Pleuromutilin hippuric acid ester with antibacterial activity and a method of preparing the same

Patent metadata

Field	Value
Publication number	US-11117859-B1
Application number	US-202117175575-A
Country	US
Kind code	B1
Filing date	Feb 12, 2021
Priority date	Feb 12, 2021
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

A compound with anti-drug resistant bacteria activity having the following formula

(I) is disclosed. The methods of preparing the compound of formula (I) are also disclosed.

First claim

What is claimed is:

1. A compound having the following formula (I):

2. A method of preparing the compound of formula (I) of claim 1 , comprising: reacting a compound of formula (II) with a compound of formula (III) to obtain the compound of formula (I):

3. The method of claim 2 , wherein the reaction of the compound of formula (II) with the compound of formula (III) comprises the following steps:
placing the compound of formula (II) and the compound of formula (III), in a molar ratio of 1:1 to 1:1.3, in a reactor;
adding an organic solvent and a catalytic amount of 4-dimethylaminopyridine (4-DMAP) under nitrogen atmosphere to obtain a reaction mixture;
stirring the reaction mixture at 0° C. for five minutes and then adding N,N′-dicyclohexylcarbodiimide (DCC) to the reaction mixture;
reacting the reaction mixture at 25-70° C. for 3 to 7 hours;
concentrating the reaction mixture and extracting with ethyl acetate to obtain a crude product; and
purifying the crude product on a silica gel fresh chromatography column with petroleum ether and ethyl acetate with a ratio of 1:1 to 4:1 as an eluent to obtain the compound of formula (I).

4. The method of claim 3 , the organic solvent is toluene, 1,2-dichloroethane, or dimethylformamide (DMF).

5. The method of claim 4 , wherein the organic solvent is 1,2-dichloroethane.

6. The method of claim 3 , wherein the molar ratio of the compound of formula (II) and the compound of formula (III) is 1:1.1.

7. The method of claim 3 , wherein the reaction mixture is heated at 60° C.

8. The method of claim 3 , wherein the reaction mixture is reacted for 5 hours.

9. The method of claim 3 , wherein the eluent is petroleum ether:ethyl acetate=3:1.

10. The method of claim 2 , wherein the reaction of the compound of formula (II) with the compound of formula (III) comprises the following steps:
placing the compound of formula (II), a catalyst, and an ionic liquid in a reactor under nitrogen atmosphere, the catalyst being 12-molybdosilicic acid hydrate (H 6 Mo 12 O 41 Si);
adding the compound of formula (III) to the reactor to form a reaction mixture;
heating the reaction mixture at 20-60° C. for 4-8 hours;
placing the reaction mixture in a separating funnel to separate a crude product;
purifying the crude product by recrystallization in methanol to obtain the compound of formula (I); and
recycling the ionic liquid.

11. The method of claim 10 , wherein the ionic liquid is 1-octyl-3-methylimidazolium hexafluorophosphate (C 12 H 23 F 6 N 2 P),1-hexyl-3-methylimidazolium tetrafluoroborate or 1-butyl-3-methylimidazolium tetrafluoroborate.

12. The method of claim 11 , wherein the ionic liquid is the ionic liquid is 1-octyl-3-methylimidazolium hexafluorophosphate.

13. The method of claim 10 , wherein the compound of formula (II) and the compound (III) have a molar ratio of 1:1 to 1:1.3.

14. The method of claim 13 , wherein the molar ratio of the compound of formula (II) and the compound of formula (III) is 1:1.1.

15. The method of claim 10 , wherein the reaction mixture is heated at 30° C.

16. The method of claim 10 , wherein the reaction mixture is heated for 6 hours.

Assignees

• Yang Dan
• Li Jingyi
• Xin Liang
• Zhao Qianqian
• Qi Liang
• Tian Bin
• Zha Jian
• Yao Wenbo
• Mao Gennian
• Li Han
• Shi Chunyang
• Wang Yongbo
• Xu Jingwen
• Univ Shaanxi Science & Tech

Inventors

• Yang Dan
• Li Jingyi
• Xin Liang
• Zhao Qianqian
• Qi Liang
• Tian Bin
• Zha Jian
• Yao Wenbo
• Mao Gennian
• Li Han
• Shi Chunyang
• Wang Yongbo
• Xu Jingwen

Classifications

• C07C2603/82

  having three condensed rings with in total fourteen carbon atoms and having a having a [5.4.3.0(1,8)] ring structure, e.g. pleuromutiline · CPC title

• C07C233/83 Primary

  of an acyclic saturated carbon skeleton · CPC title

• C07B2200/07

  Optical isomers · CPC title

• C07C231/24

  Separation; Purification · CPC title

• C07C231/12

  by reactions not involving the formation of carboxamide groups · CPC title