Olodaterol

Base Information

• Chemical Name: Olodaterol
• CAS No.: 868049-49-4
• Molecular Formula: C21H26N2O5
• Molecular Weight: 386.448
• European Community (EC) Number: 813-858-3
• UNII: VD2YSN1AFD
• ChEMBL ID: CHEMBL605846
• DSSTox Substance ID: DTXSID601024792
• Metabolomics Workbench ID: 152134
• NCI Thesaurus Code: C170249
• Nikkaji Number: J3.100.561B
• Pharos Ligand ID: ZX6UH2HDUTHB
• RXCUI: 1546059
• Wikidata: Q7088466
• Wikipedia: Olodaterol
• Mol file: 868049-49-4.mol

Synonyms:6-hydroxy-8-(1-hydroxy-2-((2-(4-methoxyphenyl)-1,1-dimethylethyl)amino)ethyl)-2H-1,4-benzoxazin-3(4H)-one;BI 1744 CL;BI-1744 CL;olodaterol;Striverdi Respimat

Chemical Property of Olodaterol

Chemical Property:

• Boiling Point: 649.05 °C at 760 mmHg
• PKA: 9.42±0.20(Predicted)
• Flash Point: 346.333 °C
• PSA: 103.54000
• Density: 1.251 g/cm³
• LogP: 2.85200
• XLogP3: 1.8
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 7
• Exact Mass: 386.18417193
• Heavy Atom Count: 28
• Complexity: 521

Purity/Quality:

99%, ^*data from raw suppliers

Olodaterol >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)(CC1=CC=C(C=C1)OC)NCC(C2=C3C(=CC(=C2)O)NC(=O)CO3)O
• Isomeric SMILES: CC(C)(CC1=CC=C(C=C1)OC)NC[C@@H](C2=C3C(=CC(=C2)O)NC(=O)CO3)O
• Recent ClinicalTrials: ANTES B+ Clinical Trial
• Recent EU Clinical Trials: A 4-week, randomised, double-blind, parallel group study to evaluate the efficacy and safety of tiotropium + olodaterol fixed dose combination (5/5 μg) delivered by the Respimat? inhaler versus the free combination of tiotropium 5 μg and olodaterol 5 μg delivered by separate Respimat? inhalers in patients with chronic obstructive pulmonary disease (COPD)
• Recent NIPH Clinical Trials: A randomized prospective controlled trial of long-acting muscarinic antagonist and long-acting be-ta2 agonist fixed dose combinations in patients with chronic obstructive pulmonary disease: Effects on quality of life and pulmonary function and preference
• Description: In 2013, olodaterol (also known BI-1744 CL) was approved for the treatment of chronic obstructive pulmonary disease (COPD) in Russia (March), Canada (June), and the EuropeanUnion (October). Olodaterol is delivered via the Respimat? Soft Mist? inhaler. Olodaterol was discovered from an effort to identify a β2-adrenergic receptor agonist that could be given once daily and with a superior safety profile over known β2- adrenergic receptor agonists. Olodaterol is a potent β2 agonist (EC50=0.1 nM, intrinsic activity=88%) and is highly selective for the β2 receptor over β1 and β3 receptors. In preclinical models in guinea pigs and dogs, olodaterol had a rapid onset of action and provided bronchoprotection over 24 h. Mechanistic studies indicated that olodaterol forms a highly stable complex with the β2-adrenergic receptor, with a dissociation half-life of 17.8 h. The synthesis of olodaterol proceeds through an (R)-styrene epoxide that is prepared via enantioselective reduction of an α-chloroketone intermediate. Ring opening of the epoxide with 1-(4- methoxyphenyl)-2-methylpropan-2-amine provides olodaterol.

Technology Process of Olodaterol

There total 4 articles about Olodaterol which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.27%

6-benzyloxy-8-{(R)-1-hydroxy-2-[2-(4-methoxyphenyl)-1,1-dimethylethylamino]ethyl}-4H-benzo[1,4]oxazin-3-one (869478-13-7) → (R)-6-hydroxy-8-{(1R)-1-hydroxy-2-{[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino}ethyl}-4H-1,4-benzoxazin-3-one (868049-49-4)

Guidance literature:

With palladium 10% on activated carbon; hydrogen; In methanol; at 50 ℃; under 2250.23 Torr;

Reference yield: 37.0%

Olodaterol hydrochloride (869477-96-3) → (R)-6-hydroxy-8-{(1R)-1-hydroxy-2-{[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino}ethyl}-4H-1,4-benzoxazin-3-one (868049-49-4)

Guidance literature:

With potassium carbonate; In water; ethyl acetate; Product distribution / selectivity;

Reference yield: 37.0%

→ (R)-6-hydroxy-8-{(1R)-1-hydroxy-2-{[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino}ethyl}-4H-1,4-benzoxazin-3-one (868049-49-4)

Guidance literature:

upstream raw materials:

6-benzyloxy-8-{(R)-1-hydroxy-2-[2-(4-methoxyphenyl)-1,1-dimethylethylamino]ethyl}-4H-benzo[1,4]oxazin-3-one

Olodaterol hydrochloride

6-benzyloxy-8-((R)-2-chloro-1-hydroxyethyl)-4H-benzo[1,4]-oxazin-3-one

Downstream raw materials:

Olodaterol hydrochloride

Refernces

• 1、 Bouyssou, Thierry,Hoenke, Christoph,Rudolf, Klaus,Lustenberger, Philipp,Pestel, Sabine,Sieger, Peter,Lotz, Ralf,Heine, Claudia,Büttner, Frank H.,Schnapp, Andreas,Konetzki, Ingo. "Discovery of olodaterol, a novel inhaled β2-adrenoceptor agonist with a 24 h bronchodilatory efficacy". body text. p. 1410 - 1414. Retrieved 2010/07/10.
• 2、 -. "NOVEL ENANTIOMERICALLY PURE BETA-AGONISTS, METHOD FOR THE PRODUCTION AND THE USE THEREOF IN THE FORM OF A DRUG". Page/Page column 22. . Retrieved 2008/06/13.