67346-49-0

Basic information

• Product Name: (R,R)-Formoterol
• Synonyms: N-[2-hydroxy-5-[(1R)-1-hydroxy-2-[[(2R)-1-(4-methoxyphenyl)propan-2-yl]amino]ethyl]phenyl]formamide;4-[(1R)-2-[[(1R)-2-(4-Methoxyphenyl)-1-methylethyl]amino]-1-hydroxyethyl]-2-(formylamino)phenol;N-[2-Hydroxy-5-[(1R)-1-hydroxy-2-[[(αR)-α-methyl-4-methoxyphenethyl]amino]ethyl]phenyl]formamide;N-[2-Hydroxy-5-[(R)-1-hydroxy-2-[[(R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]formamide;Arformoterol;(R,R)-Formoterol;Formamide, N-[2-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]-;Formamide, N-[2-hydroxy-5-[1-hydroxy-2-[[2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]-, [R-(R*,R*)]-
• CAS NO: 67346-49-0
• Molecular Formula: C19H24N2O4
• Molecular Weight: 344.4049
• Mol File: 67346-49-0.mol
• Article Data: 17

Chemical Properties

• Boiling Point: 603.2°Cat760mmHg
• Flash Point: 318.6°C
• Appearance: /
• Density: 1.233g/cm³
• Refractive Index: 1.604
• CAS DataBase Reference: (R,R)-Formoterol(CAS DataBase Reference)
• NIST Chemistry Reference: (R,R)-Formoterol(67346-49-0)
• EPA Substance Registry System: (R,R)-Formoterol(67346-49-0)

Safety Data

• Hazardous Substances Data: 67346-49-0(Hazardous Substances Data)

Usage

Description

Arformoterol, a selective long-acting b2-agonist, was launched as an inhalation solution for treatment of bronchoconstriction associated with COPD. It is the active (R,R)-enantiomer of the previously marketed b2-agonist formoterol, which is registered as a racemic mixture. Similar to other b2-agonists, the mechanism of action of formoterol and arformoterol involves activation of adenyl cyclase, leading to increased production of cyclic adenosine monophosphate (cAMP) via ATP. Increased levels of intracellular cAMP result in relaxation of the bronchial smooth muscle, and also prevent mast cells from releasing inflammatory mediators. Arformoterol has high binding affinity for the human b2 receptor (Kd 2.9 nM) and approximately 39-fold selectivity over the b1 receptor (Kd 113 nM). It is W1,000 times more potent b2 ligand than the corresponding (S,S)-enantiomer (Kd 3100 nM), and twice as potent as racemic formoterol (Kd 5.2 nM). Additionally, arformoterol acts as a full or nearly full agonist of the b2 receptor, whereas the (S,S)-enantiomer acts as an inverse agonist. Therefore, the (R,R)-enantiomer may account exclusively for the activation of b2 receptors by the racemic mixture.

Uses

(R,R)-Formoterol (Arformoterol) (CAS# 67346-49-0) is aused in the methods for treating chronic obstructive pulmonary disease by administration of a bronchodilator using a nebulizer.

Definition

ChEBI: An N-[2-hydroxy-5-(1-hydroxy-2-{[1-(4-methoxyphenyl)propan-2-yl]amino}ethyl)phenyl]formamide in which both of the stereocentres have R configuration. The active enantiomer of formoterol, it is administered by inhalation generally as the tartrate salt) as a direct-acting sympathomimetic and bronchodilator for the treatment of chronic obstructive pulmonary disease (any progressive respiratory disease that makes it harder to breathe over time, such as chronic bronchitis and emphysema).

Brand name

Brovana

InChI:InChI=1/C20H25NO4/c1-14(11-15-4-7-17(25-2)8-5-15)3-9-19(23)16-6-10-20(24)18(12-16)21-13-22/h4-8,10,12-14,19,23-24H,3,9,11H2,1-2H3,(H,21,22)/t14-,19-/m0/s1

Upstream product

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• 1198769-18-4 (R)-4-benzyloxy-3-nitro-α-(N-benzyl-N-(1-methyl-2-p-methoxyphenylethyl)amino)acetophenone 

Relevant articles and documents

Preparation method and application of formoterol and medicinal salt thereof

The invention provides a preparation method and application of formoterol and medicinal salt thereof, and relates to the technical field of chemical synthesis. The preparation method of formoterol comprises the following steps: reacting a compound shown as a formula I under the action of a palladium-containing catalyst, a hydrogen donor and an alkali reagent to obtain a compound shown as a formulaII, wherein the hydrogen donor is a combination of formic acid and ammonium formate. The compound shown in the formula I contains O-benzyl, N-benzyl, formyl and methoxyl at the same time, hydrogen can be slowly and continuously generated under the action of a palladium-containing catalyst by adopting the combination of a hydrogen donor and an alkali reagent, a method for directly introducing hydrogen in the conventional technology is replaced, benzyl of O-benzyl and N-benzyl on the compound shown in the formula I can be removed, formyl and methoxyl are not affected, the yield and purity of the product are guaranteed, reaction conditions are mild, technological operation is safe and easy to control, and the method is simple, convenient and easy to implement and suitable for large-scale production.

PROCESS FOR THE PREPARATION OF ARFORMOTEROL OR SALT THEREOF

Provided is an improved process for the preparation of arformoterol L-(+)-tartrate, and more specifically provided is a novel process for the preparation of arformoterol L-(+)-tartrate via arformoterol D-(?)-tartrate.

Process for preparation of intermediates of arformoterol

An improved method for the preparation of optically pure isomers of Formoterol is disclosed, particularly the (R,R)-isomer.A method of preparation of substantially enantiomerically pure (R,R)-1-(4-Benzyloxy-3-nitro-phenyl)-2-[[2-(4-methoxy-phenyl)-1-methyl-ethyl]-(1-phenyl-ethyl)-amino]-ethanol to use in the production of (R,R)-Formoterol is also disclosedAn improved method for the preparation of optically pure isomers of Formoterol is disclosed, particularly the (R,R)-isomer. A method of preparation of substantially enantiomerically pure (R,R)-1-(4-Benzyloxy-3-nitro-phenyl)-2-[[2-(4-methoxy-phenyl)-1-methyl-ethyl]-(1-phenyl-ethyl)-amino]-ethanol to use in the production of (R,R)-Formoterol is also disclosed