Preparation method of high-purity tedizolid phosphate

Abstract

The invention discloses a preparation method of high-purity tedizolid phosphate. The preparation method comprises the following steps: 1, with 2-methyl-5-(5-bromopyridin-2-yl)tetrazole as a starting material and tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) as a catalyst, and reacting the starting material and the catalyst with bis(pinacolato)diboron to generate a compound as shown in a formula 1, namely bromine-converted pinacol borate; 2, subjecting a compound shown in a formula 3 and (5R)-3-(4-bromo-3-fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one to Suzuki coupling under the catalyticaction of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) to obtain (R)-3-[4-[2-(2-methyltetrazol-5-yl)pyridin-5-yl]-3-fluorophenyl]-5-one; and 3, preparing tedizolid phosphate from a compound as shown in a formula 5 under the condition of phosphorylation of phosphorus oxychloride.

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, the structure of which is , the drug is a prodrug of a new type of oxazolidinone antibacterial drug developed by Cubist Pharmaceuticals, which was approved by the FDA in July 2014. 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 formati...

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Problems solved by technology

[0003] Since some of the currently reported synthetic processes of tedizolid phosphate have process steps using highly toxic organotin reagents; There are more products resulting in lower yield, generally lower than 70% purity, and the purity of tedizolid phosphate obtained after the general reaction is completed is lower than 95%

Another document (A new method for the synthesis of tedizolid phosphate [J] Applied Chemistry 2015, Volume 32, Issue 11) reported a new process method, using (5R)-3-(4-bromo-3-fluorophenyl )-5-Hydroxymethyloxazolidin-2-one (compound of formula 4) is the starting material. (Compound of formula 1) Suzuki coupling, and finally with dibenzyl N, N-diisopropyl phosphoramidite as a phosphorylating reagent, and finally debenzylized to obtain tedizolid phosphate; the method finally undergoes hydrogenation reaction to remove Benzyl, there is a big safety hazard

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