Preparation method of vilanterol

Abstract

The invention provides a preparation method of vilanterol, which comprises the following steps: 1) oxidation reaction: reacting a compound A with an oxidant to obtain a compound B; wherein the oxidantis selenium dioxide; 2) reductive amination reaction: carrying out condensation reaction on the compound B and a compound C to generate an imine intermediate, and carrying out a reaction on the imineintermediate under the action of a reducing agent to obtain a compound D; 3) reduction reaction: carrying out a reaction on the compound D with a chiral catalyst and a reducing agent to obtain a compound E, and 4) ring-opening reaction: performing deprotection ring-opening on the compound E under an acidic condition to obtain vilanterol. The method is advantaged in that the initial raw materialsare easy to obtain, the process is suitable for industrial production, the production yield is high and quality is stable.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to a preparation method of vilanterol. Background technique [0002] Vilanterol is a long-acting beta 2 receptor agonist. The marketed drug is vilanterol triphenylacetate, developed by GlaxoSmithKline. Vilanterol has a fast onset of action and a long duration of action. Studies have found that vilanterol can activate the intracellular adenylate cyclase system, inhibit smooth muscle contraction, and relieve smooth muscle spasm. In vitro experiments showed that compared with formoterol, vilanterol has stronger tissue affinity and higher β 2 Receptor selectivity. Vilanterol is approved for use in several combination drugs, such as Breo Ellipta in combination with fluticasone furoate and Anoro Ellipta in combination with umeclidinium bromide. The FDA approved the use of BreoEllipta in 2013 for the long-term maintenance treatment of airflow obstruction in COPD patients and for the main...

AI Technical Summary

Problems solved by technology

The disadvantage of this method is that chiral β-hydroxylamine compounds are not easy to be synthesized on a large scale, because it is necessary to use azide compound precursor or nitro compound precursor to obtain primary amine through palladium / carbon hydrogen reduction, while sodium azide and nitro Methane is a highly toxic and explosive compound, so this method is not suitable for industrial production, and β-hydroxylamine compounds are relatively active and difficult to separate and purify

At the same time, when preparing side chains with aldehyde groups, pyridine chromium trioxide complexes will be used. Due to their high toxicity and difficult post-reaction treatment, they are not suitable for industrial scale-up production.

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