US 11,932,648 B2
CDK2 inhibitors
Douglas Wilson, Ayer, MA (US); Neil Bifulco, Jr., Sudbury, MA (US); Natasja Brooijmans, Boston, MA (US); Joseph L. Kim, Wayland, MA (US); Emanuele Perola, Cambridge, MA (US); Philip D. Ramsden, Cambridge, MA (US); Richard Vargas, Cambridge, MA (US); and Steven Mark Wenglowsky, Cambridge, MA (US)
Assigned to BLUEPRINT MEDICINES CORPORATION, Cambridge, MA (US)
Filed by BLUEPRINT MEDICINES CORPORATION, Cambridge, MA (US)
Filed on Jun. 27, 2022, as Appl. No. 17/850,453.
Claims priority of provisional application 63/215,901, filed on Jun. 28, 2021.
Prior Publication US 2023/0159535 A1, May 25, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 487/04 (2006.01); A61K 31/4985 (2006.01); A61K 31/519 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 519/00 (2013.01); C07B 2200/05 (2013.01)] 18 Claims
 
1. A compound of Formula (Ia),

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
R1 is C1-C4alkyl optionally substituted with 1 to 4 groups each independently selected from halo and D;
R2 is C1-C4 alkyl or Ring A, wherein the C1-C4alkyl is optionally substituted with 1 to 4 groups each independently selected from halo, D, CN, and OH and/or 1 group of 5 to 6 membered heteroaryl having 1 to 3 ring heteroatoms each independently selected from the group consisting of O, S, N, and NRd; and
R3 is selected from the group consisting of H, D, C1-C4 alkyl, C3-C10cycloalkyl, and 4 to 12-membered heterocyclyl, wherein the C1-C4alkyl and C3-C10cycloalkyl are each optionally substituted with 1 to 4 Rc, wherein the 4 to 12-membered heterocyclyl has 1 to 4 ring heteroatoms each independently selected from the group consisting of O, S, N, and NRd and then is optionally substituted on a ring carbon with 1 to 4 Rc; or
R2 and R3 are taken together with the carbon atom to which they are attached to form Ring B, wherein Ring B is C3-C10cycloalkyl or 4 to 12-membered heterocyclyl, wherein the C3-C10cycloalkyl is optionally substituted with 1 to 4 Rb, wherein the 4 to 12-membered heterocyclyl has 1 to 4 ring heteroatoms each independently selected from the group consisting of NRd, N, O, and S and then is optionally substituted on a ring carbon by 1 to 4 Rb;
Ring A is selected from the group consisting of C3-C10cycloalkyl, phenyl, naphthyl, 4 to 12-membered heterocyclyl, and 4 to 12-membered heteroaryl, wherein the C3-C10cycloalkyl, phenyl, and naphthyl are each optionally substituted with 1 to 4 Ra, wherein the 4 to 12-membered heterocyclyl and 4 to 12-membered heteroaryl have 1 to 4 ring heteroatoms each independently selected from the group consisting of O, S, N, and NRd and then are optionally substituted on a ring carbon with 1 to 4 Ra;
Each Ra is independently selected from the group consisting of D, halo, OH, CN, C1-C4alkyl, and C1-C4alkoxy, or two Ra, attached to the same atom, form a ═O, wherein the C1-C4alkyl and C1-C4alkoxy are each optionally substituted with 1 to 4 groups each independently selected from the group consisting of halo, OH and CN;
Each Rb is independently selected from the group consisting of D, halo, OH, CN, C1-C4alkyl, and C1-C4alkoxy, or two Rb, attached to the same atom, form a ═O, wherein the C1-C4 alkyl and C1-C4 alkoxy are each optionally substituted with 1 to 4 groups each independently selected from the group consisting of halo, OH and CN;
Each Rc is independently selected from the group consisting of D, halo, OH, CN, C1-C4alkyl, and C1-C4alkoxy, or two Rc, attached to the same atom, form a ═O, wherein the C1-C4alkyl and C1-C4alkoxy are each optionally substituted with 1 to 4 groups each independently selected from the group consisting of halo, OH, and CN; or
Each Rd is independently selected from the group consisting of H, D, and C1-C6alkyl;
R4 is selected from the group consisting of H, D, and C1-C4alkyl optionally substituted with 1 to 4 groups each independently selected from halo, D and OH;
R5 is selected from the group consisting of H, D, halo, CN, and C1-C4alkyl, wherein the C1-C4alkyl is optionally substituted with 1 to 4 groups each independently selected from halo and OH;
R6 is H or D; and
R7 is H or D.