Granted Patent B2

US 12,338,232 · App. 18/315,291 · Granted Jun 24, 2025

Inventors: Shanghai Yu (Kun Shan, CN); Ben Li (Kun Shan, CN)

Assignee: Terns, Inc.

C07D403/12

Abstract

Claims (62)

1. A method of synthesizing a compound of Formula (I):

or a pharmaceutically acceptable salt thereof;

wherein:

Ring A is a C 5-10 aliphatic ring or a C 5-10 aromatic ring, each optionally substituted with one or more substituents independently selected from the group consisting of hydrogen, halogen atoms, hydroxy, —OCF 3 , —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl) 2 , —CONH 2 , —CONHC 1-4 alkyl, —CON(C 1-4 alkyl) 2 , —NHCOC 1-4 alkyl, C 1-6 alkyl, C 1-6 alkoxy, and C 3-6 cycloalkyl, and when two substituents are contained, the two substituents can form a ring structure together with the carbon connected thereto; and the halogen atoms are selected from the group consisting of F, Cl and Br;

R 2 and R 3 are each independently selected from the group consisting of halogen atoms, and substituted or unsubstituted C 1-6 alkyl, the substituent being selected from the group consisting of halogen atoms, hydroxy, and C 1-6 alkoxy; and

R 1 is selected from the group consisting of hydrogen, cyano, substituted or unsubstituted C 1-6 alkyl, and substituted or unsubstituted C 3-6 cycloalkyl, the substituent being selected from the group consisting of halogen atoms, hydroxy, and C 1-6 alkoxy;

comprising a step of contacting a compound of Formula (I-c):

or a salt thereof, with a compound of Formula (I-d):

or a salt thereof, to produce a compound of Formula (I-e):

or a salt thereof.

2. The method of claim 1 , wherein the step of contacting the compound of Formula (I-c) with the compound of Formula (I-d) takes place in the presence of a base.

3. The method of claim 1 , further comprising a step of subjecting the compound of Formula (I-e):

or a salt thereof, to an alkaline or acidic environment at a high temperature to produce a compound of Formula (I-f):

or a salt thereof.

4. The method of claim 3 , wherein the high temperature is greater than 100° C.

5. The method of claim 3 , wherein the alkaline or acidic environment comprises acetic acid and sodium acetate.

6. The method of claim 3 , wherein the alkaline environment comprises sodium hydroxide.

7. The method of claim 1 , further comprising a step of contacting a compound of Formula (I-f):

or a salt thereof, with a compound of Formula I-g:

or a salt thereof, to produce the compound of Formula (I):

or a salt thereof.

8. The method of claim 7 , wherein the step of contacting the compound of Formula (I-f), or a salt thereof, with the compound of Formula (I-g), or a salt thereof, takes place in the presence of a nitrite, in an acidic aqueous solution.

9. The method of claim 8 , wherein the nitrite is sodium nitrite.

10. The method of claim 7 , wherein the acidic aqueous solution comprises hydrochloric acid.

11. The method of claim 7 , wherein the method further comprises contacting with acetic acid and sodium acetate.

12. The method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (II):

wherein,

R 2 and R 3 are each independently selected from the group consisting of halogen atoms and substituted or unsubstituted C 1-6 alkyl, the substituent being selected from the group consisting of halogen atoms, hydroxy, and C 1-6 alkoxy; and

R 1 is selected from the group consisting of hydrogen, cyano, substituted or unsubstituted C 1-6 alkyl, and substituted or unsubstituted C 3-6 cycloalkyl, the substituent being selected from the group consisting of halogen atoms, hydroxy, and C 1-6 alkoxy;

L is not present or is selected from the group consisting of —CH 2 — and —CH 2 CH 2 —;

R 4 is selected from the group consisting of hydrogen, halogen atoms, hydroxy, —OCF 3 , —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl) 2 , C 1-6 alkyl, C 1-6 alkoxy, and C 3-6 cycloalkyl;

n is an integer from the range 1 to 4;

m is an integer from the range 1 to 4;

when L is not present, the ring may have two or more substituents R 4 thereon; and

the halogen atoms are selected from the group consisting of F, Cl, and Br.

13. The method of claim 12 , wherein:

R 4 is selected from the group consisting of hydrogen and C 1-3 alkyl;

L is not present;

n is 1, 2 or 3; and

m is 1 or 2.

14. The method of claim 12 , wherein:

R 4 is selected from the group consisting of hydrogen and C 1-3 alkyl;

L is —CH 2 — or —CH 2 CH 2 —;

n is 1, 2 or 3; and

m is 1 or 2.

15. The method of claim 1 , wherein Ring A is a C 5-10 aromatic ring optionally substituted with one or more substituents independently selected from the group consisting of hydrogen, halogen atoms, hydroxy, —OCF 3 , —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl) 2 , —CONH 2 , —CONHC 1-4 alkyl, —CON(C 1-4 alkyl) 2 , —NHCOC 1-4 alkyl, C 1-6 alkyl, C 1-6 alkoxy, and C 3-6 cycloalkyl, and when two substituents are contained, the two substituents can form a ring structure together with the carbon connected thereto; and the halogen atoms are selected from the group consisting of F, Cl, and Br.

16. The method of claim 15 , wherein the compound of Formula (I) is a compound of Formula (III):

wherein:

R 2 and R 3 are each independently selected from the group consisting of halogen atoms and substituted or unsubstituted C 1-6 alkyl, the substituent being selected from the group consisting of halogen atoms, hydroxy, and C 1-6 alkoxy; and

R 1 is selected from the group consisting of hydrogen, cyano, substituted or unsubstituted C 1-6 alkyl, and substituted or unsubstituted C 3-6 cycloalkyl, the substituent being selected from the group consisting of halogen atoms, hydroxy, and C 1-6 alkoxy;

R 4 is selected from the group consisting of hydrogen, halogen atoms, hydroxy, —OCF 3 , —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl) 2 , —CONH 2 , —CONHC 1-4 alkyl, —CON(C 1-4 alkyl) 2 , —NHCOC 1-4 alkyl, C 1-6 alkyl, C 1-6 alkoxy, and C 3-6 cycloalkyl;

m is an integer from the range 1 to 4; and

the halogen atoms are selected from the group consisting of F, Cl, and Br.

17. The method of claim 16 , wherein R 4 is selected from the group consisting of hydrogen, halogen atoms, hydroxy, —OCF 3 , C 1-6 alkyl, C 1-6 alkoxy, and C 3-6 cycloalkyl; and m is an integer from the range 1 to 3.

18. The method of claim 17 , wherein R 4 is selected from the group consisting of hydrogen, halogen atoms, and C 1-3 alkyl; and m is 1 or 2.

19. The method of claim 18 , wherein R 4 is hydrogen.

20. The method of claim 1 , wherein the compound of Formula (I) is selected from the following compounds:

21. The method of claim 1 , wherein the compound of Formula (I) is selected from the following compounds:

22. The method of claim 1 , wherein the compound of Formula (I) is

23. The method of claim 1 , wherein the compound of Formula (I) is

24. The method of claim 1 , wherein the compound of Formula (I) is

25. The method of claim 1 , wherein the compound of Formula (I) is

Assignments (4)

Priority Claims (1)

Continuity (5)

References Cited (236)

Cited By (3)

US 12,459,926 US 12,485,118 US 12,528,791