Bicyclic heterocycles as FGFR4 inhibitors

A compound of Formula (I′):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is N or CR6;
• Y is O or Me;
• R1 is alkyl or haloalkyl;
• R2 is H, halo, alkyl, C1-3 haloalkyl, CN, or C1-3 alkoxy;
• R3 is H, halo, alkyl, C1-3 haloalkyl, CN, or C1-3 alkoxy;
• R4 is alkyl or C1-3 haloalkyl;
• R5 is H, halo, alkyl, C1-3 haloalkyl, CN, or alkoxy;
• R6 is H, halo, CN, ORa4, SRa4, C(O)NRc4Rd4, oC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, NRc4S(O)2Rb4, NRc4S(O)2Rc4, NRc4S(O)2NRc4Rd4, s(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, or a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R6 are each optionally substituted with 1, 2, or 3 substituents independently selected from R10A;
• L is a bond or *—CR7AR7BCR7CR7D—NR7E—, wherein the symbol * indicates the point of attachment to Y in Formula (I′);
• wherein the symbol represents a single or double bond;
• and wherein R7B and R7D are absent when is a double bond;
• RA is selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, C3-7 cycloalkyl, a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R7A are each optionally substituted with 1, 2, or 3 substituents independently selected from R17;
• R7B is H or C1-4 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from R17;
• or R7A and RB together with the carbon atom to which they are attached form a C3-7 cycloalkyl group or a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C3-7 cycloalkyl and 4-7 membered heterocycloalkyl groups are each optionally substituted with 1, 2, or 3 substituents independently selected from R17;
• R7C is selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, C3-7 cycloalkyl, a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl group of R7C are each optionally substituted with 1, 2, or 3 substituents independently selected from R17;
• R7D is H or C1-4 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from R17;
• or R7c and R7D together with the carbon atom to which they are attached form a C3-7 cycloalkyl group or a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C3-7 cycloalkyl and 4-7 membered heterocycloalkyl groups are each optionally substituted with 1, 2, or 3 substituents independently selected from R17;
• R7E is selected from H, C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl;
• alternatively, when is a double bond, R7A and R7c together with the carbon atoms to which they are attached form a phenyl group or a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, wherein said phenyl and 5-6 membered heteroaryl groups are each optionally substituted with 1, 2, or 3 substituents independently selected from R17;
• alternatively, when is a single bond, R7A and R7c together with the carbon atoms to which they are attached form a C3-7 cycloalkyl group or a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C3-7 cycloalkyl group and 4-7 membered heterocycloalkyl group are each optionally substituted with 1, 2, or 3 substituents independently selected from R17;
• alternatively, R7A and R7E together with the carbon and nitrogen atoms to which they are attached form a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 nitrogen atoms, or a 4-7 membered heterocycloalkyl moiety comprising carbon and 1 or 2 nitrogen atoms;
• wherein said 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl group are each optionally substituted with 1, 2, or 3 substituents independently selected from R17;
• alternatively, R7C and R7E together with the carbon and nitrogen atoms to which they are attached form a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 nitrogen atoms, or a 4-7 membered heterocycloalkyl moiety comprising carbon and 1 or 2 nitrogen atoms;
• wherein said 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl group are each optionally substituted with 1, 2, or 3 substituents independently selected from R17;
• R8 is H or C1-4 alkyl which is optionally substituted by halo, CN, ORa9, C(O)NRc9Rd9, NRc9Rd9, NRc9C(O)Rb9, NRc9C(O)ORa9, NRc9C(O)NRc9Rd9, NRc9S(O)Rb9, NRc9S(O)2Rb9, NRc9S(O)2NRc9Rd9, S(O)Rb9, S(O)NRc9Rd9, S(O)2Rb9, S(O)2NRc9Rd9, phenyl, C3-7 cycloalkyl, a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, or a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R8 are each optionally substituted with 1 or 2 R19;
• R10 is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, a 5-10 membered heteroaryl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-10 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl groups of R10 are each optionally substituted with 1, 2, 3, or 4 R10A;
• R10A, at each occurrence, is independently selected from halo, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, C(═NRc4)NRc4Rd4, NRc4C(═NRc4)NRc4Rd4 NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4 NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl group of R10A are each optionally substituted with 1, 2, or 3 substituents independently selected from R19;
• Ra4, Rb4, Rc4, and Rd4, at each occurrence, are independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, phenyl, C3-6 cycloalkyl, a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl group of Ra4, Rb4, Rc4, and Rd4 are each optionally substituted with 1, 2, or 3 substituents independently selected from R19;
• alternatively, Rc4 and Rd4 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 R19;
• Re4 is H or C1-4 alkyl;
• R11 is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
• wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2 or 3 substituents independently selected from R19;
• alternatively, R10 and R11 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 R10A;
• R12 is H or C1-4 alkyl which is optionally substituted by R17;
• R17, at each occurrence, is independently selected from halo, CN, NO2, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rs7, C(═NRe7)NRc7Rd7, NRc7C(═NRe7)NRc7Rd7 NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)ORa7, NRc7C(O)NRc7Rd7 NRc7S(O)Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, S(O)2NRc7Rd7, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R17 are each optionally substituted with 1, 2, or 3 substituents independently selected from R19;
• Ra7, Rb7, Rc7, and Rd7, at each occurrence, are independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, phenyl, C3-6 cycloalkyl, a 5-6 membered heteroaryl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety comprising carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S;
• wherein said C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of Ra7, Rb7, Rc7, and Rd7 are each optionally substituted with 1, 2, or 3 substituents independently selected from R19;
• alternatively, Rc7 and Rd7 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 R19;
• Rc7 is H or C1-4 alkyl;
• R19, at each occurrence, is independently selected from halo, CN, NO2, ORa9, SRa9, C(O)Rb9, C(O)NRc9Rd9, C(O)ORa9, OC(O)Rb9, OC(O)NRc9Rd9, NRc9Rd9, NRc9C(O)Rb9, NRc9C(O)ORa9 NRc9C(O)NRc9Rd9 NRc9S(O)Rb9, NRc9S(O)2Rb9, NRc9S(O)2NRc9Rd9, S(O)Rb9, S(O)NRc9Rd9, S(O)2Rb9, S(O)2NRc9Rd9, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and C1-4 haloalkyl;
• Ra9, Rc9, and Rd9, at each occurrence, are independently selected from H and C1-4 alkyl;
• and
• Rb9 is C1-4 alkyl.