Method for preparing benzamide derivative, novel intermediate used in preparation of benzamide, and method for preparing novel intermediate

• US 9,771,348 B2
• Filed: 07/11/2014
• Issued: 09/26/2017
• Est. Priority Date: 07/25/2013
• Status: Active Grant

• Current Assignee: Dong-A ST Co., Ltd.
• Original Assignee: Dong-A ST Co., Ltd.
• Inventors: Kwak, Woo Young, Lee, Kyung Seok, Reddy, Ullapu Punna, Jung, Soon Kyu, Park, Tae Sun, Lim, Joong In
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US14/907,267
• Publication Number:
  US 20160185751A1
• Time in Patent Office: 1,173 Days
• Field of Search: 546210
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: C07C 55/14 Adipic acid
• CPC Class Codes: C07C 57/145 Maleic acid
• CPC Class Codes: C07C 57/15 Fumaric acid
• CPC Class Codes: C07C 59/255 Tartaric acid
• CPC Class Codes: C07C 59/265 Citric acid
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The present invention relates to a method for preparing N-[[1-{3-(1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methyl]-4-amino-5-chloro-2-methoxybenzamide, which is a novel benzamide derivative as a 5-HT4 receptor agonist, or a pharmaceutically acceptable salt thereof; to a novel intermediate capable of being used in the preparation of the compounds; and to a method for preparing the same. The preparation methods of the present invention can be useful for mass production since a low-priced reagent and intermediate are used and the number of reaction processes is decreased, thereby saving preparation costs and improving the yield.

Claims

1. A method for preparing a compound of Formula 3:

2. The method of claim 1, wherein the reaction of the compound of Formula 1 with the compound of Formula 2 or the pharmaceutically acceptable salt thereof is conducted in the presence of at least one compound selected from the group consisting of isobutyl chloroformate, ethyl chloroformate, carbonyldiimidazole, N-(3-dimethylaminopropyl)-N′

-ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole.

3. The method of claim 1, wherein the reaction of the compound of Formula 1 with the compound of Formula 2 or the pharmaceutically acceptable salt thereof is conducted in the presence of a base.

4. The method of claim 3, wherein the base is a tertiary amine.

5. The method of claim 4, wherein the tertiary amine is at least one selected from the group consisting of N-methylmorpholine, isopropylethylamine, triethylamine and pyridine.

6. The method of claim 1, wherein the preparation of salt of the compound of Formula 3 further comprises reacting the compound of Formula 3 with an acid.

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

8. The method of claim 6, wherein the reaction between the compound of Formula 3 and the acid is conducted in the presence of at least one solvent selected from the group consisting of an alcohol, a ketone and an ether.

9. The method of claim 6, wherein the reaction between the compound of Formula 3 and the acid is conducted in the presence of at least one solvent selected from the group consisting of a C₁-C₅ alcohol, a C₃-C₁₀ ketone and a C₂-C₁₀ ether.

10. The method of claim 1, wherein the compound of Formula 2 or the pharmaceutically acceptable salt thereof is prepared by a method comprising:

preparing a compound of Formula 6;

11. The method of claim 10, wherein the compound of Formula 5 is prepared by a method comprising:

preparing a compound of Formula 8;

12. The method of claim 11, wherein the cyclization of the compound of Formula 8 comprises reacting the compound of Formula 8 with a carbide compound in the presence of sodium ascorbate and copper iodide.

13. A compound of Formula 6:

14. The compound of claim 13, wherein the pharmaceutically acceptable salt is hydrochloride, sulfate, phosphate, oxalate, adipate, citrate, di-p-toluoyl-L-tartarate, di-p-toluoyl-D-tartarate, citrate, lactate, maleate, fumarate, gluconate, methanesulfonate, acetate, glycolate, succinate, L- or D-tartarate, tartarate, 4-toluenesulfonate, trifluoroacetate, galacturonate, embonate, glutamate or aspartate.

15. A compound selected from the group consisting of:

1-[{3-(1H-1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methanamine hydrochloride;

1-[{3-(1H-1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methanamine;

1-[{3-(1H-1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methanamine oxalate;

1-[{3-(1H-1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methanamine succinate;

1-[{3-(1H-1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methanamine adipate;

1-[{3-(1H-1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methanamine citrate;

1-[{3-(1H-1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methanamine L-tartarate;

1-[{3-(1H-1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methanamine D-tartarate;

1-[{3-(1H-1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methanamine fumarate; and

1-[{3-(1H-1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methanamine maleate.

16. A method for preparing a compound of Formula 6:

17. The method of claim 16, wherein the reaction between the compound of Formula 4 and the compound of Formula 5 is conducted in the presence of at least one compound selected from the group consisting of sodium iodide and potassium iodide.

18. The method of claim 16, wherein the reaction between the compound of Formula 4 and the compound of Formula 5 is conducted in the presence of a base.

19. The method of claim 18, wherein the base is at least one selected from the group consisting of sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, N-methyl morpholine, isopropylethylamine, triethylamine and pyridine.

20. A method for preparing a compound of Formula 2:

21. The method of claim 20, wherein removing the amine protecting groups comprises reacting the compound of Formula 6 with an acid.

22. The method of claim 20, wherein removing the amine protecting groups comprises performing a hydrogenation of the compound of Formula 6 in the presence of palladium/carbon.