Pyrazolopyridine kinase inhibitors

A compound represented by the following structural formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• T is —CH2—, —CH(Jb)-, —C(Jb)2-, —NH— or —N(Jb)-;
• t is 0, 1, or 2;
• w is 0 or 1;
• each Jc is independently CN, F, Cl, —OR, —CH2OR, or CF3;
• U is Z or Jb
• Z is Y2-Q2;
• Y2 is absent or C1-6 alkyl optionally and independently substituted with one or more Jd;
• Q2 is absent or C3-C8 cyloalkyl having 0-1 heteroatoms optionally and independently substituted with one or more Je;
• wherein Y2 and Q2 are not both absent;
• each Jb is independently —F, —OR, —CN, —CF3, —N(R)2, —C(O)N(R)2, C1-6 alkyl optionally and independently substituted with one or more Ja;
• each Ja is independently —F, —OR, —N(R)2, or —C(O)N(R)2;
• each Jd is independently —OR, —CN, —C(O)N(R)2, —N(R)2 or F;
• each Je is independently —OR, CF3, —N(R)2 or F;
• and
• each R is —H or C1-C6 alkyl;
• with the proviso that the compound is not:

A process for making a compound represented by structural formula I:

• wherein:
• T is —NH— or absent;
• each Jc1 and Jc2 is independently —CN, —F, —Cl, —OR, —CH2OR, or —CF3;
• each U1, U2, and U3 is independently —H, Z, or Jb wherein no more than one of U1, U2, and U3 is —H;
• or two of U1, U2, and U3 join together to form a C1-C6 cyloalkyl ring having 0-1 heteroatoms independently substituted with one or more Je;
• Z is Y2-Q2;
• Y2 is absent or C1-6 alkyl optionally and independently substituted with one or more Jd;
• Q2 is absent or C3-C8 cyloalkyl having 0-1 heteroatoms optionally and independently substituted with one or more Je, wherein Y2 and Q2 are not both absent;
• each Jb is independently —F, —OR, —CN, —CF3, —N(R)2, —C(O)N(R)2, C1-6 alkyl optionally and independently substituted with one or more Ja;
• each Ja is independently —F, —OR, —N(R)2, or —C(O)N(R)2;
• each Jd is independently —OR, —CN, —C(O)N(R)2, —N(R)2 or F;
• each Je is independently C1-C6 alkyl, —OR, —N(R)2CF3, or F;
• each R is —H or C1-C6 alkyl;
• and
• wherein there is a chiral center at the carbon indicated by *;
• and
• wherein (S) represents stereochemistry on the ring carbon,
• with the proviso that the compound is not:
• comprising the steps of:
• a) combining amide A with G to form C;
• b) heating C in the presence of hydrazine to form D;
• and
• c) displacing the halogen on D with an amine J to form I.

A process for making a compound represented by structural formula I:

• wherein:
• T is —NH— or absent;
• each Jc1 and Jc2 is independently —CN, —F, —Cl, —OR, —CH2OR, or —CF3;
• each U1, U2, and U3 is independently —H, Z, or Jb wherein no more than one of U1, U2, and U3 is —H;
• or two of U1, U2, and U3 join together to form a C1-C6 cyloalkyl ring having 0-1 heteroatoms independently substituted with one or more Je;
• Z is Y2-Q2;
• Y2 is absent or C1-6 alkyl optionally and independently substituted with one or more Jd;
• Q2 is absent or C3-C8 cyloalkyl having 0-1 heteroatoms optionally and independently substituted with one or more Je, wherein Y2 and Q2 are not both absent;
• each Jb is independently —F, —OR, —CN, —CF3, —N(R)2, —C(O)N(R)2, C1-6 alkyl optionally and independently substituted with one or more Ja;
• each Ja is independently —F, —OR, —N(R)2, or —C(O)N(R)2;
• each Jd is independently —OR, —CN, —C(O)N(R)2, —N(R)2 or F;
• each Je is independently C1-C6 alkyl, —OR, —N(R)2 CF3, or F;
• each R is —H or C1-C6 alkyl;
• Pr is a protecting group;
• and
• wherein there is a chiral center at the carbon indicated by *;
• and
• wherein (S) represents stereochemistry on the ring carbon, with the proviso that the compound is not:
• comprising the steps of:
• a) combining L with M to form N;
• and
• b) displacing the halogen on N with an amine J to form I.

A process for making a compound represented by structural formula I:

• wherein:
• T is —NH— or absent;
• each Jel and Jc2 is independently —CN, —F, —Cl, —OR, —CH2OR, or —CF3;
• each U1, U2, and U3 is independently —H, Z, or Jb wherein no more than one of U1, U2, and U3 is —H;
• or two of U1, U2, and U3 join together to form a C1-C6 cyloalkyl ring having 0-1 heteroatoms independently substituted with one or more Je;
• Z is Y2-Q2;
• Y2 is absent or C1-6 alkyl optionally and independently substituted with one or more Jd;
• Q2 is absent or C3-C8 cyloalkyl having 0-1 heteroatoms optionally and independently substituted with one or more Je, wherein Y2 and Q2 are not both absent;
• each Jb is independently —F, —OR, —CN, —CF3, —N(R)2, —C(O)N(R)2, C1-6 alkyl optionally and independently substituted with one or more Ja;
• each Ja is independently —F, —OR, —N(R)2, or —C(O)N(R)2;
• each Jd is independently —OR, —CN, —C(O)N(R)2, —N(R)2 or F;
• each Je is independently C1-C6 alkyl, —OR, —N(R)2 CF3, or F;
• each R is —H or C1-C6 alkyl;
• Pr is a protecting group;
• and
• wherein there is a chiral center at the carbon indicated by *;
• and
• wherein (S) represents stereochemistry on the ring carbon, with the proviso that the compound is not:
• comprising the steps of:
• a) combining J with M to form P;
• b) combining P with L to form Q;
• and
• c) deprotection of Q to form I.