Pyrazolo[1,5-a]pyrimidines useful as inhibitors of protein kinases

A compound of formula I′:

• or a pharmaceutically accepted salt thereof, wherein
• R is —(C=Q)R2a, CN, or Y;
• wherein
• Y is a 5-10 membered monocyclic or bicyclic heterocyclyl, aryl, or heteroaryl ring;
• each Y is independently and optionally substituted with 0-5 JY;
• Q is O, NH, NR′, or S;
• R′ is C1-6alkyl optionally substituted with 0-4 occurrences of halo, C1-6aliphatic, NO2, NH2, —N(C1-6alkyl), —N(C1-6alkyl)2, SH, —S(C1-6alkyl), OH, —O(C1-6alkyl), —C(O)(C1-6alkyl), —C(O)NH2, —C(O)N(C1-6alkyl), or —C(O)N(C1-6alkyl)2;
• R2a is C1-6aliphatic, C6-10aryl, 5-10 membered heteroaryl, 5-10 membered heterocyclyl, OR5, or N(R5)2;
• each R2a a is independently and optionally substituted with 0-5 J2a;
• R1 is H, —C(O)(C1-6alkyl), —C(O)O(C1-6alkyl), —C(O)NH2, —C(O)N(C1-6alkyl), —C(O)N(C1-6alkyl)2;
• or C1-6 aliphatic;
• each R1 is optionally substituted with 0-4 occurrences of halo, C1-6haloalkyl, C1-6aliphatic, NO2, NH2, —N(C1-6alkyl), —N(C1-6alkyl)2, SH, —S(C1-6alkyl), OH, or —O(C1-6alkyl);
• which they are attached optionally join to form a 5-10 membered carbocyclic or heterocyclic ring;
• wherein said ring is optionally substituted with 0-4 J′;
• R6 is H, C1-6alkoxy, C1-4haloalkyl, C0-6alkyl-heterocyclyl, C0-6alkyl-heteroaryl, C0-6alkyl-aryl, C0-6alkyl-cycloaliphatic, or C1-6 aliphatic wherein up to two methylene units of the aliphatic chain are optionally and independently replaced by a heteroatom selected from O, N, or S in a chemically stable arrangement;
• each R6 is independently and optionally substituted with 0-5 JR6;
• or two R6 groups taken together with the atom to which they are attached optionally join to form a 5-10 membered carbocyclic or heterocyclic ring;
• wherein said ring is optionally substituted with 0-4 J″;
• R8 is halogen, C1-4haloalkyl, phenyl, 5-8 membered heterocyclyl, 5-6 membered heteroaryl, —OR6, —N(R6)2, —SR6, NO2, CN, —COOR6, —C(O)N(R6)2, —SO2R6, —SO2N(R6)2, —NR6C(O)R6, —C(O)R6, —OC(O)R6, —NR6C(O)O—R6, —NR6SO2—R6, —C(O)NR6N(R6)2, —NR6C(O)N(R6)2, —OC(O)N(R6)2, —NR6N(R6)2, —NR6SO2N(R6)2 or C1-12 aliphatic, wherein up to three methylene units of the aliphatic chain can be optionally interrupted with —C(O)R6, —C(O)O—, —OC(O)—, —C(O)—, —C(O)N(R6)—, —NR6CO(R6)—, —O—, —NR6—, or —S—;
• each R8 is independently and optionally substituted with 0-5 JR8;
• each JY, J2a, Ju, JR5, JR6, JR8, J′ and J″ is independently selected from N(R9)2, SR9, OR9, halo, CN, NO2, COOR9, C(O)R9, SO2R9, SOR9, —X—CF3, —X—SH, —X—OH, C1-4haloalkyl, C6-10 aryl, —X—(C6-10 aryl), 5-10 membered heteroaryl, —X-(5-10 membered heteroaryl), C3-10 cycloaliphatic, —X—(C3-10 cycloaliphatic), 5-10 membered heterocyclyl, —X-(5-10 membered heterocyclyl), or X;
• X is C1-12 aliphatic wherein up to two methylene units of the alkylidene chain are optionally and independently replaced by —NH—, —NR″—, —O—, —S—, —CO2—, —OC(O)—, —C(O)CO—, —C(O)—, —C(O)NH—, —C(O)NR″—, —C(═N—CN), —NHCO—, —NR″CO—, —NHC(O)O—, —NR″C(O)O—, —SO2NH—, —SO2NR″—, —NHSO2—, —NR″SO2—, —NHC(O)NH—, —NR″C(O)NH—, —NHC(O)NR″—, —NR″C(O)NR″, —OC(O)NH—, —OC(O)NR″—, —NHNH—, —NHNR″—, —NR″NR″—, —NR″NH—, —NHSO2NH—, —NR″SO2NH—, —NHSO2NR″—, —NR″SO2NR″—, —SO—, —SO2—, —PO—, —PO2—, or —POR″—;
• in a chemically stable arrangement;
• wherein R″ is H or C1-6 aliphatic;
• each JY, J2a, Ju, JR5, JR6, J′, and J″ is optionally and independently substituted with 0-4 occurrences of N(R9)2, SR9, OR9, halo, CN, NO2, COOR9, C(O)R9, SO2R9, SOR9, —X—CF3, —X—SH, —X—OH, C1-4haloalkyl, C6-10 aryl, —X—(C6-10 aryl), 5-10 membered heteroaryl, —X-(5-10 membered heteroaryl), C3-10 cycloaliphatic, —X—(C3-10 cycloaliphatic), 5-10 membered heterocyclyl, —X-(5-10 membered heterocyclyl), or X;
• R9 is H, C1-6 aliphatic, C1-4haloalkyl, C6-10 aryl, —X—(C6-10 aryl), 5-10 membered heteroaryl, —X-(5-10 membered heteroaryl), C3-10 cycloaliphatic, —X—(C3-10 cycloaliphatic), 5-10 membered heterocyclyl, —X-(5-10 membered heterocyclyl) or X, or wherein two R9, taken together with the atom to which they are attached, form a 5-10 membered heterocyclyl, wherein said heterocyclyl is optionally substituted with 0-4 occurrences of halo, CN, NO2, —COOH, —COO(C1-6alkyl), —C(O)H, SO2H, SO2(C1-6alkyl), C1-6haloaliphatic, NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, SH, —S(C1-6alkyl), OH, —O(C1-6alkyl), —C(O)(C1-6alkyl), —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), or —C(O)N(C1-6alkyl)2, C1-4haloalkyl, C6-10 aryl, —X—(C6-10 aryl), 5-10 membered heteroaryl, —X-(5-10 membered heteroaryl), C3-10 cycloaliphatic, —X—(C3-10 cycloaliphatic), 5-10 membered heterocyclyl, —X-(5-10 membered heterocyclyl), or X.