IP Library › Granted Patent US 12,391,691
Granted Patent B2
US 12,391,691 · App. 18/987,568 · Granted Aug 19, 2025

Synthesis of key intermediate of KRAS G12C inhibitor compound

Inventors: Andrew Thomas Parsons (Cambridge, MA); Brian McNeil Cochran (San Diego, CA); William Powazinik, IV (Thousand Oaks, CA); Marc Anthony Caporini (Belmont, MA)
Assignee: AMGEN INC.
C07D471/04C07C69/76C07C309/24
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Quick Facts
Patent No.
US 12,391,691
App. No.
18/987,568
Granted
Aug 19, 2025
Kind
B2
Abstract

The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure useful for the synthesis of compounds that target KRAS G12C mutations, such as

Claims (24)

1. A process for preparing a composition of Formula (4a):

comprising reacting a compound of Formula (4)

with a compound of Formula (B1)

in the presence of 2-methyltetrahydrofuran to form the composition of Formula (4a).

2. The process of claim 1 , wherein the process comprises preparing a suspension of the compound of Formula (4) in 2-methyltetrahydrofuran.

3. The process of claim 2 , wherein the compound of Formula (B1) is added to the suspension of the compound of Formula (4) in 2-methyltetrahydrofuran to provide a mixture of the compound of Formula (4) and the compound of Formula (B1) in 2-methyltetrahydrofuran.

4. The process of claim 3 , wherein a solution of Compound (4) and Compound (B1) in 2-methyltetrahydrofuran is prepared by heating the mixture of Compound (4) and Compound (B1) to dissolve any solids in the 2-methyltetrahydrofuran.

5. The process of claim 4 , wherein heptane is added to the solution to provide a suspension of the composition of Formula (4a).

6. The process of claim 5 , wherein, prior to adding heptane to the solution, the solution is filtered.

7. The process of claim 5 , wherein the suspension of the composition of Formula (4a) is filtered to provide the composition of Formula (4a) in a crystalline state.

8. The process of claim 7 , wherein the composition of Formula (4a) is treated with a base to produce a compound of Formula (5M):

9. The process of claim 8 , wherein the compound of Formula (5M) is used as an intermediate to generate a compound of Formula (9):

10. A process for preparing a compound of Formula (5M):

the process comprising:

a) reacting Compound (4):

with Compound (B1):

in the presence of 2-methyltetrahydrofuran to form a composition of Formula (4a):

as crystals;

b) isolating the composition of Formula (4a); and

c) treating the isolated composition Formula (4a) with a base to produce the compound of Formula (5M).

11. The process of claim 10 , wherein the base is Na 2 HPO 4 .

12. The process of claim 10 , wherein the base is NaHCO 3 .

13. The process of claim 10 , wherein the compound of Formula (5M) is used as an intermediate to generate a compound having the Formula (9):

14. The process of claim 13 , wherein the method further comprises mixing the compound of Formula (9) with at least one pharmaceutically acceptable excipient to form a pharmaceutical composition.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 17, 2025
From: PARSONS, ANDREW THOMAS; COCHRAN, BRIAN MCNEIL; POWAZINIK, WILLIAM, IV; CAPORINI, MARC ANTHONY
To: AMGEN INC.
Reel/Frame 071747/0805 →
Continuity (4)
Division 17689741 · Mar 8, 2022
Continuation 16685841 · Nov 15, 2019
Provisional Application 62768802 · Nov 16, 2018
Related Publication 20250206735A1 · Jun 26, 2025
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