylene, pyrazolylene, or imidazolylene.

4. The compound of claim 3 , wherein the compound is of Formula (Ia′):

or a pharmaceutically acceptable salt or stereoisomer thereof.

5. The compound of claim 4 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein

is pyrrolidinylene.

6. The compound of claim 5 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each R 14 is independently C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or =O.

7. The compound of claim 6 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each R 14 is independently C 1 -C 6 alkyl.

8. The compound of claim 7 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein p is 1 C 1 -C 6 alkylene.

9. The compound of claim 5 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein L 2 is C 1 -C 6 alkylene.

10. The compound of claim 9 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein L 1 is C 1 -C 6 alkylene.

11. The compound of claim 10 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1 is unsubstituted C 3 -C 9 alkyl.

12. The compound of claim 11 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 4 is hydrogen.

13. The compound of claim 12 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 12 is hydrogen.

14. The compound of claim 13 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein n is 0.

15. The compound of claim 14 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein X is CH.

16. The compound of claim 15 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 13 is C 1 -C 6 alkyl.

17. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient.

18. A method of treating an inflammatory disease or autoimmune disease in a patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof.

19. The method of claim 18 , wherein the inflammatory disease or autoimmune disease is selected from the group consisting of rheumatoid arthritis, multiple sclerosis, psoriasis, lupus, intestinal bowel disease, Crohn's disease, ulcerative colitis, ankylosing spondylitis, vitiligo, and atopic dermatitis.

20. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.