TYK2 inhibitors and uses thereof

A compound of formula I′:

• or a pharmaceutically acceptable salt thereof, wherein:
• X is N or C(R3);
• R1 is —CH2F, —CHF2, —NRRD, —N(RD)2, or —ORD;
• R2 is H, RC, —N(R)C(O)Cy2, —N(R)S(O)2Cy2, —N(R)Cy2, —OCy2, —SCy2, or Cy2;
• R3 is H, halogen, or C1-6 aliphatic;
• or
• R2 and R3 are taken together with their intervening atoms to form a 4-7 membered partially unsaturated or aromatic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein said ring is substituted with m instances of R4;
• each of Cy1 and Cy2 is independently phenyl;
• a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring;
• or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy1 is substituted with n instances of R5;
• and;
• wherein Cy2 is substituted with p instances of R6;
• L1 is a covalent bond or a C1-4 bivalent saturated or unsaturated, straight or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by C(R7)2—, N(R)—, —N(R)C(O)—, —C(O)N(R)—, —N(R)S(O)2—, —S(O)2N(R)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)— or —S(O)2—;
• each instance of R4, R5, R6, and R7 is independently RA or RB, and is substituted by q instances of RC;
• each instance of RA is independently oxo, halogen, —CN, —NO2, —OR, —ORD, —SR, —NR2, —S(O)2R, —S(O)(NR)R, —S(O)2NR2, —S(O)R, —S(O)NR2, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)C(NR)NR2, —N(R)S(O)2NR2, —N(R)S(O)2R, —N(RD)S(O)2R, —N(R)S(O)2RD, —N(RD)S(O)2RD, or —P(O)R2;
• each instance of RB is independently C1-6 aliphatic;
• phenyl;
• a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 3-7 membered saturated or partially unsaturated carbocyclic ring;
• a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each instance of Rc is independently oxo, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —S(O)NR2, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)C(NR)NR2, —N(R)S(O)2NR2, or —N(R)S(O)2R or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• RD is a C1-4 aliphatic group wherein one or more hydrogens are replaced by deuterium;
• each R is independently hydrogen, or an optionally substituted group selected from C1.6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:
• two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur;
• and each of m, n, p, and q is independently 0, 1, 2, 3, or 4.