869477-96-3

Basic information

• Product Name: BI 1744 hydrochloride
• Synonyms: BI 1744 hydrochloride;Olodaterol hydrochloride;Olodaterol HCl;Olodaterol(BI-1744) HCl;Olodaterol(BI-1744) hydrochloride
• CAS NO: 869477-96-3
• Molecular Formula: C21H27ClN2O5
• Molecular Weight: 422.90248
• Mol File: 869477-96-3.mol
• Article Data: 13

Chemical Properties

• Appearance: /
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: BI 1744 hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: BI 1744 hydrochloride(869477-96-3)
• EPA Substance Registry System: BI 1744 hydrochloride(869477-96-3)

Safety Data

• Hazardous Substances Data: 869477-96-3(Hazardous Substances Data)

Usage

Description

Olodaterol hydrochloride was approved for long-term, oncedaily maintenance treatment of chronic obstructive pulmonary disease (COPD) in 2013 in the following countries: Canada, Russia, United Kingdom, Denmark, and Iceland. The drug has been recommended by a federal advisory panel for approval by the FDA. Developed and marketed by Boehringer Ingelheim, olodaterol is a long-acting b2-adrenergic receptor agonist with high selectivity over the b1- and b3-receptors (219- and 1622-fold, respectively). Upon binding to and activating the b2-adrenergic receptor in the airway, olodaterol stimulates adenyl cyclase to synthesize cAMP, leading to the relaxation of smooth muscle cells in the airway. Administered by inhalation using the Respimat? Soft Mist inhaler, it delivers significant bronchodilator effects within five minutes of the first dose and provides sustained improvement in forced expiratory volume (FEV1) for over 24 h.

Uses

Olodaterol is a long acting β-adrenoceptor agonist used as an inhalation for treating patients with chronic obstructive pulmonary disease (COPD).

Definition

ChEBI: A hydrochloride obtained by combining olodaterol with one equivalent of hydrochloric acid. Used for long-term treatment of airflow obstruction in patients with chronic obstructive pulmonary disease including chronic bronchitis and/or emphysema.

Synthesis

Commercial 20,50-dihydroxyacetophenone (122) was treated with one equivalent of benzyl bromide and potassium carbonate in methylisobutylketone (MIBK) to give the 50-monobenzylated product in 76% yield. Subsequent nitration occurred at the 40-position to provide nitrophenol 123 in 87% yield. Reduction of the nitro group followed by subjection to chloroacetyl chloride resulted in the construction of benzoxazine 124 in 82% yield. Next, monobromination through the use of tetrabutylammonium tribromide occurred at the acetophenone carbon to provide bromoketone 125, and this was followed by asymmetric reduction of the ketone employing ()-DIP chloride to afford an intermediate bromohydrin, which underwent conversion to the corresponding epoxide 126 in situ upon treatment with aqueous NaOH. This epoxide was efficiently formed in 85% yield and 98.3% enantiomeric excess. Epoxide 126 underwent ring-opening upon subjection to amine 127 to provide amino-alcohol 128 in in 84–90% yield and 89.5–99.5% enantiomeric purity following salt formation with HCl. Tertiary amine 127 was itself prepared in three steps by reaction of ketone 129 with methylmagnesium chloride, Ritter reaction of the tertiary alcohol with acetonitrile, and hydrolysis of the resultant acetamide with ethanolic potassium hydroxide. Hydrogenative removal of the benzyl ether within 128 followed by recrystallization with methanolic isopropanol furnished olodaterol hydrochloride (XVI) in 63–70% yield. Overall, the synthesis of olodaterol hydrochloride required 10 total steps (7 linear) from commercially available acetophenone 122.

Upstream product

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• 926319-48-4 6-(phenylmethoxy)-8-[(1R)-1-hydroxy-2-[[2-(4-methoxyphenyl)-1,1-dimethylethyl]amino]ethyl]-2H-1,4-benzoxazin-3(4H)-one hydrochloride 
• 869478-11-5 6-benzyloxy-8-((R)-2-chloro-1-hydroxyethyl)-4H-benzo[1,4]-oxazin-3-one 
• 869478-13-7 6-benzyloxy-8-{(R)-1-hydroxy-2-[2-(4-methoxyphenyl)-1,1-dimethylethylamino]ethyl}-4H-benzo[1,4]oxazin-3-one 
• 124955-27-7 8-(2-hydroxy-2-ethoxyacetyl)-6-(phenylmethoxy)-4H-1,4-benzoxazin-3-one 
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• 926319-53-1 8-(bromoacetyl)-6-(phenylmethoxy)-2H-1,4-benzoxazin-3(4H)-one 
• 35144-39-9 1-(4-methoxyphenyl)-2-methylpropan-2-ol 
• 122-84-9 4-methoxybenzyl methyl ketone 
• 868049-49-4 (R)-6-hydroxy-8-{(1R)-1-hydroxy-2-{[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino}ethyl}-4H-1,4-benzoxazin-3-one 

Relevant articles and documents

Preparation method of olodaterol and salts thereof

The invention relates to a preparation method of olodaterol and salts thereof, which comprises the following steps: in a solvent, carrying out oxidation and nucleophilic addition reaction on a compound shown in a formula I to obtain a compound shown in a

Hydrochloric acid [...] B and its preparation method

The invention relates to a long-acting β2 Adrenal can agonist pharmaceutical hydrochloride crystalline form of [...] B and its preparation method, B and containing said form of the pharmaceutical composition, this crystalline form to its X-ray

A Process for Preparing Olodaterol and Intermediates Thereof

The present invention relates to a process for preparing olodaterol and intermediates thereof. The process comprises of forming compound of Formula 1 by reacting compound of Formula 2 or its acid salt with compound of Formula 3 in the presence of an organ