Pleuromutilin (phenylthio)acetic acid ester with anti-drug resistant bacteria activity and a method of preparing the same

Patent metadata

Field	Value
Publication number	US-11518740-B2
Application number	US-202117239575-A
Country	US
Kind code	B2
Filing date	Apr 24, 2021
Priority date	Apr 24, 2021
Publication date	Dec 6, 2022
Grant date	Dec 6, 2022

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 with antibacterial activity against drug resistant bacteria 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 triethylamine under a nitrogen atmosphere to obtain a reaction mixture;
heating the reaction mixture at 20-60° C. for 3-6 hours;
extracting the reaction mixture with ethyl acetate to obtain a crude product; and
purifying the crude product on a silica gel chromatography column with petroleum ether and ethyl acetate as an eluent to obtain the compound of formula (I).

4. The method of claim 3 , wherein the organic solvent is toluene, dichloromethane or N,N-dimethylformamide.

5. The method of claim 4 , wherein the organic solvent is dichloromethane.

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 25° C.

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

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

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

11. The method of claim 10 , wherein the reaction of the compound of formula (II) with the compound of formula (IV) 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 of formula H 6 Mo 12 O 41 Si;
adding the compound of formula (IV) to the reactor to form a reaction mixture;
heating the reaction mixture at 20-50° 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.

12. The method of claim 11 , wherein the ionic liquid is 1-octyl-3-methylimidazolium hexafluorophosphate, 1-hexyl-3-methylimidazolium tetrafluoroborate, or 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF 4 ]).

13. The method of claim 12 , wherein the ionic liquid is 1-butyl-3-methylimidazolium tetrafluoroborate.

14. The method of claim 11 , wherein the compound of formula (II) and the compound (IV) have a molar ratio of 1:1 to 1:1.3.

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

16. The method of claim 11 , wherein the reaction mixture is heated at 30° C.

17. The method of claim 11 , wherein the reaction mixture is heated for 6 hours.

Assignees

• Zhao Qianqian
• Zhang Jie
• Xin Liang
• Li Jingyi
• Bian Ruina
• Zhao Yuqing
• Yang Dan
• Li Han
• Tian Bin
• Wang Yongbo
• Liang Chengyuan
• Univ Shaanxi Science & Tech

Inventors

• Zhao Qianqian
• Zhang Jie
• Xin Liang
• Li Jingyi
• Bian Ruina
• Zhao Yuqing
• Yang Dan
• Li Han
• Tian Bin
• Wang Yongbo
• Liang Chengyuan

Classifications

• C07C319/20 Primary

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

• C07C323/52 Primary

  the carbon skeleton being acyclic and saturated · CPC title

• 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