IP Library › Granted Patent US 12,312,325
Granted Patent B2
US 12,312,325 · App. 18/114,050 · Granted May 27, 2025

Methods and compounds useful in the synthesis of an AAK1 inhibitor

Inventors: Tao Chen (Wuxi, CN); Wenxue Wu (Princeton Junction, NJ); Jun Yan (Changzhou, CN); Xianglu Zeng (Changzhou, CN); Matthew Mangzhu Zhao (Edison, NJ)
Assignee: LEXICON PHARMACEUTICALS, INC.
C07D401/04B01J31/2295B01J2531/824
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Quick Facts
Patent No.
US 12,312,325
App. No.
18/114,050
Granted
May 27, 2025
Kind
B2
Abstract

Methods for the synthesis of (S)-1-((2′,6-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine and salts thereof are disclosed, as well as compounds useful therein.

Claims (26)

1. A method of preparing(S)-1-((2′,6-bis(difluoromethyl)-[2,4′-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine (Compound J):

which comprises contacting Compound H:

with Compound D:

or a salt thereof in the presence of a base under conditions sufficient to form Compound J.

2. The method of claim 1 , wherein the base is an alkoxide.

3. The method of claim 2 , wherein the alkoxide is potassium tert-butoxide.

4. The method of claim 3 , wherein Compound H is prepared by contacting Compound Q:

with a fluorinating agent under conditions sufficient to form Compound H.

5. The method of claim 4 , wherein the fluorinating agent is DAST.

6. The method of claim 5 , wherein Compound Q is prepared by contacting Compound P:

with an acid under conditions sufficient to form Compound Q.

7. The method of claim 6 , wherein the acid is hydrochloric acid.

8. The method of claim 7 , wherein Compound P is prepared by contacting Compound L:

with Compound N:

under conditions sufficient to form Compound P.

9. The method of claim 5 , wherein Compound Q is prepared by contacting Compound L4:

with an acid under conditions sufficient to form Compound Q.

10. The method of claim 9 , wherein the acid is hydrochloric acid.

11. The method of claim 10 , wherein Compound L4 is prepared by contacting Compound L3:

with Compound L1:

in the presence of a catalyst, ligand, and base under conditions sufficient to form Compound L4.

12. The method of claim 11 , wherein the catalyst is Pd2(dba)2.

13. The method of claim 12 , wherein the ligand is Xphos.

14. The method of claim 11 , wherein the base is sodium carbonate.

15. The method claim 1 , wherein the salt of Compound D is a benzoate salt.

16. The method of claim 13 , wherein the solvent is isopropyl alcohol.

Assignments (7)
RELEASE OF SECURITY INTEREST Recorded May 5, 2026
From: OXFORD FINANCE LLC
To: LEXICON PHARMACEUTICALS, INC.; LEXICON PHARMACEUTICALS
Reel/Frame 075545/0601 →
SECURITY INTEREST Recorded May 4, 2026
From: LEXICON PHARMACEUTICALS, INC.; LEXICON PHARMACEUTICALS (NEW JERSEY), INC.; LION ACQUISITION CORPORATION
To: HERCULES CAPITAL, INC., AS AGENT
Reel/Frame 075498/0899 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 2, 2023
From: WU, WENXUE; ZHAO, MATTHEW MANGZHU
To: LEXICON PHARMACEUTICALS, INC.
Reel/Frame 064135/0567 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 29, 2023
From: LEXICON PHARMACEUTICALS (NEW JERSEY), INC.
To: LEXICON PHARMACEUTICALS, INC.
Reel/Frame 064109/0165 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 28, 2023
From: WUXI APPTEC CO., LTD.
To: LEXICON PHARMACEUTICALS (NEW JERSEY), INC.
Reel/Frame 064095/0031 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 27, 2023
From: CHEN, TAO; YAN, JUN; ZENG, XIANGLU
To: WUXI APPTEC CO., LTD.
Reel/Frame 064084/0406 →
AMENDMENT TO PREVIOUSLY FILED SECURITY INTEREST Recorded May 17, 2023
From: LEXICON PHARMACEUTICALS, INC.
To: OXFORD FINANCE LLC
Reel/Frame 063666/0326 →
Continuity (2)
Provisional Application 63315504 · Mar 1, 2022
Related Publication 20230357181A1 · Nov 9, 2023
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