US 12,447,153 B2
HER2 mutation inhibitors
Bryan Daniel Ellis, Denver, CO (US); Erik James Hicken, Longmont, CO (US); Ellen Ruth Laird, Longmont, CO (US); Nicholas Charles Lazzara, Denver, CO (US); Bradley Jon Newhouse, Broomfield, CO (US); Spencer Phillip Pajk, Boulder, CO (US); Rachel Zoe Rosen, Broomfield, CO (US); and Russell Andrew Shelp, Boulder, CO (US)
Assigned to Pfizer Inc., New York, NY (US)
Filed by Array BioPharma Inc., Boulder, CO (US)
Filed on Jun. 25, 2022, as Appl. No. 17/849,621.
Claims priority of provisional application 63/350,495, filed on Jun. 9, 2022.
Claims priority of provisional application 63/294,590, filed on Dec. 29, 2021.
Claims priority of provisional application 63/215,435, filed on Jun. 26, 2021.
Prior Publication US 2023/0041385 A1, Feb. 9, 2023
Int. Cl. A61K 31/519 (2006.01); A61K 31/337 (2006.01); A61K 31/44 (2006.01); A61K 31/502 (2006.01); A61K 31/506 (2006.01); A61K 31/5386 (2006.01); A61K 31/55 (2006.01); A61K 31/551 (2006.01); A61K 31/573 (2006.01); A61K 31/655 (2006.01); A61K 31/704 (2006.01); A61K 31/7048 (2006.01); A61K 38/14 (2006.01); A61K 39/395 (2006.01); C07D 471/04 (2006.01); C07D 519/00 (2006.01)
CPC A61K 31/519 (2013.01) [A61K 31/337 (2013.01); A61K 31/44 (2013.01); A61K 31/502 (2013.01); A61K 31/506 (2013.01); A61K 31/5386 (2013.01); A61K 31/55 (2013.01); A61K 31/551 (2013.01); A61K 31/573 (2013.01); A61K 31/655 (2013.01); A61K 31/704 (2013.01); A61K 31/7048 (2013.01); A61K 38/14 (2013.01); A61K 39/3955 (2013.01); C07D 471/04 (2013.01); C07D 519/00 (2013.01)] 18 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
A is selected from carbon and nitrogen, wherein R3 may be bound to A when it is carbon;
R1 is selected from the group consisting of -L1-R5, —NR6R7, N-methyl-3-acrylamide, and prop-1-en-2-yl;
R2 is

OG Complex Work Unit Chemistry
each R3 is independently selected from halogen, methyl, difluoromethyl and trifluoromethyl;
R4 is hydrogen, Cl or methoxy;
L1 is selected from the group consisting of a bond, CHR8, O, NR8 and S;
L2 is selected from NH and 0;
R5 is a 4 to 10 membered heterocycle containing 1 to 3 heteroatoms selected from the group consisting of N, O and S, wherein the heterocycle is substituted by R6, and wherein the heterocycle may be optionally substituted with 1 or 2 groups independently selected from methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, trifluoromethyl methoxymethyl, ethynyl, cyclopropyl, and cyclobutyl;
R6 is selected from the group consisting of cyano, 1-prop-2-en-1-one, 1-(2-fluoroprop-2-en-1-one), 1-(2-methylprop-2-en-1-one), N—(N-methylacrylamide), 1-but-2-yn-1-one, vinylsulfonyl, and (bicyclo[1.1.0]butan-1-yl)methanone;
R7 and R8 are independently hydrogen or methyl; and
n is 0, 1 or 2.