Bicyclic heterocycles as FGFR4 inhibitors

1. A method for inhibiting or ameliorating cancer in a patient, said method comprising: administering to said patient a therapeutically effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

ring A is a C 6-10 arylene, 5 to 6-membered heteroarylene, 5 to 6-membered heterocycloalkylene or C 3-7 eyeloalkylene, wherein the 5 to 6-membered heteroarylene or 5 to 6-membered heterocycloalkylene have carbon and 1 to 4 heteroatoms as ring members selected from O, N and S;

each R 12 is independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a , SR a , C(O)R a , C(O)NR a R a , C(O)OR a , OC(O)R a , OC(O)NR a R a , NR a R a , NR a OR a , NR a C(O)R a , NR a C(O)OR a , NR a C(O)NR a R a , C(═NR a )R a , C(═NR a )NR a R a , NR a C(═NR a )NR a R a , NR a S(O)R a , NR a S(O) 2 R a , NR a S(O) 2 NR a R a , S(O)R a , S(O)NR a R a , S(O) 2 R a , and S(O) 2 NR a R a , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, or 4 R b substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, CN, NO 2 , OR c , SR c , C(O)R c , C(O)NR c R c , C(O)OR c , OC(O)R c , OC(O)NR c R c , C(═NR c )NR c R c , NR c C(═NR c )NR c R c , NR c R c , NR c C(O)R c , NR c C(O)OR c , NR c C(O)NR c R c , NR c S(O)R c , NR c S(O) 2 R c , NR c S(O) 2 NR c R c , S(O)R c , S(O)NR c R c , S(O) 2 R c , and S(O) 2 NR c R c ;

or two adjacent R 12 substituents on ring A taken together with the atoms to which they are attached form a fused 5- or 6-member cycloalkyl ring, 5 to 6-membered heterocycloalkyl ring, phenyl or 5 to 6-membered heteroaryl ring, each of which is optionally substituted with from 1-3 R 10A groups, wherein the heterocycloalkyl or heteroaryl have 1-2 heteroatoms as ring members selected from O, N and S;

each R a is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 R d substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, halo, CN, OR e , SR e , C(O)R e , C(O)NR e R e , C(O)OR e , OC(O)R e , OC(O)NR e R e , NR e R e , NR e C(O)R e , NR e C(O)NR e R e , NR e C(O)OR e , C(═NR e )NR e R e , NR e C(═NR e )NR e R e , S(O)R e , S(O)NR e R e , S(O) 2 R e , NR e S(O) 2 R e , NR e S(O) 2 NR e R e , and S(O) 2 NR e R e ;

each R c is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 R f substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, halo, CN, OR g , SR g , C(O)R g , C(O)NR g R g , C(O)OR g , OC(O)R g , OC(O)NR g R g , NR g R g , NR g C(O)R g , NR g C(O)NR g R g , NR g C(O)OR g , C(═NR g )NR g R g , NR g C(═NR g )NR g R g , S(O)R g , S(O)NR g R g , S(O) 2 R g , NR g S(O) 2 R g , NR g S(O) 2 NR g R g , and S(O) 2 NR g R g ;

or any two R a substituents, attached to the same nitrogen atom, together with the nitrogen atom to which they are attached, a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;

each R h is independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR i , SR i , C(O)R i , C(O)NR i R i , C(O)OR i , OC(O)R i , OC(O)NR i R i , NR i R i , NR i C(O)R i , NR i C(O)NR i R i , NR i C(O)OR i , C(═NR i )NR i R i , NR i C(═NR i )NR i R i , S(O)R i , S(O)NR i R i , S(O) 2 R i , NR i S(O) 2 R i , NR i S(O) 2 NR i R i , and S(O) 2 NR i R i , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 independently selected R j substituents;

each R j is independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, CN, OR k , SR k , C(O)R k , C(O)NR k R k , C(O)OR k , OC(O)R k , OC(O)NR k R k , NR k R k , NR k C(O)R k , NR k C(O)NR k R k , NR k C(O)OR i , C(═NR k )NR k R k , NR k C(═NR k )NR k R k , S(O)R k , S(O)NR k R k , S(O) 2 R k , NR k S(O) 2 R k , NR k S(O) 2 NR k R k , and S(O) 2 NR k R k ;

or any two R c substituents, attached to the same nitrogen atom, together with the nitrogen atom to which they are attached, a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;

or any two R e substituents, attached to the same nitrogen atom, together with the nitrogen atom to which they are attached, a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;

or any two R g substituents, attached to the same nitrogen atom, together with the nitrogen atom to which they are attached, a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;

or any two R i substituents, attached to the same nitrogen atom, together with the nitrogen atom to which they are attached, a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected R h substituents;

each R e , R g , R i or R k is independently selected from H, C 1-4 alkyl, C 6-10 aryl, C 1-4 haloalkyl, C 2-4 alkenyl, and C 2-4 alkynyl, wherein the C 1-4 alkyl, C 6-10 aryl, C 2-4 alkenyl or C 2-4 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylthio, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 haloalkyl, and C 1-4 haloalkoxy;

L is NR 9 or a bond, wherein R 9 is H or C 1-6 alkyl;

X 1 is —CR 10 R 11 ;

X 2 is N or CR 6 ;

R 1 is C 1-3 alkyl or C 1-3 haloalkyl;

R 2 is H, halo, C 1-3 alkyl, C 1-3 haloalkyl, CN, or C 1-3 alkoxy;

R 3 is H, halo, C 1-3 alkyl, C 1-3 haloalkyl, CN, or C 1-3 alkoxy;

R 4 is C 1-3 alkyl or C 1-3 haloalkyl;

R 5 is H, halo, C 1-3 alkyl, C 1-3 haloalkyl, CN, or C 1-3 alkoxy;

R 6 is selected from H, halo, CN, OR a4 , SR a4 , C(O)NR c4 R d4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , S(O) 2 NR c4 R d4 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, phenyl, C 3-6 cycloalkyl, a 5-6 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R 6 are each optionally substituted with 1, 2, or 3 substituents independently selected from R 10A ;

R 8a and R 8b are each independently H, halogen, methyl, or CF 3 ;

R 8c is H or C 1-4 alkyl optionally substituted with R 17 ;

R 10 and R 11 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, a 5-10 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-10 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl groups of R 10 and R 11 are each optionally substituted with 1, 2, 3, or 4 R 10A ;

R 10A , at each occurrence, is independently selected from halo, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 S(O) 2 NR c4 R d4 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, phenyl, C 3-6 cycloalkyl, a 5-6 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R 10A are each optionally substituted with 1, 2, or 3 substituents independently selected from R 19 ;

R a4 , R b4 , R c4 , and R d4 , at each occurrence, are independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, phenyl, C 3-6 cycloalkyl, a 5-6 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, phenyl, C 3-6 , cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R a4 , R b4 , R c4 , and R d4 are each optionally substituted with 1, 2, or 3 substituents independently selected from R 19 ;

alternatively, R c4 and R d4 together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group which is optionally substituted with 1, 2 or 3 substituents independently selected from R 19 ;

R e4 is H or C 1-4 alkyl;

alternatively, R 10 and R 11 together with the carbon atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl group or a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocycloalkyl group; wherein said 3-, 4-, 5-, 6-, or 7-membered cycloalkyl group and 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocycloalkyl group are each optionally substituted with 1, 2, 3 or 4 R 10A ;

R 17 , at each occurrence, is independently selected from halo, CN, NO 2 , OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)OR a7 , NR c7 C(O)NR c7 R d7 , NR c7 S(O)R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , S(O) 2 NR c7 R d7 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, phenyl, C 3-6 cycloalkyl, a 5-6 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R 17 are each optionally substituted with 1, 2, or 3 substituents independently selected from R 19 ;

R a7 , R b7 , R c7 , and R d7 , at each occurrence, are independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, phenyl, C 3-6 cycloalkyl, a 5-6 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R a7 , R b7 , R c7 , and R d7 are each optionally substituted with 1, 2, or 3 substituents independently selected from R 19 ;

alternatively, R c7 and R d7 together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group which is optionally substituted with 1, 2 or 3 substituents independently selected from R 19 ;

R e7 is H or C 1-4 alkyl;

R 19 , at each occurrence, is independently selected from halo, CN, NO 2 , OR a9 , SR a9 , C(O)R b9 , C(O)NR c9 R d9 , C(O)OR a9 , OC(O)R b9 , OC(O)NR c9 R d9 , NR c9 R d9 , NR c9 C(O)R b9 , NR c9 C(O)OR a9 , NR c9 C(O)NR c9 R d9 , NR c9 S(O)R b9 , NR c9 S(O) 2 R b9 , NR c9 S(O) 2 NR c9 R d9 , S(O)R b9 , S(O)NR c9 R d9 , S(O) 2 R b9 , S(O) 2 NR c9 R d9 , C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and C 1-4 haloalkyl;

R a9 , R c9 , and R d9 , at each occurrence, are independently selected from H and C 1-4 alkyl;

R b9 is C 1-4 alkyl; and

the subscript n is 1, 2 or 3

wherein said cancer is hepatocellular carcinoma, rhabdomyosarcoma, head and neck cancer, ovarian cancer, cholangiocellular carcinoma, or breast cancer.

2. The method of claim 1 , wherein the compound is a compound of Formula (Ia):

or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein the compound is a compound of Formula (Id):

or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 , wherein ring A is C 6-10 arylene.

5. The method of claim 1 , wherein ring A is 1,3-phenylene.

6. The method of claim 1 , wherein ring A is 5-membered heteroarylene.

7. The method of claim 1 , wherein ring A is a 5-membered heteroarylene selected from pyrrol-2,5-diyl, pyrrol-1,2-diyl, pyrrol-3,4-diyl, pyrrol-2,3-diyl, pyrrol-1,3-diyl, pyrrol-1,4-diyl, pyrazol-1,3-diyl, pyrazol-1,4-diyl, pyrazol-1,5-diyl, pyrazol-3,4-diyl, pyrazol-4,5-diyl, pyrazol-3,5-diyl, imidazol-1,2-diyl, imidazol-1,4-diyl, imidazol-1,5-diyl, imidazol-2,4-yl, imidazol-2,5-diyl, triazol-diyl, tetrazol-diyl, oxazol-2,5-diyl, oxazol-2,4-diyl, thiophen-2,3-diyl, thiophen-2,4-diyl, thiophen-2,5-diyl, thiazol-2,4-diyl, thiazol-2,5-diyl, isoxazol-3,4-diyl, isoxazol-3,5-diyl, isothiazol-3,4-diyl, isothiazol-3,5-diyl, furan-2,3-diyl, furan-2,4-diyl or furan-2,5-diyl.

8. The method of claim 1 , wherein ring A is 6-membered heteroarylene.

9. The method of claim 1 , wherein ring A is a 6-membered heteroarylene selected from pyridin-2,3-diyl, pyridin-2,4-diyl, pyridin-2,5-diyl, pyridin-2,6-diyl, pyridin-3,4-diyl, pyridin-3,5-diyl, pyrazin-2,3-diyl, pyrazin-2,5-diyl, pyrazin-2,6-diyl, pyridazin-3,4-yl, pyridazin-3,5-yl, pyridazin-3,6-yl, pyridazin-4,5-yl, pyridazin-4,6-yl, primidin-2,4-diyl, primidin-2,5-diyl, primidin-4,5-diyl, primidin-4,6-diyl, or triazin-diyl.

10. The method of claim 1 , wherein ring A is cycloalkylene selected from cycloprop-1,2-diyl, cyclobut-1,2-diyl, cyclobut-1,3-diyl, cyclopent-1,2-diyl, cyclopent-1,3-diyl, cyclohex-1,2-diyl, cyclohex-1,3-diyl, cyclohex-1,4-diyl, cyclohept-1,2-diyl, cyclohept-1,3-diyl or cyclohept-1,4-diyl.

11. The method of claim 1 , wherein ring A is heterocycloalkylene.

12. The method of claim 1 , wherein R 2 and R 5 are halogen.

13. The method of claim 1 , wherein R 2 and R 5 are F.

14. The method of claim 1 , wherein R 1 and R 4 are each independently C 1-3 alkyl.

15. The method of claim 1 , wherein R 1 and R 4 are each independently methyl.

16. The method of claim 1 , wherein R 10 and R 11 are each independently C 1-6 alkyl.

17. The method of claim 1 , wherein R 10 and R 11 are methyl.

18. The method of claim 1 , wherein R 10 and R 11 together with the carbon atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl group, which is optionally substituted with 1 or 2 independently selected R 10A groups.

19. The method of claim 1 , wherein R 10 and R 11 together with the carbon atom to which they are attached form a cyclopropyl, optionally substituted with 1 or 2 independently selected R 10A groups.

20. The method of claim 1 , wherein R 10 and R 11 together with the carbon atom to which they are attached form 4-, 5-, 6-, or 7-membered heterocycloalkyl group, which is optionally substituted with 1 or 2 independently selected R 10A groups.

21. The method of claim 1 , wherein X 2 is N or CH.

22. The method of claim 1 , wherein each R 12 is independently H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, OR a , SR a , C(O)R a , C(O)NR a R a , C(O)OR a , OC(O)R a , OC(O)NR a R a , NR a R a , NR a OR a , NR a C(O)R a , NR a C(O)OR a , NR a C(O)NR a R a , NR a S(O)R a , NR a S(O) 2 R a , NR a S(O) 2 NR a R a , S(O)R a , S(O)NR a R a , S(O) 2 R a , and S(O) 2 NR a R a , wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2 or 3 R b substituents.

23. The method of claim 1 , wherein each R 12 is independently —NH 2 , —NHOH, —NHOR a , —NHR a , —NHC(O)R a , —NHC(O)NHR a , C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-4 haloalkoxy, halo, CN or 4 to 6-membered heterocycloalkyl, wherein C 1-6 alkyl, C 1-6 haloalkyl, or 4 to 6-membered heterocycloalkyl is optionally substituted with from 1-3 R b ; and C 1-6 alkoxy or C 1-4 haloalkoxy is optionally substituted by 1-3 R d .

24. The method of claim 1 , wherein each R 12 is independently NH 2 , CH 3 , F, CN, 4-piperidinyl, 4-piperazinyl or 4-morpholinyl.

25. The method of claim 1 , wherein R 3 is H.

26. The method of claim 1 , wherein L is a bond or NH.

27. The method of claim 1 , wherein n is 1 or 2.

28. The method of claim 1 , wherein the compound is selected from:

N-{3-[2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridin]-6′-yl]phenyl}acrylamide;

N-(3-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-4-methylphenyl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′[2,7]naphthyridine]-6′-yl)pyridin-3-yl)acrylamide;

N-(4-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)pyridin-2-yl)acrylamide;

N-(4-cyano-3-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)phenyl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-2-fluoro-4-methylphenyl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-6-methylpyridin-3-yl)acrylamide;

6′-(1-acryloylpiperidin-3-yl)-2′-(2,6-difluoro-3,5-dimethoxyphenyl)-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridin]-3′(2′H)-one; and

N-(3-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)phenyl)-N-methylacrylamide;

or a pharmaceutically acceptable salt thereof.

29. The method of claim 1 , wherein the compound is selected from:

N-{3-[2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro- 1 ′H-spiro[cyclopropane-1,4′-[2,7]naphthyridin]-6′-yl]-5-morpholin-4-ylphenyl}acrylamide;

N-[3-[2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridin]-6′-yl]-5-(morpholin-4-ylmethyl)phenyl]acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-2-(morpholinomethyl)phenyl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-2-(hydroxymethyl)phenyl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(2-methoxyethyl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(2-ethoxyethyl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(2-hydroxyethyl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(2-morpholinoethyl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(2-(methylamino)-2-oxoethyl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(pyridin-4-ylmethyl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(pyridin-3-ylmethyl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′, 3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)- 1-((1-methyl- 1H- 1,2,4-triazol-3-yl)methyl)-1H-pyrazol-4-ypacrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′, 3′-dihydro-l′H-spiro[cyclopropane- 1,4′- [2, 7]naphthyridine]-6′-yl)- 1 -((tetrahydro-2H-pyran-4-yl)methyl)- 1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3, 5-dimethoxyphenyl)-3′-oxo-2′, 3′-dihydro-l′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)- 1-(isoxazol-3-ylmethyl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′, 3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2, 7]naphthyridine]-6′-yl)- 1-((1-methyl- 1H-pyrazol-5-yl)methyl)-1H-pyrazol-4-yl)acrylamide;

N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′, 3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2, 7]naphthyridine]-6′-yl)-1-((1-methyl-1H-pyrazol-4-yl)methyl)-1H-pyrazol-4-yl)acrylamide

(S)-N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrazol-4-yl)acrylamide;

(R)-N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrazol-4-yl)acrylamide;

(R)-N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-((tetrahydrofuran-2-yl)methyl)- 1H-pyrazol-4-yl)acrylamide;

(S)-N-(5-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-((tetrahydrofuran-2-yl)methyl)-1H-pyrazol-4-yl)acrylamide;

N-(3-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(2-methoxyethyl)-1H-pyrazol-4-yl)acrylamide;

N-(3-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(2-(trifluoromethoxy)ethyl)-1H-pyrazol-4-yl)acrylamide;

N-(3-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(2-morpholinoethyl)-1H-pyrazol-4-yl)acrylamide;

N-(3-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)acrylamide;

N-(3-(2′-(2,6-difluoro-3,5-dimethoxyphenyl)-3′-oxo-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-[2,7]naphthyridine]-6′-yl)-1-(2-(dimethylamino)-2-oxoethyl)-1H-pyrazol-4-yl)acrylamide; and

N-(3-(6′-(2,6-difluoro-3,5-dimethoxyphenyl)-7′-oxo-6′,7′-dihydro-5′H-spiro[cyclopropane-1,8′-pyrido[4,3-d]pyrimidine]-2′-yl)-4-methylphenyl)acrylamide; or a pharmaceutically acceptable salt thereof.

30. The method of claim 1 , wherein said cancer is hepatocellular carcinoma.

31. The method of claim 1 , wherein said cancer is rhabdomyosarcoma.

32. The method of claim 1 , wherein said cancer is head and neck cancer.

33. The method of claim 1 , wherein said cancer is ovarian cancer.

34. The method of claim 1 , wherein said cancer is cholangiocellular carcinoma.

35. The method of claim 1 , wherein said cancer is breast cancer.