869113-09-7 Usage
Description
Umeclidinium bromide is a long-acting muscarinic acetylcholine
antagonist developed by GlaxoSmithKline and approved
by the US FDA at the end of 2013 for use in combination with
vilanterol, a b2 agonist, for the treatment of chronic obstructive
pulmonary disease. Due to umeclidinium’s poor oral bioavailability,
the drug is administrated by inhalation as dry powder.
Uses
Umeclidinium Bromide is considered as a potentially long-acting antimuscarinic agent.
Definition
ChEBI: A quaternary ammonium salt that is the bromide salt of umeclidinium. Used in combination with vilanterol for long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 869113-09-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,6,9,1,1 and 3 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 869113-09:
(8*8)+(7*6)+(6*9)+(5*1)+(4*1)+(3*3)+(2*0)+(1*9)=187
187 % 10 = 7
So 869113-09-7 is a valid CAS Registry Number.
869113-09-7Relevant articles and documents
Umerammonium bromide intermediate and preparation method thereof
-
, (2021/03/13)
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
-
Paragraph 0044, (2019/07/16)
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
Convenient new synthesis of umeclidinium bromide
Gu, Jianhui,Zhang, Jie,Wang, Xuan,Wang, Guoping
, p. 995 - 1000 (2018/05/23)
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.
