Preparation method of high-purity tedizolid phosphate

Abstract

The invention provides a preparation method of high-purity tedizolid phosphate. The preparation method comprises the following steps: step 1, with 2-methyl-5-(5-bromopyridin-2-yl) tetrazole as a starting material, tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) as a catalyst, carrying out reacting with bis(pinacolato)diboron to generate a compound as shown in a formula 1, namely bromine-converted pinacol borate; 2, subjecting a compound as shown in the formula 3 and (5R)-3-(4-bromo-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one to Suzuki coupling under the catalytic action of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) to obtain (R)-3-[4-[2-(2-methyltetrazol-5-yl)pyrid-5-yl]-3-fluorophenyl]-5-hydroxymethyl oxazolidine; and 3, preparing tedizolid phosphate from a compound as shownin a formula 5 under the condition of phosphorylation of phosphorus oxychloride. The method for preparing tedizolid phosphate has the advantages that ultralow-temperature operation is not needed, andreaction is simple; the purity of tedizolid phosphate is high and can reach 95% or higher; byproducts are few, and yield is high and is higher than 70%; and process is stable, and operability is high.

Description

technical field [0001] The invention belongs to the field of preparation of tedizolid phosphate, in particular to a preparation method of high-purity tedizolid phosphate. Background technique [0002] Tedizolid phosphate (tedizolid phosphate, 1), the chemical name is (R)-3-[4-[2-(2-methyltetrazol-5-yl)pyridin-5-yl]-3-fluorophenyl ]-5-Hydroxymethyloxazolidin-2-one phosphate, its structure is, the drug is a prodrug of a new type of oxazolidinone antibacterial drug developed by Cubist Pharmaceuticals, obtained in July 2014 Approved by the FDA for marketing, it has two modes of administration, oral and injection. This product plays a role in the body by removing the phosphate group through the action of serum phosphatase and converting it into the active form of tedizolid. It is mainly used clinically to treat acute bacterial skin and skin tissue structure infections caused by Gram-positive bacteria. Unlike chloramphenicol and lincomycin, this product does not hinder the forma...

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Problems solved by technology

[0003] Because some of the currently reported synthetic processes of tedizolid phosphate have process steps using highly toxic organotin reagents; some involve the use of process steps under ultra-low temperature (-78°C) conditions. There are many products resulting in lower yield, generally lower than 70% purity, generally the purity of tedizolid phosphate obtained after the completion of the reaction is lower than 95%

Another document (new synthesis method of tedizolid phosphate [J] Applied Chemistry 2015, volume 32, issue 11) reported a new process method, using (5R)-3-(4-bromo-3-fluorophenyl )-5-hydroxymethyl oxazolidin-2-one (compound of formula 4) is the starting material, and then with 2-methyl-5-(5-bromopyridin-2-yl) tetrazole (Compound of formula 1) Suzuki coupling, and finally with dibenzyl N, N-diisopropyl phosphoramidite as a phosphorylating reagent, and finally obtain tedizolid phosphate through debenzylation; this method will finally go through hydrogenation reaction to remove Benzyl, there is a big safety hazard

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