Pregabalin lactam methylene dimer and preparation method therefor

Patent metadata

Field	Value
Publication number	US-12018018-B2
Application number	US-201817291237-A
Country	US
Kind code	B2
Filing date	Nov 6, 2018
Priority date	Nov 6, 2018
Publication date	Jun 25, 2024
Grant date	Jun 25, 2024

Abstract

Provided are a pregabalin lactam methylene dimer and a preparation method therefor. The method comprises the following steps: dissolving pregabalin in a reaction solvent, reacting same with an aldehyde in an acidic system and isolating the obtained target product pregabalin lactam methylene dimer. The preparation method for pregabalin lactam methylene dimer provided by the present application has a simple operation, a high product yield, a good purity and a low cost.

First claim

The invention claimed is:

1. A pregabalin lactam methylene dimer having the following structural formula:

2. A method for preparing a pregabalin lactam methylene dimer, comprising following steps:
(a) adding pregabalin, an acid and an aldehyde to a reaction solvent to obtain a reaction system;
(b) heating the reaction system to a temperature of 30-100° C. to react for 0.5-36 hours; and
(c) obtaining the pregabalin lactam methylene dimer after the reaction is completed; wherein, the pregabalin lactam methylene dimer has the following structural formula:

3. The method according to claim 2 , wherein the reaction solvent in step (a) is selected from the group consisting of water, a polar organic solvent, and a mixture of water and the polar organic solvent.

4. The method according to claim 2 , wherein the acid in step (a) is selected from the group consisting of an organic acid, an inorganic acid, and a combination thereof.

5. The method according to claim 2 , wherein the aldehyde is selected from the group consisting of formaldehyde, formaldehyde dimer, metaformaldehyde and paraformaldehyde, or any combination thereof.

6. The method according to claim 2 , wherein a molar ratio of the acid to pregabalin in step (a) is 0.01:1-50:1.

7. The method according to claim 2 , wherein a molar ratio of the aldehyde to pregabalin in step (a) is 0.1:1-10:1.

8. The method according to claim 2 , wherein the temperature of the reaction system in step (b) is 55-75° C., and the reaction is performed for 12-24 hours.

9. The method according to claim 1 , wherein step (c) comprises: removing the reaction solvent to obtain a solid after the reaction is completed, and separating the solid to obtain the pregabalin lactam methylene dimer.

10. The method according to claim 9 , wherein separating is performed by column chromatography or preparative liquid chromatography.

11. The method according to claim 3 , wherein the polar organic solvent is selected from the group consisting of methanol, ethanol, propanol, isopropanol, acetonitrile, acetone, N,N-dimethylformamide, dimethylsulfoxide and N-methylpyrrolidone, or any combination thereof.

12. The method according to claim 4 , wherein the organic acid is selected from the group consisting of formic acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid, or any combination thereof and the inorganic acid is selected from the group consisting of hydrochloric acid, sulfuric acid, and phosphoric acid, or any combination thereof.

13. The method according to claim 5 , wherein the aldehyde is formaldehyde or metaformaldehyde.

14. The method according to claim 6 , wherein the molar ratio of the acid to pregabalin in step (a) is 0.1:1-2.5:1.

15. The method according to claim 7 , wherein the molar ratio of the aldehyde to pregabalin in step (a) is 0.3:1-3:1.

Assignees

• Zhejiang Huahai Pharm Co Ltd
• Zhejiang Huahai Zhicheng Pharmaceutical Co Ltd

Inventors

• Lin Jinsheng
• Liu Xiaofei
• Li Dan
• Wang Jing
• Li Yue
• Zhu Wenquan
• Chen Wenbin
• Li Min

Classifications

• C07B2200/07

  Optical isomers · CPC title

• C07D207/267 Primary

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom · CPC title

• C07D403/06 Primary

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D207/27 Primary

  with substituted hydrocarbon radicals directly attached to the ring nitrogen atom · CPC title