	US 12,221,453 B2
	Substituted pyrazolo[5′,1′:2,3]pyrimido[5,4-b][1,4]oxazines as TYK2 inhibitors
Craig E. Masse, Cambridge, MA (US); Jeremy Robert Greenwood, Brooklyn, NY (US); and Sayan Mondal, New York, NY (US)
Assigned to Takeda Pharmaceutical Company Limited, Osaka (JP)
Filed by TAKEDA PHARMACEUTICAL COMPANY LIMITED, Osaka (JP)
Filed on Jun. 14, 2022, as Appl. No. 17/806,893.
Application 17/806,893 is a continuation of application No. 16/602,000, filed on Oct. 15, 2019, granted, now 11,414,431.
Claims priority of provisional application 62/820,509, filed on Mar. 19, 2019.
Claims priority of provisional application 62/795,869, filed on Jan. 23, 2019.
Claims priority of provisional application 62/745,642, filed on Oct. 15, 2018.
Prior Publication US 2023/0110996 A1, Apr. 13, 2023
Int. Cl. A61K 31/5383 (2006.01); C07D 413/14 (2006.01); C07D 487/04 (2006.01); C07D 519/00 (2006.01)

CPC C07D 519/00 (2013.01) [C07D 487/04 (2013.01)]

3 Claims

1. A compound of Formula I′:

or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:

R¹is -L¹-R^1A;

L¹is a covalent bond;

R^1Ais an 8- to 10-membered heteroaryl ring;

wherein the heteroaryl ring is bicyclic;

wherein the heteroaryl ring has 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;

wherein the heteroaryl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, C_1-6aliphatic, C(O)NRR, OR, a 3- to 7-membered carbocyclic ring, and a 4- to 7-membered heterocyclic ring;

wherein each 3- to 7-membered carbocyclic ring and 4- to 7-membered heterocyclic ring substituent is independently saturated or partially unsaturated;

wherein each 4- to 7-membered heterocyclic ring substituent has 1 or 2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur; and

wherein each 3- to 7-membered carbocyclic ring and 4- to 7-membered heterocyclic ring substituent is optionally and independently substituted with one or more OH substituents;

each R is independently H, C_1-6aliphatic, a 3- to 7-membered heterocyclic ring, phenyl, or a 5- or 6-membered heteroaryl ring;

wherein each heterocyclic ring is independently saturated or partially unsaturated;

wherein each heterocyclic ring independently has 1 or 2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur; and

wherein each heteroaryl ring independently has 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur; or

any two geminal R substituents, taken together with the nitrogen atom to which they are attached, independently form a 4- to 7-membered heterocyclic ring or a 5- or 6-membered heteroaryl ring;

wherein each heterocyclic ring is independently saturated or partially unsaturated; and

wherein each heterocyclic ring and heteroaryl ring independently has 0, 1, 2, or 3 additional heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;

R²is C(O)NHR^2A;

R^2Ais a 3- to 7-membered saturated carbocyclic ring;

wherein the carbocyclic ring is saturated; and

wherein the carbocyclic ring is substituted with n independently selected R^2Csubstituents;

each R^2Cis independently halogen or OH; and

n is 0, 1, or 2.

2. The compound of claim 1, or a stereoisomer thereof, wherein the compound, or stereoisomer thereof, is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.