Mutant IDH1 inhibitors useful for treating cancer

A compound of Formula IA:

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is C1-C6haloalkyl, —(C0-C6alkyl)cycloalkyl, phenyl, or a monocyclic or bicyclic heterocycle of 4 to 10 ring atoms having 1, 2, or 3 ring atoms independently chosen from N, S, and O, where R1 is substituted by 0-3 substituents independently chosen from hydroxyl, halogen, cyano, nitro, oxo, —(C0-C6alkyl)phenyl, —O—(C0-C6alkyl)phenyl, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylthio, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, —(C0-C6alkyl)cycloalkyl, —O—(C0-C6alkyl)cycloalkyl, —(C0-C6alkyl)CO2R5, —(C0-C6alkyl)C(O)NR5R6, —(C1-C6alkyl)OR5, —(C0-C6alkyl)NR5R6, —(C0-C6alkyl)NR5C(O)R6, and monocyclic heterocycle of 4 to 6 ring atoms having 1, 2, or 3 ring atoms independently chosen from N, O, and S which monocyclic heterocycle of 4 to 6 ring atoms is optionally substituted with one or more substituents independently chosen from halogen, cyano, —CO2H, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, and C1-C6haloalkoxy;
• R2 is hydrogen, halogen, hydroxyl, cyano, —CO2H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, —(C0-C6alkyl)cycloalkyl, or phenyl, each of which R2 other than hydrogen, halogen, hydroxyl, cyano, and —CO2H can have one or more methylenes replaced with O, S, or N(R5), and can have one or more methines replaced by N, or R2 is a monocyclic heteroaryl of 5 ring atoms having 1 to 4 ring atoms independently chosen from N, O, and S, and each of which R2 other than hydrogen, halogen, hydroxyl, cyano, and —CO2H is optionally substituted with one or more substituents chosen from halogen, hydroxyl, C1-C6alkyl, —OR5, —SR5, NR5R6, C1-C6haloalkyl, phenyl, and C1-C6haloalkoxy;
• R3 is cyano, —C(O)C1-C6alkyl, or —C(O)NR7R8;
• R4 is hydrogen, hydroxyl, halogen, cyano, —CO2H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, or C1-C6haloalkyl;
• A is a phenyl or a monocyclic heteroaryl of 5 or 6 ring atoms having 1 to 4 ring atoms independently chosen from N, O, and S, wherein A is substituted with 0-2 substituents chosen from halogen, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, —(C0-C6alkyl)cycloalkyl, —O(C0-C6alkyl)cycloalkyl, —(C0-C6alkyl)CO2R5, and —(C0-C6alkyl)C(O)NR5R6;
• B is a phenyl, —(C1-C6alkyl)phenyl, —(C2-C6alkenyl)phenyl, —(C2-C6alkynyl)phenyl, C3-C7cycloalkyl, or a monocyclic heterocycle of 5 or 6 ring atoms having 1, 2, or 3 ring atoms independently chosen from N, O, and S, wherein B is substituted with 0-3 substituents independently chosen from hydroxyl, halogen, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, —C0-C2alkylNR5R6, C1-C6haloalkyl, C1-C6haloalkoxy, —(C0-C6alkyl)cycloalkyl, —(C0-C6alkyl)phenyl, —O—(C0-C6alkyl)phenyl, —(C0-C6alkyl)cycloalkyl, —O(C0-C6alkyl)cycloalkyl, —(C0-C6alkyl)CO2R9,
• —(C0-C6alkyl)C(O)NR9R10, —(C0-C6alkyl)NR9R10, and —(C1-C6alkyl)OR9;
• or
• A and B can be taken together to be a bicyclic heteroaryl of 8 to 10 ring atoms, having 1, 2, or 3 ring atoms independently chosen from N, O, and S, wherein the bicyclic heteroaryl is substituted with 0-2 substituents independently chosen from halogen, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, and C1-C6haloalkoxy;
• R5, R6, R7, R9, and R10 are each independently chosen at each occurrence from hydrogen, C1-C6 alkyl, and —(C0-C6alkyl)cycloalkyl;
• R8 is hydrogen, C1-C6 alkyl, —(C0-C6alkyl)cycloalkyl, —(C0-C6alkyl)phenyl, or a 4- to 7-membered heterocycloalkyl ring having 1, 2, or 3 ring atoms independently chosen from N, O, and S, where each R8 is substituted with 0-3 substituents independently chosen from hydroxyl, halogen, oxo, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, —(C0-C6alkyl)cycloalkyl, —(C0-C6alkyl)phenyl, —(C0-C6alkyl)CO2R11, —(C0-C6alkyl)C(O)NR11R12, —(C0-C6alkyl)NR11C(O)R12, —(C1-C6alkyl)OR11, and —(C0-C6alkyl)NR11R12;
• any R5 and R6, or R7 and R8, bound to the same nitrogen atom may be taken together to form a 4- to 7-membered monocyclic heterocycloalkyl ring or 6- to 11-membered bridged bicyclic heterocycloalkyl ring, which heterocycloalkyl ring contains 0, 1, or 2 additional heteroatoms chosen from N, O, and S, which heterocycloalkyl ring is optionally substituted at any carbon ring atom with halogen, hydroxyl, cyano, oxo, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, —(C0-C6alkyl)cycloalkyl, —(C0-C6alkyl)phenyl, —(C0-C6alkyl)CO2R11, —(C0-C6alkyl)C(O)NR11R12, —(C1-C6alkyl)OR11, —(C0-C6alkyl)NR11R12 a spiro fused cycloalkyl ring of 3 to 7 carbons, or a spiro fused heterocycloalkyl ring of 3 to 7 ring atoms with 1 to 3 ring atoms chosen from O, S, and N, the N atoms of said spiro fused heterocycloalkyl ring of 3 to 7 ring atoms are optionally substituted with C1-C6 alkyl, and optionally substituted at any nitrogen ring atom available for substitution with C1-C6 alkyl or (C0-C4alkyl)cycloalkyl;
• any R9 and R10 bound to the same nitrogen atom may be taken together to form a 4 to 7-membered heterocycloalkyl ring, which heterocycloalkyl ring contains 0, 1, or 2 additional heteroatoms chosen from N, O, and S, which heterocycloalkyl ring is optionally substituted at any carbon ring atom with halogen, hydroxyl, oxo, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, —(C0-C6alkyl)cycloalkyl, and optionally substituted at any nitrogen ring atom available for substitution by C1-C6 alkyl or (C0-C4alkyl)cycloalkyl;
• and
• R11 and R12 are each independently chosen at each occurrence from hydrogen, C1-C6 alkyl, and
• —(C0-C6alkyl)cycloalkyl.