753498-25-8

Usage

Uses

Used in Pharmaceutical Industry:
Indacaterol Maleate is used as a long-acting β2 adrenoreceptor agonist for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It works by relaxing and opening the airways in the lungs, making it easier for patients to breathe. This application is particularly beneficial for individuals suffering from respiratory conditions, as it helps to alleviate symptoms and improve their overall quality of life.
Used in COPD Treatment:
Indacaterol Maleate is used as a bronchodilator for the treatment of chronic obstructive pulmonary disease (COPD). It helps to reduce inflammation and constriction of the airways, allowing for easier breathing and improved lung function. This application is crucial in managing the symptoms of COPD, which can be debilitating and significantly impact a patient's daily life.

Clinical Use

Indacaterol is a b-adrenoceptor agonist currently approved in Europe as Onbrez, and is marketed by Novartis. It needs to be taken only once a day, unlike competitors formoterol and salmeterol. These drugs are used in the treatment of chronic obstructive pulmonary disease (COPD) and asthma. Onbrez is administered via an aerosol formulation through a dry powder inhaler. A Phase III trial published in July 2010 suggested that indacaterol is significantly more effective than twice-daily formoterol in improving FEV1 and reduces the need for rescue medication.

Synthesis

The synthesis of indacaterol relies on the union of the dihydroindeneamine region and the quinolinol region of the molecule. Preparation of the dihydroindene unit of indacaterol was reported by researchers at Novartis in 2006 and is summarized in the scheme. 2,3-Dihydro-1H-inden-2-amine (59) was protected as its trifluoroacetamide 61 and was followed by Friedel–Crafts alkylation with acetylchloride to give 62. Hydrogenative carbonyl reduction of this unsymmetrical dihydroindene provided amide 63. An iterative Friedel–Crafts acylation/hydrogenation sequence was used to install the second ethyl group, giving rise to trifluoroacetamide 64. Basic hydrolysis to remove the trifluoroacetamide functionality, followed by salt formation by means of gaseous HCl furnished the dihydroindene amine 65. The synthesis of the remaining portion of the molecule starts from 8-hydroxyquinoline (66). Friedel–Crafts alkylation with acetylchloride and trichloroaluminum installed the acetophenone functionality at the 5-position of the quinoline frame followed by benzyl protection of the hydroxyl group to give ether 67. Oxidation of quinoline 67 with mCPBA and acylation of the resulting N-oxide with acetic anhydride and thermal rearrangement produced quinolone 68. Bromination of the methyl ketone and subsequent asymmetric reduction provided (R)-alcohol 69. Bromohydrin 69 was then converted to the epoxide using potassium carbonate prior to amination of the epoxide with dihydroindene intermediate 65 to furnish the indacaterol skeleton 70. Hydrogenolytic debenzylation and maleate salt formation provided indacaterol maleate (XI).

Upstream product

• 753498-41-8 5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one benzoate 
• 110-16-7 maleic acid 
• 312753-79-0 N-benzyl-5,6-diethyl-2,3-dihydro-1H-inden-2-amine 
• 774222-23-0 5-(R)-(2-amino-1-hydroxy-ethyl)-8-phenylmethoxy-(1H)-quinolin-2-one 
• 62978-73-8 5-acetyl-8-hydroxy-2(1H)-quinolinone 
• 93609-84-8 5-acetyl-8-benzyloxy-1H-quinolin-2-one 
• 312753-53-0 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride 
• 312753-06-3 indacaterol 
• 110-17-8 (2E)-but-2-enedioic acid 
• 435273-75-9 (R)-8-(benzyloxy)-5-[2-[(5,6-diethyl-2,3-dihydro-1H-indole-2-yl)amino]-1-hydroxyethyl]quinolin-2(1H)-one 
• 1384188-70-8 (R)-5-[2-(5,6-diethyl-indan-2-yl)ammo-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one hydrochloride 
• 312753-70-1 5,6-diethyl-2,3-dihydro-1H-inden-2-amine 
• 173140-90-4 (R)-5-(2-oxiranyl)-8-benzyloxy-2(1H)-quinolinone 

Relevant academic research and scientific papers

INHALABLE FORMULATION OF A SOLUTION CONTAINING INDACATEROL MALEATE AND GLYCOPYRRONIUM BROMIDE

The present invention discloses a liquid, propellant-free pharmaceutical preparation and a method for administering a pharmaceutical preparation by nebulizing the pharmaceutical preparation in an inhaler. The propellant-free pharmaceutical preparation comprising: (a) active substances selected from glycopyrronium bromide and indacaterol maleate; (b) a solvent; and (c) a pharmacologically acceptable preservative, optionally including a pharmacologically acceptable stabilizer, a pharmacologically acceptable solubilizing agent, a pharmacologically acceptable co-solvent, or other pharmacologically acceptable additives.

IMPROVED PROCESS FOR THE PREPARATION OF INDACATEROL MALEATE

An improved process for the preparation of Indacaterol Maleate having the structural formula (I). The present invention also relates to an improved process for the preparation of benzyl intermediate of Formula IV. The present invention provides improved p

Preparation method of indacaterol and salt thereof

The invention relates to a preparation method of indacaterol and a salt thereof. The preparation method comprises the following steps: in a solvent, reacting a mixture containing a compound as shown in a formula I with m-chlorobenzoic acid to obtain a com

A maleic acid yin dutrow intermediate and its preparation and use

The invention relates to maleic acid yin dutrow intermediate (R)- 8 - (benzyloxy) - 5 - [2 - [(5, 6 - diethyl - 2, 3 - dihydro - 1 H - indene - 2 - yl) amino] - 1 - hydroxy ethyl] quinoline - 2 (1 H) - one a new salt and its crystalline form, the salt and its crystalline form has good impurity removing effect and thermodynamic stability, the preparation method is simple, the operation is facilitated and the storage, is suitable for industrial application. The invention also relates to the new salt and its crystal preparation method, and process for the preparation of maleic acid yin dutrow use.

Preparation method for indacaterol or salt thereof

The invention relates to a preparation method for indacaterol or a salt thereof. According to the method, hydrogen diluted by inert gas is selected and used as a hydride source, and high-purity indacaterol maleate is prepared under metal catalysis conditions.

Preparation method for indacaterol maleate

The invention specifically relates to a preparation method for indacaterol maleate, belonging to the field of drug synthesis. The preparation method is simple and short in steps, easy to operate, safe, friendly to environment and fee of an alkaline solution; after a heating reaction, a coupled product in the step 1) can be obtained, and the amount of produced regioisomers, dimers and other by-products is small; the yield of the product indacaterol maleate is high, as high as 93%, and the HPLC purity of the product indacaterol maleate is more than 97.8%; post-treatment is simple, and industrialproduction of indacaterol maleate is facilitated; and the product indacaterol maleate is high in optical purity.

A Process for Preparing Indacaterol and Salts Thereof

The present invention relates to a process for preparing indacaterol or salts thereof. The process comprises of forming compound of Formula 1 by reacting compound of Formula 2 and compound of Formula 3 in the presence of a solvent to Form compound of Formula 4, which on removal of the protecting groups forms compound of Formula 1.

MIXED SOLVATE OF (R)-5-[2-(5,6-DIETHYLINDAN-2-YLAMINO)-1-HYDROXYETHYL] -8-HYDROXY-1H-QUINOLIN-2-ONE L-TARTRATE

The present invention provides an improved process for the manufacture of indacaterol or a pharmaceutically acceptable salt thereof, preferably indacaterol maleate, in high chemical and enantiomeric purity and high yield, via a mixed solvate of (R)-5-[2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one L-tartrate salt, compound of formula (II).

Novel Process for Preparation of Indacaterol or Its Pharmaceutically Acceptable Salts

A novel process the for preparation of Indacaterol or its pharmaceutically acceptable salts and novel intermediates employed in the preparation thereof that is economically significant for large scale.

dutrow[...][...] method for the synthesis of intermediates

Disclosed is an intermediate for synthesizing indacaterol, having a structure represented by formula IV. Also disclosed are a method for synthesizing the indacaterol intermediate and a method for synthesizing indacaterol by using the intermediate. During synthesis of indacaterol, the intermediate of formula IV is reduced to obtain a chiral or racemic compound, which is then debenzylated to obtain indacaterol or a raceme thereof. By using the compound of formula IV as an intermediate for synthesizing indacaterol, the present invention provides a new route for synthesizing indacaterol, and avoids various byproducts produced in the process of synthesizing indacaterol using conventional methods.