IRAK degraders and uses thereof

1. A compound of formula I-d-5:

or a pharmaceutically acceptable salt thereof, wherein:

each R x is independently —OC 1-6 aliphatic or —CR 2 (OR);

each R is independently hydrogen or C 1-6 aliphatic;

each R y is independently R z , fluoro, chloro, —CN, or —OR;

each R z is a C 1-6 aliphatic optionally substituted with one or more fluoro;

Ring T is selected from phenyl or a 5-9 membered mono- or bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Ring T is further optionally substituted with 1-2 oxo groups;

L x is —C(O)N(H)—, wherein either the carbon or nitrogen atom of —C(O)N(H)— is attached to Ring T;

X is a covalent bond

x is 0 or 1;

y is 0, 1, or 2;

L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C 1-30 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, —CRF—, —CF 2 —, —O—, —N(R)—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O) 2 —, —N(R)S(O) 2 —, —S(O) 2 N(R)—, —N(R)C(O)—, —C(O)N(R)—, —OC(O)N(R)—, —N(R)C(O)O—, wherein

each -Cy- is independently an optionally substituted bivalent ring selected from a 4-7 membered saturated or partially unsaturated carbocyclylenyl, a 4-11 membered saturated or partially unsaturated spiro carbocyclylenyl, a 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 4-11 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and

DIM is a degradation inducing moiety selected from a cereblon E3 ubiquitin ligase binding moiety of formula I-ccc-1:

or a pharmaceutically acceptable salt thereof, wherein:

X 1 is —C(O)—;

X 2a is —C(O)—;

X 3a is —CH 2 — or —C(O)—;

R 1 is hydrogen;

each of R 2 is independently fluoro, chloro, C 1-4 aliphatic, or —OC 1-4 aliphatic;

Ring A a is a fused 6-membered aryl containing 0-1 nitrogen atoms; and

m is 0, or 1.

2. The compound of claim 1 , wherein said compound is of formula I-j-4:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein L is a bivalent, saturated or unsaturated, straight or branched C 1-20 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, —O—, —N(R)—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O) 2 —, —N(R)S(O) 2 —, —S(O) 2 N(R)—, —N(R)C(O)—, —C(O)N(R)—, —OC(O)N(R)—, or —N(R)C(O)O—.

4. The compound of claim 1 , wherein said compound is selected from any one of the following compounds:

or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

6. The compound of claim 1 , wherein the cereblon E3 ubiquitin ligase binding moiety is

7. The compound of claim 1 , wherein R x is

—OMe, —OEt, —OiPr, or

8. The compound of claim 1 , wherein R y is C 1-6 aliphatic optionally substituted with one to three fluoro.

9. The compound of claim 1 , wherein R y is —CN, —CF 3 , fluoro, chloro, —CF 2 Me, —CFMe 2 , -Me, —OMe, or cyclopropyl.

10. The compound of claim 1 , wherein Ring T is a 5-9 membered mono- or bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

11. The compound of claim 1 , wherein Ring T is phenyl,

12. The compound of claim 1 , wherein X is

13. The compound of claim 1 , wherein L is —NR—(CH 2 ) 1-10 —, —(CH 2 ) 1-10 —NR—(CH 2 ) 1-10 —, —(CH 2 ) 1-10 —Cy-NR—(CH 2 ) 1-10 —, —Cy-(CH 2 ) 1-10 —NR—, —Cy-(CH 2 ) 1-10 —NR—(CH 2 ) 1-10 —, —(CH 2 ) 1-10 -Cy-NR—(CH 2 ) 1-10 —, —(CH 2 ) 1-10 -Cy-(CH 2 ) 1-10 —NR—, —(CH 2 ) 1-10 -Cy-(CH 2 ) 1-10 —NR—(CH 2 ) 1-10 —, —Cy-(CH 2 ) 1-10 -Cy-NR—, —Cy-(CH 2 ) 1-10 —NR-Cy-, —Cy-(CH 2 ) 1-10 -Cy-NR—(CH 2 ) 1-10 —, —Cy-(CH 2 ) 1-10 —NR-Cy-(CH 2 ) 1-10 —, —Cy-(CH 2 ) 1-10 —, —(CH 2 ) 1-10 -Cy-(CH 2 ) 1-10 —, —(CH 2 ) 1-10 -Cy-(CH 2 CH 2 O) 1-10 CH 2 CH 2 —, —Cy-(CH 2 ) 1-10 -Cy-, —Cy-(CH 2 ) 1-10 -Cy-(CH 2 ) 1-10 —, —Cy-(CH 2 ) 1-10 -Cy-(CH 2 ) 1-10 -Cy-, or —(CH 2 ) 1-10 -Cy-(CH 2 ) 1-10 -Cy-(CH 2 ) 1-10 —.

14. The compound of claim 1 , wherein -Cy- is

15. The compound of claim 1 , wherein L is