IP Library › Granted Patent US 12,594,274
Granted Patent B2
US 12,594,274 · App. 18/000,943 · Granted Apr 7, 2026

Method for preparing a crystalline form of rabeximod

Inventor: Ulf Björklund (Uppsala, SE)
Assignee: Gulch Pharma AB
A61K31/4985A61K9/0053A61K9/4808A61P19/02C07D487/04C07B2200/13
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Quick Facts
Patent No.
US 12,594,274
App. No.
18/000,943
Granted
Apr 7, 2026
Kind
B2
Abstract

The present invention relates to a process for preparing 9-Chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indolo-[2,3-b]quinoxaline, wherein said process is suitable for large scale synthesis.

Claims (22)

1 . A process for preparing 9-chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indolo-[2,3-b]quinoxaline (rabeximod) or a salt thereof, wherein the process comprises the step of:

reacting a solution or suspension of 9-chloro-2,3-dimethyl-6H-indolo[2,3-b]quinoxaline in the presence of an aqueous base sufficiently strong to deprotonize the indole N—H, with 2-chloro-N-(2-dimethylaminoethyl) acetamide or a salt thereof to obtain rabeximod or a salt thereof.

2 . The process of claim 1 , wherein a catalyst is present in the solution or suspension.

3 . The process of claim 1 , wherein 9-chloro-2,3-dimethyl-6H-indolo[2,3-b]quinoxaline or a salt thereof is dissolved in an organic solvent and wherein 2-chloro-N-(2-dimethylaminoethyl) acetamide or a salt thereof is dissolved in an organic solvent.

4 . The process of claim 1 , wherein the aqueous base is NaOH.

5 . The process of claim 1 , wherein 1 molar equivalent 9-chloro-2,3-dimethyl-6H-indolo[2,3-b]quinoxaline is deprotonized with at least 2 volumes of the aqueous base and wherein 9-chloro-2,3-dimethyl-6H-indolo[2,3-b]quinoxaline and the aqueous base are mixed at a suitable temperature until a clear solution is formed.

6 . The process of claim 2 , wherein the catalyst in a suitable amount is added under vigorous stirring and mixed for 10 to 60 minutes at a suitable temperature.

7 . The process of claim 1 , wherein 2-chloro-N-(2-dimethylaminoethyl) acetamide or a salt thereof is added to the solution of 9-chloro-2,3-dimethyl-6H-indolo[2,3-b]quinoxaline in the aqueous base and mixed for at least 1 hour at a suitable temperature.

8 . The process of claim 1 , wherein rabeximod is purified and isolated as a crystalline free base.

9 . The process of claim 1 , wherein the process comprises the preceding step of:

reacting a solution or suspension of 4,5-dimethyl-1,2-phenylenediamine with 5-chloroisatin under acidic conditions at elevated temperatures up to reflux to obtain the 9-chloro-2,3-dimethyl-6H-indolo[2,3-b]quinoxaline or a salt thereof.

10 . The process of claim 1 , wherein the process comprises the preceding step of:

reacting a solution or suspension of chloroacetyl chloride with N,N-dimethylethylene diamine to obtain the 2-chloro-N-(2-dimethylaminoethyl) acetamide or a salt thereof.

11 . The process of claim 1 , wherein the process comprises the preceding steps of

reacting a solution or suspension of 4,5-dimethyl-1,2-phenylenediamine with 5-chloroisatin under acidic conditions at elevated temperatures up to reflux to obtain 9-chloro-2,3-dimethyl-6H-indolo[2,3-b]quinoxaline or a salt thereof; and

reacting a solution or suspension of chloroacetyl chloride with N,N-dimethylethylene diamine to obtain 2-chloro-N-(2-dimethylaminoethyl) acetamide or a salt thereof.

12 . The process of claim 9 , wherein the acidic condition is an organic acid.

13 . The process of claim 9 , wherein 4,5-dimethyl-1,2-phenylenediamine and 5-chloroisatin are both dissolved in the acid before the reaction.

14 . The process of claim 9 , wherein the elevated temperature is reflux temperature.

15 . The process of claim 11 , wherein the acidic condition is an organic acid.

16 . The process of claim 11 , wherein 4,5-dimethyl-1,2-phenylenediamine and 5-chloroisatin are both dissolved in the acid before the reaction.

17 . The process of claim 11 , wherein the elevated temperature is reflux temperature.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 13, 2026
From: CYXONE AB
To: GULCH PHARMA AB
Reel/Frame 074859/0049 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2023
From: BJÖRKLUND, ULF
To: CYXONE AB
Reel/Frame 062372/0322 →
Priority Claims (4)
EP 20179239 · Jun 10, 2020 · regional
EP 20179277 · Jun 10, 2020 · regional
EP 20179279 · Jun 10, 2020 · regional
EP 20180706 · Jun 18, 2020 · regional
Continuity (1)
Related Publication 20230227455A1 · Jul 20, 2023
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