IP Library › Granted Patent US 12,371,435
Granted Patent B2
US 12,371,435 · App. 17/822,667 · Granted Jul 29, 2025

Substituted imidazo[1,2-c]pyrimidines as PRC2 inhibitors

Inventors: Matthew Arnold Marx (San Diego, CA); Matthew Randolph Lee (Del Mar, CA); Thomas P. Bobinski (San Diego, CA); Aaron Craig Burns (San Diego, CA); Nidhi Arora (San Diego, CA); James Gail Christensen (San Diego, CA); John Michael Ketcham (San Diego, CA)
Assignee: MIRATI THERAPEUTICS, INC.
C07D487/04
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Quick Facts
Patent No.
US 12,371,435
App. No.
17/822,667
Granted
Jul 29, 2025
Kind
B2
Abstract

The present invention relates to a process for the preparation of a compound of Formula (G), comprising reacting a compound of Formula (H) with a compound of Formula (D) in the presence of a palladium catalyst to afford the compound of Formula (G).

Claims (98)

1. A process for preparing a compound of Formula (G):

wherein:

R 1 is C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, —NR 5 -heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;

wherein any cycloalkyl or heterocyclyl is optionally substituted with one or more independently selected R 4 substituents;

wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O) C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, and heteroaryl;

wherein each cycloalkyl and heterocyclyl of the aryl or heteroaryl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl of the aryl or heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl;

each R 4 is independently halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , ═O, P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl;

wherein each cycloalkyl and heterocyclyl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl;

each R 7 is independently halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), ═O, cycloalkyl, or heterocyclyl;

each R 3 is independently H, halogen, or C 1-3 alkyl;

R 6 is H, halogen, C 1-3 alkyl, haloalkyl, hydroxyalkyl, or heteroalkyl;

X is —CR 5 R 5 —, —CR 5 OH—, or —O—; and

each R 5 is independently H or C 1-3 alkyl;

wherein the process comprises the following step:

reacting a compound of Formula (H):

wherein:

each R 3 is independently H, halogen, or C 1-3 alkyl;

R 6 is H, halogen, C 1-3 alkyl, haloalkyl, hydroxyalkyl, or heteroalkyl;

X is —CR 5 R 5 —, —CR 5 OH—, or —O—; and

each R 5 is independently H or C 1-3 alkyl;

with a compound of Formula (D):

Y—R 1    (D)

wherein:

R 1 is C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, —NR 5 -heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;

wherein any cycloalkyl or heterocyclyl is optionally substituted with one or more independently selected R 4 substituents;

wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, and heteroaryl;

wherein each cycloalkyl and heterocyclyl of the aryl or heteroaryl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl of the aryl or heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl;

each R 4 is independently halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , ═O, P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl;

wherein each cycloalkyl and heterocyclyl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl;

each R 7 is independently halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), ═O, cycloalkyl, or heterocyclyl;

each R 5 is independently H or C 1-3 alkyl; and

Y is a boronic acid;

in the presence of a palladium catalyst, to afford the compound of Formula (G):

wherein:

R 1 is C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, —NR 5 -heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;

wherein any cycloalkyl or heterocyclyl is optionally substituted with one or more independently selected R 4 substituents;

wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR'S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, and heteroaryl;

wherein each cycloalkyl and heterocyclyl of the aryl or heteroaryl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl of the aryl or heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl;

each R 4 is independently halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , ═O, P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl;

wherein each cycloalkyl and heterocyclyl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl;

each R 7 is independently halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), ═O, cycloalkyl, or heterocyclyl;

each R 3 is independently H, halogen, or C 1-3 alkyl;

R 6 is H, halogen, C 1-3 alkyl, haloalkyl, hydroxyalkyl, or heteroalkyl;

X is —CR 5 R 5 —, —CR 5 OH—, or —O—; and

each R 5 is independently H or C 1-3 alkyl.

2. The process of claim 1 , wherein R 1 is aryl;

wherein the aryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, and heteroaryl;

wherein each cycloalkyl and heterocyclyl of the aryl or heteroaryl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl of the aryl or heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl.

3. The process of claim 2 , wherein R 1 is phenyl;

wherein the phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, and heteroaryl;

wherein each cycloalkyl and heterocyclyl of the aryl or heteroaryl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl of the aryl or heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl.

4. The process of claim 1 , wherein R 1 is heteroaryl;

wherein the heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, and heteroaryl;

wherein each cycloalkyl and heterocyclyl of the aryl or heteroaryl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl of the aryl or heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl.

5. The process of claim 1 , wherein each R 3 is independently H.

6. The process of claim 1 , wherein each R 3 is independently halogen.

7. The process of claim 6 , wherein each R 3 is independently F.

8. The process of claim 1 , wherein R 6 is H.

9. The process of claim 1 , wherein X is —CR 5 R 5 — or —CR 5 OH—.

10. The process of claim 9 , wherein X is —CR 5 R 5 —.

11. The process of claim 10 , wherein each R 5 is independently H.

12. The process of claim 9 , wherein X is —CR 5 OH—.

13. The process of claim 12 , wherein R 5 is H.

14. The process of claim 1 , wherein:

each R 3 is independently halogen;

R 6 is H;

X is —CR 5 R 5 — or —CR 5 OH—; and

each R 5 is independently H.

15. The process of claim 14 , wherein R 1 is aryl;

wherein the aryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, and heteroaryl;

wherein each cycloalkyl and heterocyclyl of the aryl or heteroaryl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl of the aryl or heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl.

16. The process of claim 15 , wherein R 1 is phenyl;

wherein the phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, and heteroaryl;

wherein each cycloalkyl and heterocyclyl of the aryl or heteroaryl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl of the aryl or heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl.

17. The process of claim 14 , wherein R 1 is heteroaryl;

wherein the heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , CH(CF 3 )NR 5 R 5 , hydroxyalkyl, heteroalkyl, C 1-4 alkylene-cycloalkyl, C 1-4 alkylene-heterocyclyl, aralkyl, C 1-4 alkylene-heteroaryl, C(O)C 1-6 alkyl, C(O)NR 5 R 5 , C(O)OR 5 , C(O)heterocyclyl, NR 5 R 5 , NHC(O)C 1-6 alkyl, NHC(O)NR 5 R 5 , NHC(O)heterocyclyl, NR 5 S(O) 2 C 1-6 alkyl, NR 5 S(O) 2 haloalkyl, NR 5 S(O) 2 NR 5 R 5 , NR 5 S(O) 2 heterocyclyl, O(alkyl), OC 1-4 alkylene-NR 5 R 5 , ONR 5 R 5 , P(O)(OC 1-3 alkyl) 2 , SC 1-6 alkyl, S(haloalkyl), SNR 5 R 5 , S(heterocyclyl), S(O)C 1-6 alkyl, S(O)haloalkyl, S(O)NR 5 R 5 , S(O)heterocyclyl, S(O) 2 C 1-6 alkyl, S(O) 2 haloalkyl, S(O) 2 NR 5 R 5 , S(O) 2 heterocyclyl, cycloalkyl, heterocyclyl, and heteroaryl;

wherein each cycloalkyl and heterocyclyl of the aryl or heteroaryl is optionally and independently substituted with one or more independently selected R 7 substituents; and

wherein each aryl of aralkyl and heteroaryl of the aryl or heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, C 1-6 alkyl, haloalkyl, C 1-4 alkylene-NR 5 R 5 , hydroxyalkyl, heteroalkyl, C(O)heterocyclyl, NR 5 R 5 , NHC(O)heterocyclyl, OH, O(alkyl), cycloalkyl, and heterocyclyl.

18. The process of claim 14 , wherein:

each R 3 is independently F;

X is —CR 5 R 5 —; and

each R 5 is independently H.

19. The process of claim 14 , wherein:

each R 3 is independently F;

X is —CR 5 OH—; and

R 5 is H.

20. The process of claim 1 , wherein the compound of Formula (G) is selected from the group consisting of:

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 26, 2022
From: MARX, MATTHEW ARNOLD; LEE, MATTHEW RANDOLPH; BOBINSKI, THOMAS P.; BURNS, AARON CRAIG; ARORA, NIDHI; CHRISTENSEN, JAMES GAIL; KETCHAM, JOHN MICHAEL
To: MIRATI THERAPEUTICS, INC.
Reel/Frame 060916/0574 →
Continuity (5)
Continuation 16966708
Provisional Application 62747736 · Oct 19, 2018
Provisional Application 62672701 · May 17, 2018
Provisional Application 62624176 · Jan 31, 2018
Related Publication 20230137025A1 · May 4, 2023
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