320347-97-5

Usage

Uses

(R)-3-Quinuclidinyl di(2-thienyl)glycolate acts as a potent and long-acting muscarinic antagonist with minimal systemic exposure after inhalation. Used in the treatment of chronic obstructive pulmonary disease.

Upstream product

• 26447-85-8 hydroxy-di-thiophen-2-yl-acetic acid methyl ester 
• 25333-42-0 (R)-quinuclidin-3-ol 
• 28569-88-2 Ethyl (2,2'-Dithienyl)glycolate 
• 4746-63-8 2-hydroxy-2,2-di(thiophen-2-yl)acetic acid 
• 1003-09-4 2-bromothiophene 
• 27998-36-3 2,2-di(2-thiophenyl)-2-hydroxyethanoic acid-3-quinine ester 
• 1619-34-7 3-quinuclidinol 
• 59653-40-6 (+)-Aceclidine 

Downstream Products

• 1195981-90-8 (R)-3-(2-hydroxy-2,2-dithiophen-2-yl-acetoxy)-1-(5-phenylisoxazol-3-ylmethyl)-1-azoniabicyclo[2.2.2]octane chloride 
• 867022-63-7 aclidinium bromide 
• 320345-88-8 (3R)-3-{[hydroxy(di-2-thienyl)acetyl]oxy}-1-(2-phenylethyl)-1-azoniabicyclo[2.2.2]octane bromide 
• 1185907-26-9 (3R)-1-benzyl-3-{[hydroxy(di-2-thienyl)acetyl]oxy}-1-azoniabicyclo[2.2.2]octane bromide 
• 320345-91-3 (3R)-3-{[hydroxy(di-2-thienyl)acetyl]oxy}-1-(4-phenylbutyl)-1-azoniabicyclo[2.2.2]octane bromide 
• 320345-99-1 aclidinium bromide 

Relevant academic research and scientific papers

A PROCESS FOR PREPARING ACLIDINIUM BROMIDE AND INTERMEDIATES THEREOF

Provided herein is a process for synthesis of aclidinium bromide and intermediates thereof, wherein the process for the preparation of aclidinium bromide increases the % yield of aclidinium bromide by about 70% to 90%.

Choline M receptor anti-caking agent re-crystallization method

The invention provides a choline M receptor anti-caking agent re-crystallization method, which comprises: (1) heating an aclidinium bromide crude product and DMF to a temperature of 90-130 DEG C, stirring, dissolving, and clarifying; (2) cooling the solut

Preparation method of quinine-3-yl R-2,2-di(2-thienyl)-2-glycolate

The invention discloses a preparation method of quinine-3-yl R-2,2-di(2-thienyl)-2-glycolate, and belongs to the technical field of preparation and application of an anti-chronic obstructive pulmonarydisease drug aclidinium bromide intermediate. The preparation method comprises the following steps: adding methyl 2,2-dithienylglycolate, R-(-)-3-quinuclidinol and sodium methoxide into an organic solvent in an inert gas atmosphere, and carrying out a heating reaction; and adding the obtained reaction solution into a diluted acid solution after the reaction is finished, separating the obtained water layer, alkalizing the water layer, and filtering the alkalinized water layer to obtain the quinine-3-yl R-2,2-di(2-thienyl)-2-glycolate. The preparation method of the quinine-3-yl R-2,2-di(2-thienyl)-2-glycolate has the advantages of simplicity in operation, high yield, mild conditions, few three wastes, and easiness in industrial production.

Novel method for synthesis and purification of aclidinium bromide

The invention discloses a novel method for synthesis and purification of aclidinium bromide. According to the method, tetrahydrofuran is used, haloalkane is used as an initiator, and a finished product is obtained through solvent extraction and recrystall

High-purity high-yield aclidinium bromide preparation method suitable for industrial production

The invention discloses a high-purity high-yield aclidinium bromide preparation method suitable for industrial production. The preparation method comprises the following steps: 1) adding methyl 2,2-di(2-thienyl)-2-hydroxyacetate and TBDMSCl into solvent,

A 2, 2 - di thienyl -2 - hydroxy acetic acid - R - quinine -3 - base esterification composition and its preparation method

The invention relates to a 2,2-dithienyl-2-hydroxycaproic acid-R-quinine-3-ester compound and a preparation method thereof. The structure of the compound is shown in the specification. The preparation method comprises the following steps: performing reflux reaction to methyl chlorooxoacetate, quinuclidinol and a base in a solvent, and separating and purifying to obtain a substance A; adding 1/10-3/10 2-bromothiophene and magnesium powder, adding iodine to initiate reaction, then dropwise adding 2-bromothiophene, stirring at room temperature for 30min-1h after the dropwise addition is finished, then adding the substance A, stirring and reacting for 30min at room temperature, then stirring and reflux-reacting for 4-8h, to obtain the 2,2-dithienyl-2-hydroxycaproic acid-R-quinine-3-ester compound. According to the 2,2-dithienyl-2-hydroxycaproic acid-R-quinine-3-ester compound and the preparation method thereof, the reaction operations are simple, the yield is high, the price is low, the reaction route is short, three wastes are fewer, and the industrial production is easy.

Discovery of Novel Potent Muscarinic M3 Receptor Antagonists with Proper Plasma Stability by Structural Recombination of Marketed M3 Antagonists

The marketed long-acting M3 antagonists for treatment of chronic obstructive pulmonary disease have inappropriate plasma stability (either overstable or excessively unstable), which causes substantial systemic exposure or poor patient compliance. To discover novel M3 antagonists with proper plasma stability, we synthesized and biologically evaluated a series of chiral quaternary ammonium salts of pyrrolidinol esters, which were designed by structural recombination of the marketed M3 antagonists. As a result, two novel potent M3 antagonists, (R/S)-3-[2-hydroxy-2,2-di(thiophen-2-yl)acetoxy]-1,1-dimethylpyrrolidinium bromides (1 a: Ki=0.16 nm, IC50=0.38 nm, t1/2=9.34 min; 1 b: Ki=0.32 nm, IC50=1.01 nm, t1/2=19.2 min) with proper plasma stability were identified, which (particularly 1 a) hold great promise as clinical drug candidates to overcome the drawbacks caused by the inappropriate stability of the currently marketed M3 antagonists. In addition, structure–activity relationship studies revealed that the R configuration of the pyrrolidinyl C3 atom was clearly better than the S configuration.

A choline M receptor antagonists arab League bromine ammonium and its preparation method

The invention relates to choline M receptor antagonist aclidinium bromide and a preparation method thereof. The chemical structural formula of the choline M receptor antagonist aclidinium bromide is as shown in the specification. The preparation method comprises the following steps: mixing R-quinine-3 alcohol, alkali and an organic solvent, dripping methyl oxalyl chloride, after the methyl oxalyl chloride is completely dripped, heating, performing heating reflux for 1-20 hours, and separating and purifying, thereby obtaining a substance A; adding iodine into a tetrahydrofuran solution of 2-bromothiophene and magnesium powder to initiate reaction for 1-5 hours, thereby preparing a Grignard reagent of 2-bromothiophene, adding the substance A, stirring to react for 10-30 minutes at the room temperature, performing heating reflux for 4-6 hours, separating and purifying, thereby preparing 2,2-dithienyl-2-glycolic acid-R-quinine-3-base ester, and performing quaterisation reaction with 3-phenoxypropyl bromine, thereby obtaining aclidinium bromide. The aclidinium bromide provided by the invention is simple in reaction operation, high in yield, low in price, short in reaction route, small in waste generation and easy in industrialization production.

AN ADVANTAGEOUS PROCESS FOR PREPARING 1-AZONIABICYCLO[2.2.2]OCTANE,3-[(HYDROXYDI-2-THIENYLACETYL)OXY]-1-(3?PHENOXYPROPYL)-, BROMIDE, (3R)- AND ITS NOVEL CRYSTALLINE FORM-I

The present invention discloses the process for preparation of 1- ?Azoniabicyclo[2.2.2]octane,3-[(hydroxydi-2-thienylacety1)oxy]-1-(3?iphenoxypropy1)-, bromide, (3R)- and its novel crystalline form-I

Choline M receptor antagonist aclidinium bromide and preparation method thereof

The invention relates to choline M receptor antagonist aclidinium bromide and a preparation method thereof. According to the preparation method, 2,2-di(2-thienyl)-2-methyl glycolate reacts with 3-quinuclidinol to obtain 2-hydroxy-2,2-di(2-thienyl) acetic