US 12,331,037 B2
Pyrimidines as EGFR-inhibitors and methods of treating disorders
Nathanael S. Gray, Boston, MA (US); Pasi Janne, Needham, MA (US); Hwan Geun Choi, Daegu (KR); and Jaebong Jang, Boston, MA (US)
Assigned to Dana-Farber Cancer Institute, Inc., Boston, MA (US)
Filed by Dana-Farber Cancer Institute, Inc., Boston, MA (US)
Filed on Apr. 28, 2023, as Appl. No. 18/309,164.
Application 18/309,164 is a division of application No. 16/950,465, filed on Nov. 17, 2020, granted, now 11,673,882.
Application 16/950,465 is a division of application No. 16/290,153, filed on Mar. 1, 2019, granted, now 10,870,636, issued on Dec. 22, 2020.
Application 16/290,153 is a division of application No. 15/536,486, granted, now 10,266,517, issued on Apr. 23, 2019, previously published as PCT/US2015/000286, filed on Dec. 23, 2015.
Claims priority of provisional application 62/096,053, filed on Dec. 23, 2014.
Prior Publication US 2023/0348434 A1, Nov. 2, 2023
Int. Cl. C07D 403/04 (2006.01); C07D 403/14 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01)
CPC C07D 403/04 (2013.01) [C07D 403/14 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01)] 16 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or pharmaceutically acceptable salts, hydrates, solvates, stereoisomers, or tautomers thereof, wherein:
Z1, Z2, and Z3 are each N;
R1 is —H, (C1-C4) alkyl, (C1-C4) haloalkyl, —NH2, —NH(C1-C4) alkyl, —N((C1-C4) alkyl)2, or halogen;
R2 is —H or (C1-C6) alkyl;
R3 is (C1-C4) alkoxy, (C1-C4) alkyl, (C1-C4) haloalkyl, or halogen;
R4 is —NR9R10 or a 5—to 7-membered heterocycle comprising 1-3 heteroatoms selected from N, O, and S and optionally substituted with one or more R11;
R9 is —H or (C1-C4) alkyl;
R10 is (C1-C4) alkyl, (C1-C4) alkyl-NH(C1-C4) alkyl, or (C1-C4) alkyl-N((C1-C4) alkyl)2;
or R9 and R10 together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocycle optionally comprising 1 or 2 additional heteroatoms selected from N, O, and S and optionally substituted with one or more R11;
each R11 is independently (C1-C4) alkyl, (C1-C4) haloalkyl, (C1-C4) alkoxy, or halogen;
R5 is —NR12C(O)R13 or —C(O)NR12R13;
R12 is —H or (C1-C6) alkyl;
R13 is (C1-C6) alkyl or (C2-C6) alkenyl, wherein the alkyl or alkenyl is optionally substituted with one or more substituents independently selected from halogen, —OH, —CN, and —NH2;
R6 and R7 together with the nitrogen atom to which they are attached form a substituent of the formula

OG Complex Work Unit Chemistry
wherein
X1, X2, X3, X4, X5 and X6 are each independently N, CH or CR15; and
each R15 is independently (C1-C6) alkyl, (C1-C6) haloalkyl, (C1-C6) alkoxy, —OH, —NH2, —NH(C1-C6) alkyl, —N((C1-C6) alkyl)2, or halogen.