Preparation method of tedizolid phosphate

A technology of tedizolid phosphate and compound, applied in the field of preparation of tedizolid phosphate, can solve the problems of high price, impurity and high cost, and achieve the effects of reducing catalyst cost, mild reaction conditions and increasing solubility

Inactive Publication Date: 2018-02-23
CHONGQING HUABANGSHENGKAI PHARM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] (2) The route in CN102177156 uses 3-fluoro-4-bromoaniline as the starting material and has a long synthesis reaction route, in which the second step of the boronation reaction needs to be carried out at a low temperature of -72°C and the obtained product 4-(benzyloxycarbonylamino) The yield of -2-fluorophenylboronic acid is only 66% and it is very impure. The fourth step of the cyclization reaction needs to use expensive reagents as a catalyst, and the cost is high. The purity of the precursor is low, resulting in low purity of tedizolid phosphate obtained by phosphorylation in the last step
[0010] There are many defects in the synthetic method of tedizolid phosphate disclosed in the prior art, so there is still a need to prepare a new method for tedizolid phosphate

Method used

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  • Preparation method of tedizolid phosphate
  • Preparation method of tedizolid phosphate
  • Preparation method of tedizolid phosphate

Examples

Experimental program
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Effect test

Embodiment 1

[0057] The preparation method of the compound shown in embodiment 1 formula Z1

[0058] Add 50g of the compound of formula X3, 400ml of tetrahydrofuran, and 400ml of acetonitrile into a 1L three-necked flask, blow nitrogen into it, control the temperature at 25°C, the solid is insoluble, then add 19.8g of lithium tert-butoxide, the solid is dissolved, and the reaction solution changes from colorless to Yellow color, after stirring for 2 hours, add 19.7 g of R-(-)-glycidyl butyric acid and the compound of formula R dropwise to the reaction solution, keep warm for 3 hours after the dropwise addition, and take a sample for TLC (developer: chloroform / Methanol = 10 / 1), when the spots of the compound of formula X3 disappear, add dropwise dilute hydrochloric acid prepared from concentrated hydrochloric acid and water, adjust the pH to 8, and stir thoroughly for 30 minutes. Concentrate under reduced pressure at 0.07MPa~-0.1MPa to cut off the flow to obtain the compound represented by...

Embodiment 2

[0059] The preparation method of the compound shown in embodiment 2 formula Z1

[0060] Add 50g of the compound of formula X3, 400ml of tetrahydrofuran, and 400ml of acetonitrile into a 1L three-necked flask, blow nitrogen into it, control the temperature at 25°C, the solid is insoluble, then add 23.8g of sodium tert-butoxide, the solid is dissolved, and the reaction solution changes from colorless to Yellow color, after stirring for 2 hours, add 19.7 g of R-(-)-glycidyl butyric acid and the compound of formula R dropwise to the reaction solution, keep warm for 3 hours after the dropwise addition, and take a sample for TLC (developer: chloroform / Methanol = 10 / 1), when the spots of the compound of formula X3 disappear, add dropwise dilute hydrochloric acid prepared from concentrated hydrochloric acid and water, adjust the pH to 8, and stir thoroughly for 30 minutes. Concentrate under reduced pressure at 0.07MPa~-0.1MPa to cut off the flow to obtain the compound represented by ...

Embodiment 3

[0061] The preparation method of the compound shown in embodiment 3 formula Z1

[0062] Add 50g of the compound of formula X3, 400ml of tetrahydrofuran, and 400ml of acetonitrile into a 1L three-necked flask, blow nitrogen into it, control the temperature at 25°C, the solid is insoluble, then add 27.8g of potassium tert-butoxide, the solid dissolves, and the reaction solution changes from colorless to Yellow color, after stirring for 2 hours, add 19.7 g of R-(-)-glycidyl butyric acid and the compound of formula R dropwise to the reaction solution, keep warm for 3 hours after the dropwise addition, and take a sample for TLC (developer: chloroform / Methanol = 10 / 1), when the spots of the compound of formula X3 disappear, add dropwise dilute hydrochloric acid prepared from concentrated hydrochloric acid and water, adjust the pH to 8, and stir thoroughly for 30 minutes. Concentrate under reduced pressure at 0.07MPa~-0.1MPa to cut off the flow to obtain the compound represented by ...

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Abstract

The invention belongs to the field of pharmaceutical and chemical industry, and specifically relates to a preparation method of tedizolid phosphate. The compound shown as a formula Z1 is a tedizolid phosphate precursor, and is obtained in a cyclization reaction through catalyst catalysis by using X3 as a raw material. The preparation method of the compound shown as the formula Z1 comprises the following steps: carrying out the cyclization reaction on a compound shown as a formula X2 and a compound shown as a formula R under the existence of a catalyst and a solvent, so as to obtain the compound shown as a formula Z1; carrying out a phosphorylation reaction on the compound shown as the formula Z1 so as to obtain tedizolid phosphate. According to the preparation method disclosed by the invention, the compound with high boiling point such as DMPU is prevented from being used as the catalyst, and the dissolubility of the reaction system is improved through the addition of a mixed solvent,so that the reaction time is greatly shortened, and the compound is applicable for industrial production.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and in particular relates to a preparation method of tedizolid phosphate. Background technique [0002] Tedizolid phosphate, (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)3-fluorophenyl)-5-hydroxymethyl Oxazolidin-2-one dihydrogen phosphate (formula I), the following structural formula, the drug is used for the treatment of Gram-positive bacterial infections, such as acute bacterial skin infections, infections caused by MRSA and lung infections. [0003] [0004] Tedizolid phosphate is an oxazolidinone antibiotic, suitable for the treatment of Gram-positive bacteria such as Staphylococcus aureus (including methicillin-resistant strains and methicillin-sensitive strains), various streptococci and enterococci. Acute bacterial skin tissue infection in adults. Tedizolid phosphate is a prodrug that is rapidly converted in vivo to biologically active tedizolid by phosphatases. [0...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/6558
CPCC07F9/65583
Inventor 刘双邹长忠罗炼
Owner CHONGQING HUABANGSHENGKAI PHARM
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