503068-37-9

Usage

Uses

Used in Pharmaceutical Industry:
(1R)-2-[[6-[2-[(2,6-Dichlorobenzyl)oxy]ethoxy]hexyl]amino]-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)ethanol is used as an impurity in the production of Vilanterol (V260000, Trifenatate), a long-acting β2 adrenergic receptor agonist. It is significant in this context because it contributes to the overall pharmacological profile of Vilanterol, which is utilized for its bronchodilating effects in patients with asthma and chronic obstructive pulmonary disease (COPD). (1R)-2-[[6-[2-[(2,6-Dichlorobenzyl)oxy]ethoxy]hexyl]aMino]-1-(2,2-diMethyl-4H-1,3-benzodioxin-6-yl)ethanol's presence as an impurity may affect the efficacy, safety, and quality control of the final drug product, making it a critical aspect to monitor and manage during the manufacturing process.

Upstream product

• 503068-36-8 (5R)-3-{6-[(2-{[(2,6-dichlorophenyl)methyl]oxy}ethyl)oxy]-hexyl}-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one 
• 208925-08-0 (2R)-hydroxy-2-(2,2-dimethyl-4H-1,3-benzodioxine-6-yl)-ethylamine 
• 15258-73-8 2,6-dichlorobenzyl alcohol 
• 2316-64-5 5-bromo-2-hydroxybenzyl alcohol 
• 52113-69-6 6-bromo-2,2-dimethyl-4H-benzo[1,3]dioxine 
• 503070-57-3 2-((2-((6-bromohexyl)oxy)ethoxy)methyl)-1,3-dichlorobenzene 
• 20443-98-5 2,6-Dichlorobenzyl bromide 
• 452339-73-0 (5R)-5-(2,2-dimethyl- 4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one 
• 452339-72-9 tert-butyl (2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethylcarbamate 
• 452339-71-8 tert-butyl 2-(2,2-dimethyl-4H-1,3-benzodioxane-6-yl)-2-carbonylethylcarbamate 
• 452339-70-7 di-(tert-butyl) 2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethyliminodicarbonate 
• 102293-80-1 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone 
• 54030-34-1 1-(2,2-dimethyl-4H-benzo[d][1,3]dioxan-6-yl)ethanone 

Downstream Products

• 503068-35-7 Vilanterol acetate 
• 503068-34-6 4-[(1R)-2-({6-[(2-{[(2,6-dichlorophenyl)methyl]oxy}ethyl)oxy]-hexyl}-amino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol 
• 503070-58-4 4‐{(1R)‐2‐[(6‐{2‐[(2,6‐dichlorobenzyl)oxy]ethoxy}hexyl)amino]‐1‐hydroxyethyl}‐2‐(hydroxymethyl)phenol triphenylacetate 

Relevant academic research and scientific papers

AN IMPROVED PROCESS FOR PREPARATION OF VILANTEROL OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF

The invention discloses an improved process for preparation of Vilanterol or a pharmaceutically acceptable salt thereof with good yields and high purity.

Preparation method of vilanterol

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.

Preparation method of vilanterol and salt thereof

The invention relates to a preparation method of vilanterol and a salt thereof. The preparation method comprises the following steps: in a solvent, reacting a mixture containing a compound shown as aformula I with succinic acid to obtain a compound shown as a formula II-1; and subjecting the obtained compound shown as the formula II-1 to reacting and conversion to obtain vilanterol and the salt thereof. The preparation method of the vilanterol and the salt thereof has the advantages of higher yield, high purity, easiness in refining, simplicity and convenience in operation and suitability forindustrialization.

BIOCATALYTIC PROCESSES FOR THE PREPARATION OF VILANTEROL

A process for preparing Vilanterol includes a biocatalytic conversion of a ketone substrate to its corresponding alcohol, and then converting the obtained alcohol into Vilanterol. Polypeptides may be used for the biocatalytic conversion of the ketone substrate, such as 2-bromo-l-(2,2-dimethyl-4H-l,3-benzodioxin-6-yl)ethanone, to an enantiopure alcohol, (R)-2-bromo-l-(2,2-dimethyl-4H-l,3-benzodioxin-6-yl)ethanol for the preparation of Vilanterol. Also disclosed is vilanterol tartrate and solid state forms thereof for use as medicaments and for the preparation of other vilanterol salts, or of vilanterol, solid state forms and/or formulations thereof. Also disclosed is a process for the preparation of pharmaceutical formulations including vilanterol tartrate and solid state forms thereof, as well as a method of treating a person suffering from COPD and asthma by administering a therapeutically effective amount of any one or a combination of vilanterol tartrate and solid state forms thereof or a pharmaceutical composition and/or formulation comprising vilanterol tartrate and solid state forms thereof.

A new technology of blue Trowsynthesizes Uygur

The present invention discloses a new method for synthesizing vilanterol. The present invention provides a completely-new vilanterol synthesis method, wherein the easily available starting raw material is adopted so as to effectively avoid disadvantages of harsh reaction conditions (such as anhydrous reaction), expensive reagents and the like of the existing process, and the method has characteristics of short route, high yield, and market competitiveness.

PROCESS FOR THE PREPARATION OF VILANTEROL AND INTERMEDIATES THEREOF

An improved process for the preparation of vilanterol and pharmaceutically acceptable salts thereof is disclosed. More specifically the improved process for preparing intermediates for the preparation of vilanterol is disclosed.

Synthesis and structure-activity relationships of long-acting β2 adrenergic receptor agonists incorporating metabolic inactivation: An antedrug approach

A series of saligenin β2 adrenoceptor agonist antedrugs having high clearance were prepared by reacting a protected saligenin oxazolidinone with protected hydroxyethoxyalkoxyalkyl bromides, followed by removal of the hydroxy-protecting group, alkylation, and final deprotection. The compounds were screened for β2, β1, and β3 agonist activity in CHO cells. The onset and duration of action in vitro of selected compounds were assessed on isolated superfused guinea pig trachea. Compound 13f had high potency, selectivity, fast onset, and long duration of action in vitro and was found to have long duration in vivo, low oral bioavailability in the rat, and to be rapidly metabolized. Crystalline salts of 13f (vilanterol) were identified that had suitable properties for inhaled administration. A proposed binding mode for 13f to the β2-receptor is presented.