# US 11,111,247 B2 · Pyrazolopyrimidine compounds and uses thereof

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- Number: US 11,111,247 B2
- Document ID: US11111247B2
- Status: Granted
- Kind: B2
- Application number: 16/580,766
- Filed: 2019-09-24
- Published: 2020-03-26
- Granted: 2021-09-07
- Earliest claimed: 2018-09-25
- Assignees: Incyte Corporation
- Applicants: Incyte Corporation
- Inventors: Oleg Vechorkin; Minh Nguyen; Chao Qi; Anlai Wang; Liangxing Wu; Wenqing Yao; Peng Zhao
- Web page: https://patentgrep.com/patent/US11111247B2

## CPC

- C07D 487/02: in which the condensed system contains two hetero rings
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61P 35/00: Antineoplastic agents
- C07D 487/04: Ortho-condensed systems
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting ALK2 activity and/or FGFR activity, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with ALK2 activity and/or FGFR activity, such as cancer.

## Claims

### Claim 1

A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from Cy1, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, C(═NRe)Rb, C(═NORa)Rb, C(═NRe)NRcRd, NRcC(═NRe)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd; wherein said C2-6 alkenyl and C2-6 alkynyl are each substituted with 1, 2, 3, or 4 substituents independently selected from R10;
Cy1 is selected from C3-8 cycloalkyl, 4-12 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-12 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C3-8 cycloalkyl, 4-12 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
Cy is 4-12 membered heterocycloalkyl; wherein the 4-12 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; wherein when the 4-12 membered heterocycloalkyl of Cy has a fused aromatic ring, the 4-12 membered heterocycloalkyl is directly attached to the pyrazolopyrimidine core structure through a ring-forming atom of the saturated or partially saturated ring; and wherein the 4-12 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R20;
R2 is selected from H, D, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy and C1-4 haloalkoxy;
each R10 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1 NRc1C(O)NRc1Rd1, C(═NRe1)Rb1, C(═NORa1)Rb1, C(═NRe1)NRc1Rd1, NRc1C(═NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11;
or two R10 substituents taken together with the carbon atom to which they are attached form a spiro 4-7-membered heterocycloalkyl ring, or a spiro C3-6 cycloalkyl ring; wherein each spiro 4-7-membered heterocycloalkyl ring has at least one ring-forming carbon atom and 1, 2 or 3, ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of each spiro 4-7-membered heterocycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the spiro 4-7-membered heterocycloalkyl ring and spiro C3-6 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
each R11 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, NRc3Rd3 NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3 S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R12;
each R12 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5 S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each R20 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(═NRe2)Rb2, C(═NORa2)Rb2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2 S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21;
each R21 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4 S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, and S(O)2NRc4Rd4; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R22;
each R22 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, 5-6 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6Rd6 NRc6C(O)Rb6, NR6C(O)ORa6 NRc6S(O)Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6 S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, and S(O)2NRc6Rd6; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Ra, Rc, and Rd is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R10;
or any Rc and Rd attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
each Rb is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R10;
each Re is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl)aminosulfonyl;
each Ra1, Rc1 and Rd1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11;
or any Rc1 and Rd1 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
each Rb1 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11;
each Re1 is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, aminosulfonyl, and di(C1-6 alkyl)aminosulfonyl;
each Ra2, Rc2 and Rd2 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21;
or any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R21;
each Rb2 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21;
each Re2 is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, aminosulfonyl, and di(C1-6 alkyl)aminosulfonyl;
each Ra3, Rc3 and Rd3 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C13 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R12;
or any Rc3 and Rd3 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R12;
each Rb3 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R12;
each Ra4, Rc4 and Rd4 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R22;
or any Rc4 and Rd4 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R22;
each Rb4 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R22;
each Ra5, Rc5 and Rd5 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
or any Rc5 and Rd5 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from Rg;
each Rb5 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Ra6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
or any Rc6 and Rd6 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from Rg;
each Rb6 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg; and
each Rg is independently selected from OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-2 alkylene, C1-6 alkoxy, C1-6 haloalkoxy, C1-3 alkoxy-C1-3 alkyl, C1-3 alkoxy-C1-3 alkoxy, HO—C1-3 alkoxy, HO—C1-3 alkyl, cyano-C1-3 alkyl, H2N—C1-3 alkyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R1 is selected from Cy1, C1-6 haloalkyl, halo, CN, ORa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, NRcRd, and NRcC(O)Rb.

### Claim 3 (depends on 1)

The compound of claim 1, wherein R1 is Cy1.

### Claim 4 (depends on 1)

The compound of claim 1, wherein Cy1 is selected from C6-10 aryl and 5-10 membered heteroaryl; wherein the 5-10 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2 or 3 substituents independently selected from R10.

### Claim 5 (depends on 1)

The compound of claim 1, wherein Cy1 is C6-10 aryl optionally substituted with 1 or 2 substituents independently selected from R10.

### Claim 6 (depends on 1)

The compound of claim 1, wherein Cy1 is phenyl optionally substituted with 1 or 2 substituents independently selected from R10.

### Claim 7 (depends on 1)

The compound of claim 1, wherein Cy1 is 5-10 membered heteroaryl; wherein the 5-10 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the 5-10 membered heteroaryl is optionally substituted with 1 or 2 substituents independently selected from R10.

### Claim 8 (depends on 1)

The compound of claim 1, wherein Cy1 is 5-6 membered heteroaryl; wherein the 5-6 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-6 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the 5-6 membered heteroaryl is optionally substituted with 1 or 2 substituents independently selected from R10.

### Claim 9 (depends on 1)

The compound of claim 1, wherein Cy1 is pyridinyl optionally substituted with 1 or 2 substituents independently selected from R10.

### Claim 10 (depends on 1)

The compound of claim 1, wherein Cy1 is selected from pyrazolyl, phenyl and pyridinyl, wherein the pyrazolyl, phenyl and pyridinyl are each optionally substituted with 1 or 2 substituents independently selected from R10.

### Claim 11 (depends on 1)

The compound of claim 1, wherein R10 is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, ORa1, 4-10 membered heterocycloalkyl-C1-3 alkylene, 5-6 membered heteroaryl-C1-3 alkylene, and C(O)NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1 or 2 substituents independently selected from RH.

### Claim 12 (depends on 1)

The compound of claim 1, wherein R10 is selected from C1-6 alkyl, halo, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl-C1-3 alkylene, 5-6 membered heteroaryl-C1-3 alkylene, and C(O)NRc1Rd1; wherein said C1-6 alkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene, are each optionally substituted with 1 or 2 substituents independently selected from R11.

### Claim 13 (depends on 1)

The compound of claim 1, wherein R10 is 4-10 membered heterocycloalkyl optionally substituted with 1 or 2 substituents independently selected from RH.

### Claim 14 (depends on 1)

The compound of claim 1, wherein R10 is 5-6 membered heterocycloalkyl optionally substituted with 1 or 2 substituents independently selected from R11.

### Claim 15 (depends on 1)

The compound of claim 1, wherein R10 is piperazinyl optionally substituted with 1 or 2 substituents independently selected from R11.

### Claim 16 (depends on 1)

The compound of claim 1, wherein R10 is selected from methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, fluoro, methylcarbamoyl, phenyl, piperazinyl, pyrrolidinyl, morpholino, piperidinyl, pyridinyl, hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl, tetrahydropyranyl, cyclohexyl, 2-morpholinoethyl, pyridinylmethyl, 2,2,2-trifluoroethyl, and imidazo[1,2-a]pyridin-6-yl; wherein said methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, methylcarbamoyl, phenyl, piperazinyl, pyrrolidinyl, morpholino, piperidinyl, pyridinyl, hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl, tetrahydropyranyl, cyclohexyl, 2-morpholinoethyl, pyridinylmethyl, 2,2,2-trifluoroethyl, and imidazo[1,2-a]pyridin-6-yl are each optionally substituted with 1 or 2 substituents independently selected from R11.

### Claim 17 (depends on 1)

The compound of claim 1, wherein R11 is independently selected from C1-6 alkyl, C1-6 haloalkyl, halo, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, CN, ORa3, C(O)NRc3Rd3, C(O)Rb3, and NRc3Rd3, wherein said C1-6 alkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R12.

### Claim 18 (depends on 1)

The compound of claim 1, wherein R11 is independently selected from C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl.

### Claim 19 (depends on 1)

The compound of claim 1, wherein R11 is C1-6 alkyl.

### Claim 20 (depends on 1)

The compound of claim 1, wherein R11 is methyl.

### Claim 21 (depends on 1)

The compound of claim 1, wherein R10 is methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, fluoro, 4-methylpiperazin-1-yl, 4-ethylpiperazin-1-yl, methylcarbamoyl, 1-methylpyrrolidin-3-yl, 1-(2-hydroxyethyl)pyrrolidin-3-yl, 4-(1-hydroxypropan-2-yl)piperazin-1-yl, 4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl, 4-(2-carboxypropan-2-yl)piperazin-1-yl, 2-methylmorpholino, 3,4-dimethylpiperazin-1-yl, 4-hydroxypiperidin-1-yl, 7-hydroxyhexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl, 2-methoxyethyl, tetrahydro-2H-pyran-4-yl, 4-hydroxycyclohexyl, 1-(dimethylcarbamoyl)piperidin-4-yl, 1-isobutyrylpiperidin-4-yl, 2-morpholinoethyl, 4-methylpiperazin-1-yl, pyridin-4-ylmethyl, 2,2,2-trifluoroethyl, pyridin-4-yl, pyridin-3-yl, 4-cyanophenyl, 2-methylpyridin-4-yl, 6-(dimethylamino)pyridin-3-yl, 5-cyanopyridin-3-yl, 6-cyanopyridin-3-yl, 4-cyano-3-methylphenyl, 4-cyano-2-methylphenyl, 4-cyano-3-fluorophenyl, 4-(methylcarbamoyl)phenyl, 4-(dimethylcarbamoyl)phenyl, 3-fluoro-4-(methylcarbamoyl)phenyl, 3-(6-(methylcarbamoyl)pyridin-3-yl, 3-methylpiperazin-1-yl or 4-methylpiperazin-1-yl.

### Claim 22 (depends on 1)

The compound of claim 1, wherein R2 is H.

### Claim 23 (depends on 1)

The compound of claim 1, wherein Cy is 4-8 membered heterocycloalkyl; wherein the 4-8 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 4-8 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; wherein when the 4-8 membered heterocycloalkyl of Cy has a fused aromatic ring, the 4-8 membered heterocycloalkyl is directly attached to the pyrazolopyrimidine core structure through a ring-forming atom of the saturated or partially saturated ring; and wherein the 4-8 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R20.

### Claim 24 (depends on 1)

The compound of claim 1, wherein R20 is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, and NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R21.

### Claim 25 (depends on 1)

The compound of claim 1, wherein R20 is selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C6-10 aryl, halo, CN, ORa2, C(O)Rb2, C(O)NRc2Rd2, and C(O)ORa2; wherein said C1-6 alkyl, C3-10 cycloalkyl, and C6-10 aryl are each optionally substituted with 1 or 2 substituents independently selected from R21.

### Claim 26 (depends on 1)

The compound of claim 1, wherein each R20 is C1-6 alkyl optionally substituted with 1 or 2 substituents independently selected from R21.

### Claim 27 (depends on 1)

The compound of claim 1, wherein R20 is C6-10 aryl optionally substituted with 1 or 2 substituents independently selected from R21.

### Claim 28 (depends on 1)

The compound of claim 1, wherein R20 is selected from ORa2, C(O)Rb2, C(O)NRc2Rd2, and C(O)ORa2.

### Claim 29 (depends on 1)

The compound of claim 1, wherein R21 is selected from halo, CN, and ORa4.

### Claim 30 (depends on 1)

The compound of claim 1, wherein each Ra2, Rc2 and Rd2 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1 or 2 substituents independently selected from R21.

### Claim 31 (depends on 1)

The compound of claim 1, wherein each Ra2, Rc2 and Rd2 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R21.

### Claim 32 (depends on 1)

The compound of claim 1, wherein any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from R21.

### Claim 33 (depends on 1)

The compound of claim 1, wherein Rb2 is selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl; wherein said C1-6 alkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R21.

### Claim 34 (depends on 1)

The compound of claim 1, wherein each Ra4, Rc4 and Rd4 is independently selected from H and C1-6 alkyl.

### Claim 35 (depends on 1)

The compound of claim 1, wherein each Ra4, Rc4 and Rd4 is independently C1-6 alkyl.

### Claim 36 (depends on 1)

The compound of claim 1, wherein Cy is piperidinyl, morpholinyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.2.1]octanyl, piperazinyl, diazabicyclo[3.2.1]octanyl, 1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl, 5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl, 2,5-diazabicyclo[2.2.2]octan-2-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 3-oxopiperazinyl, 5,6,7,8-tetrahydro-1,6-naphthyridin-6-yl, 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazin-7-yl, 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-5-yl, 1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl, 1,4,5,6,7,8-hexahydro-5,8-epiminocyclohepta[c]pyrazol-9-yl, or 2-oxo-3,8-diazabicyclo[3.2.1]octan-8-yl, each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R20.

### Claim 37 (depends on 1)

The compound of claim 1, wherein Cy is

### Claim 38 (depends on 1)

The compound of claim 1, wherein the compound is a compound of Formula II:
or a pharmaceutically acceptable salt thereof.

### Claim 39 (depends on 1)

The compound of claim 1, wherein the compound is a compound of Formula III:
or a pharmaceutically acceptable salt thereof.

### Claim 40 (depends on 1)

The compound of claim 1, wherein the compound is a compound of Formula IV:
or a pharmaceutically acceptable salt thereof.

### Claim 41 (depends on 1)

The compound of claim 1, wherein the compound is a compound of Formula V:
or a pharmaceutically acceptable salt thereof.

### Claim 42 (depends on 1)

The compound of claim 1, wherein:
R1 is Cy1;
Cy1 is selected from C5-6 cycloalkyl, 5-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; wherein the 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-6 membered heteroaryl and 5-6 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C5-6 cycloalkyl, 5-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
Cy is 4-12 membered heterocycloalkyl; wherein the 4-12 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; wherein when the 4-12 membered heterocycloalkyl of Cy has a fused aromatic ring, the 4-12 membered heterocycloalkyl is directly attached to the pyrazolopyrimidine core structure through a ring-forming atom of the saturated or partially saturated ring; and wherein the 4-12 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R20;
R2 is selected from H, D, C1-4 alkyl and C1-4 haloalkyl;
each R10 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, and NRc1Rd1, NRc1C(O)Rb1; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1 or 2 substituents independently selected from R11;
each R11 is independently selected from C1-6 alkyl, C1-6 haloalkyl, halo, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, CN, ORa3, C(O)NRc3Rd3, C(O)Rb3, and NRc3Rd3, wherein said C1-6 alkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R12;
each R12 is independently selected from C1-6 alkyl, C1-6 haloalkyl, halo, CN, ORa5, and C(O)ORa5;
each R20 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, and NRc2C(O)ORa2; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each R21 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, and ORa4;
each Ra1, Rc1 and Rd1 is independently selected from H, and C1-6 alkyl;
or any Rc1 and Rd1 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
each Rb1 is independently selected from C1-6 alkyl;
each Ra2, Rc2 and Rd2 is independently selected from H, C1-6 alkyl and C1-6 haloalkyl;
wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R21;
or any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R21;
each Rb2 is independently selected from C1-6 alkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl; wherein said C1-6 alkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each Ra3, Rc3 and Rd3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R12;
or any Rc3 and Rd3 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R12;
each Rb3 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R′2;
each Ra4 is independently selected from H, and C1-6 alkyl; and
each Ra5 is independently selected from H, and C1-6 alkyl.

### Claim 43 (depends on 1)

The compound of claim 1, wherein:
R1 is Cy1;
Cy1 is selected from phenyl and 5-6 membered heteroaryl; wherein the 5-6 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-6 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R10;
Cy is 4-12 membered heterocycloalkyl; wherein the 4-12 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; wherein when the 4-12 membered heterocycloalkyl of Cy has a fused aromatic ring, the 4-12 membered heterocycloalkyl is directly attached to the pyrazolopyrimidine core structure through a ring-forming atom of the saturated or partially saturated ring; and wherein the 4-12 membered heterocycloalkyl is optionally substituted with 1,2 or 3 substituents independently selected from R20;
R2 is H or D;
each R10 is independently selected from C1-6 alkyl, halo, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl-C1-3 alkylene, 5-6 membered heteroaryl-C1-3 alkylene, and C(O)NRc1Rd1; wherein said C1-6 alkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1 or 2 substituents independently selected from R11;
each R11 is independently selected from C1-6 alkyl, C1-6 haloalkyl, halo, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, CN, ORa3, C(O)NRc3Rd3, C(O)Rb3, and NRc3Rd3, wherein said C1-6 alkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R12;
each Rc1 and Rd1 is independently selected from H, and C1-6 alkyl;
each Ra3, Rb3, Rc3 and Rd3 is independently selected from H, and C1-6 alkyl;
each R12 is independently selected from C1-6 alkyl, C(O)OH, and OH;
each R20 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C6-10 aryl, halo, CN, ORa2, C(O)Rb2, C(O)NRc2Rd2, and C(O)ORa2; wherein said C1-6 alkyl, C3-10 cycloalkyl, and C6-10 aryl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each Ra2, Rc2 and Rd2 is independently selected from H, C1-6 alkyl and C1-6 haloalkyl; wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R21;
or any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from R21;
each Rb2 is independently selected from C1-6 alkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl; wherein said C1-6 alkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each R21 is independently selected from halo, D, CN, and ORa4; and
each Ra4 is C1-6 alkyl.

### Claim 44 (depends on 1)

The compound of claim 1, wherein the compound is a compound of Formula V:
or a pharmaceutically acceptable salt thereof, wherein:
Cy is 4-12 membered heterocycloalkyl; wherein the 4-12 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; wherein when the 4-12 membered heterocycloalkyl of Cy has a fused aromatic ring, the 4-12 membered heterocycloalkyl is directly attached to the pyrazolopyrimidine core structure through a ring-forming atom of the saturated or partially saturated ring; and wherein the 4-12 membered heterocycloalkyl is optionally substituted with 1, 2 or 3 substituents independently selected from R20;
R10 is selected from C1-6 alkyl, halo, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl-C1-3 alkylene, 5-6 membered heteroaryl-C1-3 alkylene, and C(O)NRc1Rd1; wherein said C1-6 alkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1 or 2 substituents independently selected from R11;
each R11 is independently selected from C1-6 alkyl, C1-6 haloalkyl, halo, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, CN, ORa3, C(O)NRc3Rd3, C(O)Rb3, and NRc3Rd3, wherein said C1-6 alkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R12;
each Rc1 and Rd1 is independently selected from H, and C1-6 alkyl;
each Ra3, Rb3, Rc3 and Rd3 is independently selected from H, and C1-6 alkyl;
each R12 is independently selected from C1-6 alkyl, C(O)OH, and OH;
each R20 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C6-10 aryl, halo, CN, ORa2, C(O)Rb2, C(O)NRc2Rd2, and C(O)ORa2; wherein said C1-6 alkyl, C3-10 cycloalkyl, and C6-10 aryl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each Ra2, Rc2 and Rd2 is independently selected from H, C1-6 alkyl and C1-6 haloalkyl;
wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R21;
or any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from R21;
each Rb2 is independently selected from C1-6 alkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl; wherein said C1-6 alkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each R21 is independently selected from halo, D, CN, and ORa4; and
each Ra4 is C1-6 alkyl.

### Claim 45 (depends on 1)

The compound of claim 1, wherein the compound is a compound of Formula VI, or a pharmaceutically acceptable salt thereof:
wherein:
X is selected from CH, CF, CCH3 and N;
Cy is 4-12 membered heterocycloalkyl; wherein the 4-12 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; wherein when the 4-12 membered heterocycloalkyl of Cy has a fused aromatic ring, the 4-12 membered heterocycloalkyl is directly attached to the pyrazolopyrimidine core structure through a ring-forming atom of the saturated or partially saturated ring; and wherein the 4-12 membered heterocycloalkyl is optionally substituted with 1, 2 or 3 substituents independently selected from R20;
R10 is selected from 4-10 membered heterocycloalkyl, wherein said 4-10 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from R11;
each R11 is independently selected from C1-6 alkyl, and 4-10 membered heterocycloalkyl, C1-6 alkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R12;
each R12 is independently selected from C1-6 alkyl, C(O)OH, and OH;
each R20 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C6-10 aryl, halo, CN, ORa2, C(O)Rb2, C(O)NRc2Rd2, and C(O)ORa2; wherein said C1-6 alkyl, C3-10 cycloalkyl, and C6-10 aryl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each Ra2, Rc2 and Rd2 is independently selected from H, C1-6 alkyl and C1-6 haloalkyl;
wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R21;
or any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from R21;
each Rb2 is independently selected from C1-6 alkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl; wherein said C1-6 alkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each R21 is independently selected from halo, D, CN, and ORa4; and
each Ra4 is C1-6 alkyl.

### Claim 46 (depends on 1)

The compound of claim 1, wherein the compound is selected from:
5-((2R,6S)-2,6-dimethylpiperidin-1-yl)-3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidine;
(3R,5S)-3, 5-dimethyl-4-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)morpholine;
5-(7-azabicyclo[2.2.1]heptan-7-yl)-3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidine;
(1R,5S,6S)-8-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octan-6-o1;
1-((3R,5S)-3, 5-dimethyl-4-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-1-yl)-2-methylpropan-1-one;
1-((3R,5S)-3, 5-dimethyl-4-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-1-yl)-2-methoxyethan-1-one;
(3R,5S)-N-isopropyl-3,5-dimethyl-4-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxamide;
(3R,5S)-N,N,3,5-tetramethyl-4-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxamide;
((3R,5S)-3, 5-dimethyl-4-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-1-yl)(pyrrolidin-1-yl)methanone;
((3R,5S)-3, 5-dimethyl-4-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-1-yl)(3-fluoropyrrolidin-1-yl)methanone;
Ethyl (3R,5S)-3,5-dimethyl-4-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxylate;
2-Fluoroethyl (3R,5S)-3,5-dimethyl-4-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxylate;
Cyclopropyl((1R,5S)-8-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methanone;
((1R,5S)-8-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3, 8-diazabicyclo[3.2.1]octan-3-yl)(pyrrolidin-1-yl)methanone;
4-((1R,5S)-8-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)benzonitrile; and
5-((2R,6S)-2,6-dimethylpiperidin-1-yl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidine,
or a pharmaceutically acceptable salt thereof.

### Claim 47 (depends on 1)

The compound of claim 1, wherein the compound is selected from:
Methyl (3R,5S)-3,5-dimethyl-4-(3-(6-((R)-3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxylate;
(R)-5-(1-Methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)-3-(6-(3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidine;
(R)-5-(3-Methyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-3-(6-(3-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidine;
(5-(3-(6-((R)-3-Methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2,5-diazabicyclo[2.2.2]octan-2-yl)(pyrrolidin-1-yl)methanone;
((1S,4S)-5-(3-(6-((R)-3-Methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)(pyrrolidin-1-yl)methanone
Methyl (3R,5S)-3,5-dimethyl-4-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxylate;
Methyl (3R,5S)-4-(3-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,5-dimethylpiperazine-1-carboxylate;
Methyl (3R,5S)-3,5-dimethyl-4-(3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxylate;
Methyl (3R,5S)-4-(3-(4-(4-ethylpiperazin-1-yl)-3-methylphenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,5-dimethylpiperazine-1-carboxylate;
Methyl (3R,5S)-3,5-dimethyl-4-(3-(4-(methylcarbamoyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxylate;
Methyl (3R,5S)-3,5-dimethyl-4-(3-(4-(1-methylpyrrolidin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxylate;
Methyl (3R,5S)-4-(3-(4-(1-(2-hydroxyethyl)pyrrolidin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,5-dimethylpiperazine-1-carboxylate;
Methyl (3R,5S)-4-(3-(4-(4-(1-hydroxypropan-2-yl)piperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,5-dimethylpiperazine-1-carboxylate;
Methyl (3R,5S)-3,5-dimethyl-4-(3-(4-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxylate;
2-(4-(4-(5-((2R,6S)-4-(Methoxycarbonyl)-2,6-dimethylpiperazin-1-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-2-methylpropanoic acid;
Methyl (3R,5S)-3,5-dimethyl-4-(3-(6-((R)-2-methylmorpholino)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazine-1-carboxylate;
Methyl (3R,5S)-4-(3-(6-((R)-3,4-dimethylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,5-dimethylpiperazine-1-carboxylate;
Methyl (3R,5S)-4-(3-(4-(4-hydroxypiperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,5-dimethylpiperazine-1-carboxylate;
Methyl (3R,5S)-4-(3-(4-((7S,8aR)-7-hydroxyhexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,5-dimethylpiperazine-1-carboxylate;
1-Methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-2-one;
1-Cyclopropyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-2-one;
1,3-Dimethyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-2-one;
3-Ethyl-1-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-2-one;
6-(3-(1-Methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine;
3-(1-Methyl-1H-pyrazol-4-yl)-5-(1-(trifluoromethyl)-5, 6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)-1H-pyrazolo[4,3-d]pyrimidine;
5-(3-(1-Methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine;
3-(1-Methyl-1H-pyrazol-4-yl)-5-(8-methyl-5, 6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-1H-pyrazolo[4,3-d]pyrimidine;
3-(1-Methyl-1H-pyrazol-4-yl)-5-(1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)-1H-pyrazolo[4,3-d]pyrimidine;
9-(3-(1-Methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-1,4,5,6,7,8-hexahydro-4,7-epiminocyclohepta[c]pyrazole;
1-(2,2-Difluoroethyl)-3-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-2-one;
1-Isopropyl-3-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-2-one;
1-(2-Methoxyethyl)-3-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)piperazin-2-one;
3-Methyl-8-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
3-Ethyl-8-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
3-(2-Fluoroethyl)-8-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
3-Isopropyl-8-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3, 8-diazabicyclo[3.2.1]octan-2-one;
8-(3-(1-(2-Methoxyethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one;
3-Methyl-8-(3-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
8-(3-(1-((1r,4S)-4-Hydroxycyclohexyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one;
N,N-Dimethyl-4-(4-(5-(3-methyl-2-oxo-3,8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxamide;
8-(3-(1-(1-Isobutyrylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-methyl-3, 8-diazabicyclo[3.2.1]octan-2-one;
3-Methyl-8-(3-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
3-Methyl-8-(3-(1-(pyridin-4-ylmethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
3-Methyl-8-(3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
8-(3-(1-Ethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-methyl-3, 8-diazabicyclo[3.2.1]octan-2-one;
8-(3-(1-Isopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-methyl-3, 8-diazabicyclo[3.2.1]octan-2-one;
8-(3-(1-Cyclobutyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-methyl-3, 8-diazabicyclo[3.2.1]octan-2-one;
8-(3-(1-Cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-methyl-3, 8-diazabicyclo[3.2.1]octan-2-one;
3-Methyl-8-(3-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
3-Methyl-8-(3-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
3-Methyl-8-(3-(1-(pyridin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
4-(4-(5-(3-Methyl-2-oxo-3, 8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)benzonitrile;
3-Methyl-8-(3-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3,8-diazabicyclo[3.2.1]octan-2-one;
8-(3-(1-(6-(Dimethylamino)pyridin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one;
5-(4-(5-(3-Methyl-2-oxo-3, 8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)nicotinonitrile;
5-(4-(5-(3-Methyl-2-oxo-3, 8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)picolinonitrile;
8-(3-(1-(Imidazo[1,2-a]pyridin-6-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-methyl-3, 8-diazabicyclo[3.2.1]octan-2-one;
2-Methyl-4-(4-(5-(3-methyl-2-oxo-3, 8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)benzonitrile;
3-Methyl-4-(4-(5-(3-methyl-2-oxo-3, 8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)benzonitrile;
2-Fluoro-4-(4-(5-(3-methyl-2-oxo-3, 8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)benzonitrile;
N,N-Dimethyl-4-(4-(5-(3-methyl-2-oxo-3,8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)benzamide;
N-Methyl-4-(4-(5-(3-methyl-2-oxo-3,8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)benzamide;
2-Fluoro-N-methyl-4-(4-(5-(3-methyl-2-oxo-3,8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)benzamide; and
N-Methyl-5-(4-(5-(3-methyl-2-oxo-3,8-diazabicyclo[3.2.1]octan-8-yl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1H-pyrazol-1-yl)picolinamide;
or a pharmaceutically acceptable salt thereof.

### Claim 48 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.