869113-09-7

Basic information

• Product Name: Umeclidinium bromide
• Synonyms: Umeclidiniu;diphenyl-[1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-4-yl]methanol;Umeclidinium bromide, >=98%;Umeclidinium(GSK573719A);Jmechlidinium bromide;1-Azoniabicyclo[2.2.2]octane;1-(2-(benzyloxy)ethyl)-4-(hydroxydiphenylmethyl)quinuclidin-1-ium bromide;1-Azoniabicyclo[2.2.2]octane, 4-(hydroxydiphenylMethyl)-1-[2-(phenylMethoxy)ethyl]-, broMide (1:1)
• CAS NO: 869113-09-7
• Molecular Formula: C29H34BrNO2
• Molecular Weight: 508.48976
• EINECS: 1592732-453-0
• Product Categories: API
• Mol File: 869113-09-7.mol
• Article Data: 12

Chemical Properties

• Appearance: /
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly), Water (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: Umeclidinium bromide(CAS DataBase Reference)
• NIST Chemistry Reference: Umeclidinium bromide(869113-09-7)
• EPA Substance Registry System: Umeclidinium bromide(869113-09-7)

Safety Data

• Hazardous Substances Data: 869113-09-7(Hazardous Substances Data)

Usage

Description

Umeclidinium bromide is a long-acting muscarinic acetylcholine antagonist developed by GlaxoSmithKline and approved by the US FDA in 2013 for use in combination with vilanterol, a β2 agonist, for the treatment of chronic obstructive pulmonary disease (COPD). It is a quaternary ammonium salt that is the bromide salt of umeclidinium, characterized by its poor oral bioavailability and is therefore administered by inhalation as dry powder.

Uses

Used in Pharmaceutical Industry:
Umeclidinium bromide is used as a long-acting antimuscarinic agent for the long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). It helps to improve lung function and reduce symptoms associated with the condition.
Used in Respiratory Therapy:
Umeclidinium bromide is used as a bronchodilator in combination with vilanterol to manage and alleviate symptoms of COPD, such as shortness of breath and wheezing. This combination therapy aims to provide effective control of the disease and improve the quality of life for patients.

Synthesis

Commercially available ethyl isonipecotate (278) was alkylated with 1-bromo-2-chloroethane in the presence of K2CO3 in acetone to give ethyl 1-(2-chloroethyl)piperidine-4-carboxylate (279). This material was then treated with lithium diisopropylamine (LDA) in THF to affect a transannular substitution reaction resulting in the cyclized quinuclidine 280 in 96% yield. Excess of phenyllithium was added to ester 280 in THF starting at low temperature then gradually warming to room temperature to give tertiary alcohol 281 in 61% yield. Amine 281 was finally alkylated with benzyl 2- bromoethyl ether (282) in MeCN/CHCl3 at elevated temperatures to afford umeclidinium bromide (XXXV) in 69% yield.

references

[1] salmon m, luttmann m a, foley j j, et al. pharmacological characterization of gsk573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. journal of pharmacology and experimental therapeutics, 2013, 345(2): 260-270.

Upstream product

• 1126-09-6 4-carbethoxypiperidine 
• 591-51-5 phenyllithium 
• 869112-14-1 1-(2-chloroethyl)-4-piperidinecarboxylic acid ethyl ester 
• 100-58-3 phenylmagnesium bromide 
• 37586-22-4 4-benzoylpiperidine 
• 195507-51-8 (1-(2-chloroethyl)piperidin-4-yl)(phenyl)methanone 
• 1462-37-9 bromoethyl-2-benzyl ether 
• 22766-67-2 1-azabicyclo[2.2.2]octane-4-carboxylic acid ethyl ester hydrochloride 
• 498-94-2 isonipecotic acid 
• 100-59-4 phenylmagnesium chloride 
• 461648-39-5 α,α-diphenyl-1-azabicyclo[2.2.2]octane-4-methanol 

Relevant articles and documents

Umerammonium bromide intermediate and preparation method thereof

The invention relates to an umerammonium bromide intermediate and a preparation method thereof. The preparation method comprises the following steps: performing esterification, condensation, substitution, cyclization, addition and the like on isopiperidine acid to obtain a target compound. Compared with the existing preparation method, the method has the advantages that the yield of the compound shown as the formula VII is high, the content of the impurity 1 is remarkably reduced, and a process guarantee is provided for industrially preparing high-purity umequat bromide, and thus the medication safety of medicines is guaranteed.

Umeclidinium bromide intermediate crystal form as well as preparation method thereof and method for preparing umeclidinium bromide from intermediate

The invention relates to a umeclidinium bromide intermediate (1-azabicyclo[2.2.2]octan-4-yl)(diphenyl)methanol acid salt (II) and a preparation method thereof, relates to a compound (1-azabicyclo[2.2.2]octan-4-yl)(diphenyl)methanol hydrochloride (V) cryst

A More Sustainable Process for Preparation of the Muscarinic Acetylcholine Antagonist Umeclidinium Bromide

A more sustainable process for the synthesis of the long-acting muscarinic acetylcholine antagonist umeclidinium bromide is described. Specifically, we report the synthesis of ethyl 1-(2-chloroethyl)-4-piperidinecarboxylate, a key intermediate in the prep