Preparation method for tedizolid, tedizolid intermediate, and preparation method therefor

Patent metadata

Field	Value
Publication number	US-10385079-B2
Application number	US-201615772521-A
Country	US
Kind code	B2
Filing date	Nov 2, 2016
Priority date	Nov 3, 2015
Publication date	Aug 20, 2019
Grant date	Aug 20, 2019

Abstract

The present invention relates to a preparation method for a tedizolid compound in Formula I. In Formula I, R is selected from hydrogen, formula A, formula B, benzyl or benzyl substituted by a substituent, the substituent is selected from a group consisting of halogen, nitryl, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy, and R 1 is C 1 -C 6 alkyl or C 1 -C 6 alkyl substituted by halogen. The method comprises: generating a compound having a structure as shown in Formula C and a compound having a structure as shown in Formula D by a coupled reaction under the catalysis of a metal catalyst, a substituent of R being defined as above, where X is a leaving group, the leaving group comprising chlorine, bromine, iodine, and sulfonyl oxy such as trifluoromethane sulfonic oxy, methylsulfonyl oxy and benzenesulfonyl oxy, or benzenesulfonyl oxy substituted by one or more substituents, the substituent being selected from a group consisting of halogen, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy.

First claim

What is claimed is:

1. A preparation method for tedizolid compound of the formula below

wherein R is selected from the group consisting of hydrogen,

benzyl and benzyl substituted by a substituent selected from the group consisting of halogen, nitro, C 1 -C 6 alkyl and C 1 -C 6 alkoxy, and R 1 is C 1 -C 6 alkyl or C 1 -C 6 alkyl substituted by halogen;
wherein the preparation method comprises reacting the compound having a structure of the formula below

wherein X is a leaving group selected from the group consisting of chlorine, bromine, iodine, and sulfonyloxy;
with the compound having a structure of the formula below

under the catalysis of metal catalyst in the presence of an alkaline substance as a promoter, in a reaction solvent selected from the group consisting of toluene, chlorobenzene, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, dioxane, isopropanol, ethanol and acetonitrile, at a reaction temperature of 60-110° C. to produce the tedizolid compound by a coupled reaction, and wherein substituent R is as defined above.

2. The preparation method according to claim 1 , wherein the metal catalyst is a copper catalyst or a palladium catalyst.

3. The preparation method according to claim 1 , wherein when the metal catalyst is a copper catalyst, the copper catalyst acts together with ligands selected from the group consisting of a diamine ligand, a diketone ligand, a phenanthroline ligand, an amino acid ligand, and a Phos ligand.

4. The preparation method according to claim 1 , wherein the sulfonyloxy is selected from the group consisting of trifluoromethane sulfonyloxy, methanesulfonyloxy, benzenesulfonyloxy, and benzenesulfonyloxy substituted by one or more substituent(s) selected from the group consisting of halogen, C 1 -C 6 alkyl and C 1 -C 6 alkoxy.

5. The preparation method according to claim 2 , wherein the copper catalyst is selected from the group consisting of CuI, CuBr, CuCl, CuO, Cu 2 O, CuSO 4 , Cu(OAc) 2 , Cu(OTf) 2 and Cu powder; and/or the palladium catalyst is selected from the group consisting of palladium chloride, palladium acetate, bis(dibenzylideneacetone) palladium, tetrakis(triphenylphosphine) palladium, tris(dibenzylideneacetone) dipalladium, dichloro [1, 1′-bis(diphenylpho sphino)ferrocene] palladium, dichlorobis(tricyclohexylphosphine) palladium and dichlorobis(triphenylphosphine) palladium.

6. The preparation method according to claim 1 , wherein the alkaline substance is selected from the group consisting of potassium carbonate, sodium carbonate, cesium carbonate, cesium fluoride, potassium acetate, sodium hydroxide, potassium hydroxide, potassium phosphate and sodium phosphate.

7. The preparation method according to claim 1 , wherein the reaction temperature is 90-110° C.

8. The preparation method according to claim 3 , wherein the diamine ligand is selected from the group consisting of:

the diketone ligand is selected from the group consisting of:

the phenanthroline ligand is selected from the group consisting of:

the amino acid ligand is

and the Phos ligand is selected from the group consisting of X-Phos, XantPhos, RuPhos, BrettPhos, SPhos, DavePhos, JohnPhos and tBuXPhos.

Assignees

• Zhejiang Huahai Pharm Co Ltd
• Shanghai Syncores Tech Inc Ltd

Inventors

• Li Siyuan
• Gui Shaoxiao
• Zhang Jicheng
• Huang Luning
• Tao Anping
• Gu Hong

Classifications

• C07D263/20

  attached in position 2 · CPC title

• C07C235/78

  the carbon skeleton containing rings · CPC title

• C07C231/10

  from compounds not provided for in groups C07C231/02 - C07C231/08 · CPC title

• C07C217/48

  the carbon skeleton being unsaturated and containing rings · CPC title

• C07C213/00

  Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton · CPC title