Compounds and methods for modulating her2

A compound of Formula (I):

• or a pharmaceutically acceptable salt, a tautomer, a stereoisomer, or a deuterated analog thereof, wherein:
• A is N or CH;
• E1 is N or C(CN);
• E2 is C(R4) or N;
• R1 is alkyl, haloalkyl or halogen;
• R2 is —O-alkyl, —O-aryl, —O-heteroaryl, —O-cycloalkyl, —O-heterocycloalkyl, —O— heteroaryl-alkylene-aryl, —NH-alkyl, —NH-aryl, or —NH-heteroaryl, wherein each of the alkyl, aryl, heteroaryl, cycloalkyl or heteocycloalkyl moieties are optionally substituted with 1-4 J1 groups;
• G is -L1-R3 or —W—X—Y;
• L1 is a bond, —C(O)—, —S(O)2—, —N(Rc)—, alkylene, aryl, heteroaryl, heterocycloalkyl, or cycloalkyl, wherein the alkylene, aryl, heteroaryl, heterocycloalkyl, or cycloalkyl are each optionally substituted with 1-4 J2 groups, provided that when L1 is CH2, L1 is not attached to carbon or nitrogen of a saturated ring;
• R3 is a 4-9 membered heterocyclic ring containing at least one nitrogen ring atom, wherein R3 is optionally substituted with 1-4 J3 groups, and wherein one nitrogen atom of R3 is substituted with -L2-R;
• or R3 is a 7-11 membered spirocyclic group containing at least one nitrogen ring atom, wherein the 7-11 membered spirocyclic group containing at least one nitrogen ring atom is optionally substituted with 1-4 J3 groups, and wherein one nitrogen atom of the 7-11 membered spirocyclic group is substituted with -L2-R;
• W is a bond, —C(O)— or —S(O)2—;
• X is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl, each of which is optionally substituted with 1-4 J2 groups;
• Y is —C0-C4alkylene-N(Rd)-L2-R, —C(O)-4-7 membered heterocycloalkyl containing at least one nitrogen atom and substituted with 1-2 oxo groups, -4-7 membered heterocycloalkyl-L2R, —C0-C4alkylene-1-yl-1H-pyrrole-2,5-dione, —C0-C4alkylene-C(H)═C(O)—NH2, —C0-C4alkylene-C(H)═C(H)—C(O)—O-alkyl, —C0-C4alkylene-ethynylene-C(O)—O-alkyl, —C0-C4alkylene-C(H)═C(H)—CN, —C0-C4alkylene-N═C═S, —C0-C4-etheyny, —C0-C4alkylene-ethynyl, —C0-C4alkylene-CN, —C0-C4alkylene-C(H)═N—N(H)Boc, —C0-C4alkylene-C(O)—CH2—Br, —C0-C4alkylene-CH2—Cl, —C0-C4alkylene-oxiranyl, —C0-C4alkylene-SH, —C0-C4alkylene-F, and —C0-C4alkylene-C(H)═O, wherein the C0-C4alkylene moiety is optionally substituted with 1-4 groups independently selected from halogen, cycloalkyl, alkoxy alkoxyalkyl, or hydroxy;
• R4 is H, halo, alkyl, or —O-alkyl;
• L2 is —SO2— or —C(O)—;
• R is ethenyl optionally substituted with 1-3 Q groups, ethynyl optionally substituted with Q, C1-C4 alkylene-NRaRb, —CH2—CN, or haloalkyl wherein one halogen of haloalkyl is on the carbon atom adjacent to L2,
• each Q is independently selected from the group consisting of halogen, haloalkyl, alkyl, alkene, alkyne, —C1-C6alkylene-NRaRb, —C1-C6alkylene-ORc, cyano, hydroxyalkyl, —C0-C6alkylene-C(O)OH, —C1-C6alkylene-C(O)O-alkyl, alkoxyalkyl, —C0-C4alkylene-cycloalkyl optionally substituted with 1-3 J4 groups, —C0-C4alkylene-cycloalkenyl optionally substituted with 1-3 J4 groups, —C0-C4alkylene-7-11 membered spirocyclic cycloalkyl, optionally substituted with 1-3 J4 groups, —C0-C4alkylene-7-11 membered spirocyclic heterocycloalkyl optionally substituted with 1-3 J4 groups, —C0-C4alkylene-heterocycloalkyl optionally substituted with 1-3 J4 groups, and —C0-C4alkylene-heterocycloalkenyl optionally substituted with 1-3 J4 groups;
• or -L2-R is —C═N—OH;
• each J1 is independently selected from the group consisting of halogen, alkyl, haloalkyl, hydroxy, hydroxyalkyl, —C0-C4alkylene-N(H)Rc, alkoxy, and alkoxyalkyl;
• each J2 is independently selected from the group consisting of halogen, alkyl, haloalkyl, hydroxy, hydroxyalkyl, alkoxy, and alkoxyalkyl;
• each J3 is attached to a carbon atom and is independently selected from the group consisting of halogen, haloalkyl, CN, alkyl, hydroxy, hydroxyalkyl, alkoxy, and alkoxyalkyl, or two of the optional 1-4 J3 groups form an oxo group or a 3-6 membered Spiro group, or two of the optional 1-4 J3 groups are on different ring carbon and join to form a 1-3 carbon bridge;
• each J4 is independently selected from the group consisting of halogen, alkyl, haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, oxo, and —C0-C4alkylene-NRaRb, provided that J4 groups can only include up to two oxo groups and up to one —C0-C4alkylene-NRaRb group;
• Ra and Rb each are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, and —C0-C3alkylene-alkynyl optionally substituted with alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, or alkoxyalkyl;
• and
• Rc is selected from the group consisting of H, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups are each optionally substituted with 1-3 groups selected from the group consisting of halogen, alkyl, alkoxy and alkoxyalkyl;
• and
• Rd is selected from the group consisting of H, alkyl, and haloalkyl.