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

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

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

• 461648-39-5 α,α-diphenyl-1-azabicyclo[2.2.2]octane-4-methanol 
• 1462-37-9 bromoethyl-2-benzyl ether 
• 100-58-3 phenylmagnesium bromide 
• 37586-22-4 4-benzoylpiperidine 
• 195507-51-8 (1-(2-chloroethyl)piperidin-4-yl)(phenyl)methanone 
• 22766-67-2 1-azabicyclo[2.2.2]octane-4-carboxylic acid ethyl ester hydrochloride 
• 100-59-4 phenylmagnesium chloride 
• 498-94-2 isonipecotic acid 
• 26458-74-2 quinuclidin-4-ol 
• 869112-14-1 1-(2-chloroethyl)-4-piperidinecarboxylic acid ethyl ester 
• 1126-09-6 4-carbethoxypiperidine 

Relevant articles and documents

1 - Azabicyclo [2, 2, 2] octan -4 -phenyl ketone compound as well as preparation method and application thereof

The invention provides 1-bicyclic aza[2,2,2]octyl-4-phenyl ketone compound as well as a preparation method and application thereof. Proofed by detection, the structure of the 1-bicyclic aza[2,2,2]octyl-4-phenyl ketone compound is a compound 1. The compound can be used for preparing an umeclidinium bromide medicine for treating COPD (chronic obstructive pulmonary disease), namely that 1-(2-chloroethyl ethyl)-4-benzoyl piperidine is prepared by 4-benzoyl piperidine, and then is subject to ring closing to obtain the compound 1; the compound 1 is further added with a phenyl nucleophilic reagent, and is salted, so as to obtain the umeclidinium bromide. The preparation method has the advantages that the cost is low, the operation is simple and convenient, the preparation method is suitable for industrial production, and the application value is larger. (The formula is shown in the description.).

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

PROCESS FOR THE PREPARATION OF UMECLIDINIUM BROMIDE

The present invention discloses processes comprising a) reacting ethyl isonipecotate with 1 -bromo-2- chloroethane in the presence of an organic base in a solvent to form ethyl 1 -(2-chloroethyl)piperidine- 4-carboxylate (II) or a salt thereof. Process st

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

Convenient new synthesis of umeclidinium bromide

Umeclidinium bromide, a drug used for chronic obstructive pulmonary disease, is synthesized through a new intermediate of phenyl(quinuclidin-4-yl)methanone. This novel method with simple operation flow and cheap reagents, makes it suitable for scale up. The overall four-step process provides umeclidinium bromide in 29% yield and the purity up to 99.83%. The X-ray crystal structure of the drug molecule was first reported.

A PROCESS FOR THE PREPARATION OF UMECLIDINIUM BROMIDE AND INTERMEDIATES THEREOF

Provided herein is a process for the preparation of umeclidinium bromide and intermediates thereof, wherein pure form of umeclidinium bromide is achieved by a two step process under mild conditions.

Novel method for synthesizing umeclidinium bromide

The invention discloses a method for preparing an umeclidinium bromide intermediate compound as shown in a formula 3, and further discloses a synthesizing method of umeclidinium bromide. The synthesizing method effectively avoids unstable phenyl lithium with high price and toxicity, corresponding quinuclidine building reaction steps are omitted, reaction steps are greatly decreased, and reaction efficiency and yield are improved. The synthesizing method is shorter in reaction step, mild in operation condition, high in safety, low in environmental pollution and higher in yield, and a good basisis provided for industrial amplification of the umeclidinium bromide.

Umeclidinium bromide compound

The invention belongs to the technical field of medicines, and specifically relates to anumeclidinium bromide compound. The umeclidinium bromide compound is a long-acting anticholinergic medicine, and has high affinity with a muscarine M1-M5 receptor, and

CHEMICAL PROCESS

The present invention relates to a process for the preparation of umeclidinium bromide, and to processes for preparing intermediates used in the preparation of umeclidinium bromide.