Compounds useful as protein kinase inhibitors

A method of treating a PLK-mediated disorder wherein the disorder is cancer in a patient, comprising administering to said patient in need thereof a compound of formula I:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• X1 is a bond, O, NR8, S, SO, or SO2;
• X2 is N;
• R1 is H, C1-10 aliphatic, C3-10 cycloaliphatic, C6-10 aryl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocyclyl;
• wherein said R1 is optionally substituted with 0-5 J1;
• each of R2 and R3 is independently H, C1-10 aliphatic, or C3-10 cycloaliphatic;
• wherein each R2 and R3 is optionally and independently substituted with 0-5 J2 and J3 respectively;
• and
• R2 and R3, together with the carbon atom to which they are attached, form a 3- to 8-membered saturated or partially unsaturated monocyclic ring containing 0-4 heteroatoms each independently selected from O, N, and S;
• said monocyclic ring formed by R2 and R3 is optionally substituted with 0-4 J23;
• R4 is H, C(O)R, C(O)OR, or C(O)NRR′, C1-10aliphatic, C3-10 cycloaliphatic, C6-10 aryl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocyclyl, —(C1-6 aliphatic)-(C3-10 cycloaliphatic), —(C1-6 aliphatic)-(C6-10 aryl), or —(C1-6 aliphatic)-(5- to 10-membered heteroaryl);
• and R4 is optionally substituted with 0-5 J4;
• or
• R2 and R4, together with the atoms to which they are attached, form a 3- to 8-membered saturated or partially unsaturated monocyclic ring containing 0-4 heteroatoms each independently selected from O, N, and S;
• said monocyclic ring formed by R2 and R4 is optionally substituted with 0-4 J24;
• R5 is H, CO2R, CH2OR, CONR2, CN, F, or CF3;
• L is a bond;
• each of R6 and R7 is independently H, C1-10 aliphatic, or C3-10 cycloaliphatic;
• wherein each of R6 and R7 is optionally and independently substituted with 0-5 J6 and J7 respectively;
• or
• R6 and R7, together with the carbon atom to which they are attached, form a 3- to 8-membered saturated or partially unsaturated monocyclic ring containing 0-4 heteroatoms each independently selected from O, N, and S;
• said monocyclic ring formed by R6 and R7 is optionally substituted with 0-4 J67;
• or
• R2 and R6, together with the carbon atom to which they are attached, form a 3- to 8-membered saturated or partially unsaturated monocyclic ring containing 0-4 heteroatoms each independently selected from O, N, and S;
• said monocyclic ring formed by R2 and R6 is optionally substituted with 0-4 J26;
• or
• R4 and R6, together with the carbon atom to which they are attached, form a 3- to 8-membered saturated or partially unsaturated monocyclic ring containing 0-4 heteroatoms each independently selected from O, N, and S;
• said monocyclic ring formed by R4 and R6 is optionally substituted with 0-4 J46;
• R8 is H, C1-6 aliphatic, C3-8 cycloaliphatic, C(O)R, C(O)OR, or C(O)NRR′;
• or
• each J1 is independently C1-6haloalkyl, halo, NO2, CN, Q, or —Z-Q;
• or, two J1 taken together can optionally form ═O;
• Z is C1-6 aliphatic optionally replaced with 0-3 occurrences of —NR—, —O—, —S—, —C(O)—, —C(═NR)—, —C(═NOR)—, —SO—, or —SO2—;
• each Z is optionally substituted with 0-2 Jz;
• Q is H;
• C1-6 aliphatic;
• a 3- to 8-membered aromatic or nonaromatic monocyclic ring having 0-3 heteroatoms independently selected from O, N, and S;
• or an 8-12 membered aromatic or nonaromatic bicyclic ring system having 0-5 heteroatoms independently selected from O, N, and S;
• each Q is optionally substituted with 0-5 JQ;
• each of J2, J3, J6, and J7 is independently C1-6 aliphatic, C3-6 cycloaliphatic, or —(C1-4 alkyl)n-V1;
• wherein
• n is 0 or 1;
• V is halo(C1-4 aliphatic), —O(haloC1-4 aliphatic), halo, NO2, CN, OH, OR″, SH, SR″, NH2, NHR″, N(R″)2, COH, COR″, CO2H, CO2R″, CONH2, CONHR″, CONR″2, OCOR″, OCONH2, OCONHR″, OCON(R″)2, NHCOR″, NR″COR″, NHCO2R″, NR″CO2R″, NHCO2H, NR″CO2H, NHCONH2, NHCONHR″, NHCON(R″)2, SO2NH2, SO2NHR″, SO2N(R″)2, NHSO2R″, or NR″SO2R″;
• or V1 is a cyclic group selected from C3-6cycloaliphatic, phenyl, 5- to 6-membered heteroaryl, or 3- to 6-membered heterocyclyl;
• wherein said cyclic group is optionally substituted with 0-3 Jv;
• R″ is unsubstituted C1-4 aliphatic;
• or two of the same J2, J3, J6, and J7 bonded to the same atom, together can optionally form ═O;
• each of Jz and Jv is independently halo, C1-6 aliphatic, C3-6 cycloaliphatic, NO2, CN, NH2, —NH(C1-4 aliphatic), —N(C1-4 aliphatic)2, OH, —O(C1-4 aliphatic), —CO2H, —CO2(C1-4 aliphatic), —O(haloC1-4 aliphatic), or halo(C1-4 aliphatic);
• each of JQ, J4, J23, J24, J67, J26 , and J46 is independently M or —Y-M;
• each Y is independently an unsubstituted C1-6 aliphatic optionally replaced with 0-3 occurrences of —NR—, —O—, —S—, —C(O)—, —SO—, or —SO2—;
• each M is independently H, C1-6 aliphatic, C3-6 cycloaliphatic, halo(C1-4 aliphatic), —O(haloC1-4 aliphatic), 3- to 6-membered heterocyclyl, halo, NO2, CN, OH, OR′, SH, SR′, NH2, NHR′, N(R′)2, COH, COR′, CO2H, CO2R′, CONH2, CONHR′, CONR′2, OCOR′, OCONH2, OCONHR′, OCON(R′)2, NHCOR′, NR′COR′, NHCO2R′, NR′CO2R′, NHCO2H, NR′CO2H, NHCONH2, NHCONHR′, NHCON(R′)2, SO2NH2, SO2NHR′, SO2N(R′)2, NHSO2R′, or NR′SO2R′;
• R is H or unsubstituted C1-6 aliphatic;
• and
• R′ is unsubstituted C1-6 aliphatic;
• or two R′ groups, together with the atom to which they are bound, form an unsubstituted 3- to 8-membered saturated or partially unsaturated monocyclic ring having 0-1 heteroatoms each independently selected from O, N, and S.