869477-96-3

Usage

Uses

Used in Pharmaceutical Industry:
BI 1744 hydrochloride is used as a long-acting β2-adrenergic receptor agonist for treating patients with chronic obstructive pulmonary disease (COPD). It helps to relax smooth muscle cells in the airway, leading to improved lung function and reduced symptoms of COPD.

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

• 781614-25-3 6-benzyloxy-8-{(R)-1-hydroxy-2-[2-(4-methoxy-phenyl)-1,1-dimethyl-ethylamino]-ethyl}-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 
• 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 
• 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 
• 122-84-9 4-methoxybenzyl methyl ketone 
• 35144-39-9 1-(4-methoxyphenyl)-2-methylpropan-2-ol 
• 926319-53-1 8-(bromoacetyl)-6-(phenylmethoxy)-2H-1,4-benzoxazin-3(4H)-one 
• 124955-27-7 8-(2-hydroxy-2-ethoxyacetyl)-6-(phenylmethoxy)-4H-1,4-benzoxazin-3-one 
• 56490-93-8 1,1-dimethyl-2-(4-methoxyphenyl)ethylamine hydrochloride 
• 869478-11-5 6-benzyloxy-8-((R)-2-chloro-1-hydroxyethyl)-4H-benzo[1,4]-oxazin-3-one 

Relevant academic research and scientific papers

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

Crystal form C of olodaterol hydrochloride and preparation method thereof

The invention relates to a crystal form C of a long-acting beta2 adrenergic agonist olodaterol hydrochloride and a preparation method thereof and a pharmaceutical composition containing the crystal form C. The crystal form is represented by the characteri

IMPROVED PROCESS FOR THE MANUFACTURE OF R-6-HYDROXY-8-[1-HYDROXY-2-[2-(4-METHOXYPHENYL)-1,1-DIMETHYLETHYLAMINOETHYL]-2H-1,4-BENZOXAZIN-3(4H)-ONE HYDROCHLORIDE

The present invention provides an improved process for the manufacture (R)-6- hydroxy-8-[1-hydroxy-2-[2-(4-methoxyphenyl)-1,1-dimethyl-ethylamino-ethyl]-2H-1,4- benzoxazin-3(4H)-one, in high purity and high yield, through the use of 1,1-dimethyl-2- (4-met

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

PROCESS FOR THE MANUFACTURING OF BETA MIMETICS

The invention relates to a method for producing betamimetics of formula (1), wherein in which n represents 1 or 2; R1 represents hydrogen, halogen, C1-4-alkyl or O—C1-4-alkyl; R2 represents hydrogen, halogen, C

Discovery of olodaterol, a novel inhaled β2-adrenoceptor agonist with a 24 h bronchodilatory efficacy

Compound 4p was identified from a series of 6-hydroxy-4H-benzo[1,4]oxazin-3-ones as potent agonist of the human β2-adrenoceptor with a high β1/β2-selectivity. A complete reversal of acetylcholine-induced bronchoconstrictio

PROCESS FOR THE MANUFACTURING OF BETAMIMETICS

The present invention relates to a process for preparing betamimetics of formula 1, wherein n denotes 1 or 2; R1 denotes hydrogen, halogen, C1-4-alkyl or O—C1-4-alkyl; R2 denotes hydrogen, halogen, C1-4/su

Novel medicaments for the treatment of respiratory diseases

The present invention relates to the use of the compounds of general formula 1 wherein the groups R1, R2 and R3 may have the meanings given in the claims and in the specification, for preparing a pharmaceutical composition

New enentiomerically pure beta agonists, process for the manufacture thereof and use thereof as medicaments

The present invention relates to enantiomerically pure compounds of general formula 1 wherein the groups R1, R2, R3, R4 and X? may have the meanings given in the claims and in the specification, proce