5-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(1h-pyrazol-1-yl)pyrazolo[1,5-a]pyrimidine derivatives and related compounds as Trk kinase inhibitors for treating cancer

A compound of formula (IV)

• or a pharmaceutically acceptable salt, hydrate, solvate, isotope, prodrug, stereoisomer, or tautomer thereof, wherein:
• X is H, (C1-C6) alkyl, or halogen;
• X1 is H or D;
• Y is H, D, C1-C6 alkyl, or CN;
• L is
• —O(CR3R4)—(C6-C10) aryl, —NR5—(CR3R4)—(C6-C10) aryl, —O(CR3R4)-5- or 6-membered heteroaryl, or NR5—(CR3R4)-5- or 6-membered heteroaryl, wherein the aryl and heteroaryl are optionally substituted with one or more R6;
• each R1 and R1′ is independently H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, or —OH;
• R2 is (C6-C10) aryl or 5- or 6-membered heteroaryl, wherein the aryl and heteroaryl are optionally substituted with one or more R7;
• R2′ is H, D, (C1-C6) alkyl, or halogen;
• each R3, R4 and R5 at each occurrence is independently H or (C1-C6) alkyl;
• each R6 is independently at each occurrence (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, or halogen;
• each R7 is independently at each occurrence (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, or halogen;
• A is
• Q is N or CR9;
• each of R8 and R9, at each occurrence, independently is H, halogen, cyano, (C0-C6)alkyl-ORa, (C0-C6)alkyl-NRaRb, (C0-C6)alkyl-C(O)Ra, (C0-C6)alkyl-P(O)RaRb, (C0-C6)alkyl-S(O)pRa, NReC(O)Ra, or NReS(O)2Ra, or RW,
• or R8 and R9, together with the atoms to which they are attached, form a 5- to 7-membered ring optionally comprising one or more heteroatoms selected from N, O, and S and optionally substituted with one or more RS1;
• each RW independently is (C1-C6) alkyl, (C1-C6) haloalkyl, (C3-C5) cycloalkyl, 3- to 8-membered heterocycloalkyl, (C6-C10) aryl, or 5 to 10-membered heteroaryl, each of which is optionally substituted with one or more RS2;
• each of RS1 and RS2, at each occurrence, independently is H, halogen, cyano, (C1-C6) alkyl, (C1-C6) haloalkyl, (C0-C3)alkyl-ORc, (C0-C3)alkyl-NRcRd, C(O)ORc, or C(O)NRcRd;
• each of Ra, Rb, Rc, and Rd independently is Ri, (C3-C5) cycloalkyl, 3- to 8-membered heterocycloalkyl, (C0-C3)alkyl-ORg, or (C0-C3)alkyl-NRgNRh,
• or Ra and Rb or Rc and Rd together with the atoms to which they are attached form a 5 to 7-membered ring optionally comprising one or more heteroatoms selected from N, O, and S;
• each of Re, Rf, Rg, Rh, Ri, and Rj independently is H, (C1-C6) alkyl or (C1-C6) haloalkyl;
• n is 0, 1, or 2;
• and
• p is 0, 1, or 2.