Production Method 1

89365-50-4

86-48-6

89365-50-4

86-48-6

Reaction Conditions

1.1 Solvents: Methyl ethyl ketone ;  rt

Reference

Process for the preparation of salmeterol xinafoate from 2-(bromoethyl)benzene

, China, , ,

Production Method 2

89365-50-4

86-48-6

89365-50-4

86-48-6

Reaction Conditions

1.1 Solvents: Acetone ;  40 min, 30 °C

Reference

Preparation method of salmeterol xinafoate

, China, , ,

Production Method 3

934842-69-0

86-48-6

89365-50-4

86-48-6

Reaction Conditions

1.1 Solvents: Ethanol ;  rt

Reference

A new route for synthesis of salmeterol xinafoate

Wu, Xiaochun, Xinan Shifan Daxue Xuebao, 2009, 34(4), 85-88

Production Method 4

262857-01-2

86-48-6

89365-50-4

86-48-6

Reaction Conditions

1.1 Reagents: Acetic acid Solvents: Water ;  3 h, 70 °C
1.2 Solvents: Ethyl acetate ;  16 h, rt

Reference

Preparation of deuterium substituted ethanolamines as adrenergic modulators for disease treatment

, United States, , ,

Production Method 5

89365-50-4

86-48-6

Reaction Conditions

Reference

Utility of Von Pechman synthesis of coumarin reaction for development of spectrofluorimetric method for quantitation of salmeterol xinafoate in pharmaceutical preparations and human plasma

Awad, Mohamed; Hammad, Mohamed A. ; Abdel-Megied, Ahmed M. ; Omar, Mahmoud A., Luminescence, 2018, 33(5), 913-918

Production Method 6

89365-50-4

86-48-6

Reaction Conditions

Reference

An improved process for the preparation of salmeterol xinafoate

, India, , ,

Production Method 7

2691147-83-6

89365-50-4

Reaction Conditions

1.1 Reagents: Lithium aluminum hydride Solvents: Diethyl ether ;  rt; 1 h, rt
1.2 Reagents: Water

Reference

Structural isomers of saligenin-based β2-agonists: synthesis and insight into the reaction mechanism

Knezevic, Anamarija; Novak, Jurica; Bosak, Anita; Vinkovic, Marijana, Organic & Biomolecular Chemistry, 2020, 18(47), 9675-9688

Production Method 8

934842-69-0

89365-50-4

Reaction Conditions

1.1 Reagents: Formic acid Catalysts: Palladium Solvents: Methanol ;  overnight, 35 °C

Reference

A new route for synthesis of salmeterol xinafoate

Wu, Xiaochun, Xinan Shifan Daxue Xuebao, 2009, 34(4), 85-88

Production Method 9

727641-92-1

94749-73-2

89365-50-4

Reaction Conditions

1.1 Reagents: Triethylamine Catalysts: Potassium iodide Solvents: Dimethylformamide ;  12 h, 80 °C

Reference

Study on the process for synthesis of salmeterol

Shen, Li-qun, Guangzhou Huagong, 2008, 36(4), 46-47

Production Method 10

97664-54-5

915132-89-7

89365-50-4

Reaction Conditions

1.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Methanol ;  overnight, 2.06 MPa, rt
1.2 Reagents: Acetic acid Solvents: Methanol ;  48 h, 40 °C
1.3 Reagents: Sodium bicarbonate Solvents: Water

Reference

New synthetic route to salmeterol

Zhou, Di; Liu, Juntao; Lu, Yixiang; Jia, Xian; Li, Xingshu, Zhongguo Yaowu Huaxue Zazhi, 2009, 19(2), 123-125

Production Method 11

97664-58-9

1239368-65-0

89365-50-4

Reaction Conditions

1.1 Solvents: Ethanol ;  12 h, reflux; reflux → rt
1.2 Reagents: Sodium borohydride ;  24 h, rt

Reference

The synthesis of salmeterol

Ying, Min; Zhang, Huaxing, Guangdong Huagong, 2009, 36(12),

Production Method 12

89365-50-4

86-48-6

89365-50-4

86-48-6

Reaction Conditions

1.1 Solvents: Acetone ;  3 - 4 h, 25 - 35 °C

Reference

Preparation of salmeterol and salts thereof

, India, , ,

Production Method 13

89365-50-4

86-48-6

89365-50-4

86-48-6

Reaction Conditions

1.1 Solvents: Acetone ;  30 min, 45 °C; 45 °C → 25 °C; 1 h, 25 °C
1.2 Solvents: tert-Butyl methyl ether ;  25 °C → 10 °C; 2 h, 10 °C

Reference

Process for preparation of salmeterol

, World Intellectual Property Organization, , ,

Production Method 14

89365-50-4

86-48-6

89365-50-4

86-48-6

Reaction Conditions

1.1 Solvents: Methanol ;  1 h, 30 °C; 30 °C → 22 °C; 2 h, 18 - 22 °C

Reference

Improved process for the preparation of salmeterol xinafoate

, India, , ,

Production Method 15

89365-50-4

86-48-6

89365-50-4

86-48-6

Reaction Conditions

1.1 Solvents: Methanol ;  25 - 30 °C; 3 h, 0 °C

Reference

A method for preparing salmeterol hydroxynaphthoate

, China, , ,

Production Method 16

89365-50-4

86-48-6

89365-50-4

86-48-6

Reaction Conditions

1.1 Solvents: Methanol ,  Ethyl acetate

Reference

Preparation of salmeterol xinafolate

Anonymous, Research Disclosure, 2006, 506,

Production Method 17

89365-50-4

86-48-6

89365-50-4

86-48-6

Reaction Conditions

1.1 Solvents: Isopropanol ;  rt → 70 °C; 8 h, 70 °C

Reference

Synthesis route of salmeterol xinafoate

Jiang, Zhi-gan; Hua, Zheng-mao; Mai, Lu-gen; Yang, Li-ge, Huadong Shifan Daxue Xuebao, 2003, (3), 102-104

Production Method 18

89365-50-4

86-48-6

Reaction Conditions

Reference

Preparation of salmeterol and its application

, China, , ,

Production Method 19

89365-50-4

86-48-6

Reaction Conditions

Reference

Improved process for the preparation A Long-acting β2-adrenergic agonist (LABA) Salmeterol and identification, characterization and control of its potential process impurity

Reddy, Sahadeva; Rajan, S. T.; Parusuramudu; Reddy, Raghupathi; Chakravarthy, I. E., Pharma Chemica, 2016, 8(8), 28-35

Production Method 20

89365-50-4

86-48-6

Reaction Conditions

Reference

Process for the preparation of crystalline salmeterol and its xinafoate salt

, World Intellectual Property Organization, , ,

Production Method 21

89365-50-4

86-48-6

Reaction Conditions

Reference

Process for preparation of salmeterol

, India, , ,

Production Method 22

89365-50-4

86-48-6

Reaction Conditions

Reference

Process for preparation of salmeterol xinafoate

, World Intellectual Property Organization, , ,

Production Method 23

89365-50-4

86-48-6

Reaction Conditions

Reference

Medicaments containing betamimetic drugs and a novel anticholinesterase drug for treating respiratory tract diseases

, World Intellectual Property Organization, , ,

Production Method 24

89365-50-4

86-48-6

Reaction Conditions

Reference

Phenethanolamine derivatives useful in the treatment of respiratory problems

, Federal Republic of Germany, , ,

Production Method 25

934842-69-0

89365-50-4

Reaction Conditions

1.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Ethanol ;  36 h, 58 psi, 45 °C

Reference

An Efficient and Practical Synthesis of Salmeterol

Lu, Yongping; Xu, Xinliang; Zhang, Xingxian, Organic Preparations and Procedures International, 2015, 47(2), 168-172

Production Method 26

27475-14-5

97664-55-6

89365-50-4

Reaction Conditions

1.1 Reagents: Sodium carbonate Solvents: Dichloromethane ,  Water ;  10 min, pH 8 - 9, 25 - 35 °C
1.2 Reagents: Diisopropylethylamine ;  25 - 35 °C; 4 h, 25 - 35 °C
1.3 Reagents: Vitride Solvents: Toluene ;  35 °C → 5 °C; 1 h, 0 - 5 °C
1.4 Reagents: Monopotassium monosodium tartrate tetrahydrate Solvents: Water ;  0 - 5 °C; 1 h, 25 - 35 °C
1.5 Reagents: Hydrogen Catalysts: Palladium Solvents: Methanol ;  2 h, 25 - 35 °C

Reference

Improved process for the preparation A Long-acting β2-adrenergic agonist (LABA) Salmeterol and identification, characterization and control of its potential process impurity

Reddy, Sahadeva; Rajan, S. T.; Parusuramudu; Reddy, Raghupathi; Chakravarthy, I. E., Pharma Chemica, 2016, 8(8), 28-35

Production Method 27

163923-19-1

89365-50-4

Reaction Conditions

1.1 Reagents: Sodium borohydride Solvents: Methanol
1.2 Reagents: Hydrochloric acid Solvents: Water
1.3 Reagents: Sodium carbonate Solvents: Water
1.4 Reagents: Hydrogen Catalysts: Palladium Solvents: Methanol

Reference

A new synthetic approach to salmeterol

Rong, Yajing; Ruoho, Amold E., Synthetic Communications, 1999, 29(12), 2155-2162

Salmeterol Raw materials

• Hexanal, 6-(4-phenylbutoxy)-
• 5-(2-Amino-1-hydroxyethyl)-salicylsaeure-methylester
• 6-(4-Phenylbutoxy)-1-hexanamine
• Salmeterol
• 2-Hydroxy-5-6-(4-phenylbutoxy)hexyl(phenylmethyl)aminoacetyl-benzaldehyde
• 1,3-Benzenedimethanol,4-hydroxy-a1-6-(4-phenylbutoxy)hexyl(phenylmethyl)aminomethyl-
• Benzene,[4-[(6-bromohexyl)oxy]butyl]-
• 4H-1,3-Benzodioxin-6-methanol, 2,2-dimethyl-alpha-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-
• 2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)acetaldehyde
• 2-Benzyloxy-5-bromoacetylbenzoic Acid Methyl Ester
• 6-(4-Phenylbutoxy)hexylbenzylamine
• 1-hydroxynaphthalene-2-carboxylic acid
• 4H-1,3-Benzodioxin-6-methanol, α-(aminomethyl)-2,2-dimethyl-
• Methyl 2-hydroxy-5-[1-hydroxy-2-[[6-(4-phenylbutoxy)hexyl]amino]ethyl]benzoate

Salmeterol Preparation Products

• Salmeterol (89365-50-4)
• 1-hydroxynaphthalene-2-carboxylic acid (86-48-6)

• 1. Excimer and exciplex formation in a pair of bright phosphorescent isomers constructed from Cu3(pyrazolate)3 and Cu3I3 coordination luminophores?
  Shun-Ze Zhan,Mian Li,Xiao-Ping Zhou,Dan Li,Seik Weng Ng RSC Adv., 2011,1, 1457-1459
• 2. Evidence of rutile-to-anatase photo-induced electron transfer in mixed-phase TiO2 by solid-state NMR spectroscopy?
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  Min Kim,Jae-Joon Lee,Tengling Ye,Panagiotis E. Keivanidis,Kilwon Cho J. Mater. Chem. C, 2020,8, 1686-1696
• 5. Fast synthesis of red Li3BaSrLn3(WO4)8:Eu3+ phosphors for white LEDs under near-UV excitation by a microwave-assisted solid state reaction method and photoluminescence studies
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• Solvents and Organic Chemicals Organic Compounds Benzenoids Benzene and substituted derivatives Benzyl alcohols

Introduction to Salmeterol (CAS No. 89365-50-4) in Modern Pharmaceutical Research

Salmeterol, a long-acting β?-adrenergic receptor agonist, is widely recognized for its significant role in the management of respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). With the chemical formula C₃₂H₃₉N₂O₂ and a CAS number of 89365-50-4, this compound has garnered substantial attention in both clinical and academic settings. The pharmacological properties of salmeterol make it an essential component in therapeutic strategies aimed at improving lung function and reducing exacerbations in patients with chronic respiratory disorders.

The mechanism of action of salmeterol involves the activation of β?-adrenergic receptors, which leads to the relaxation of bronchial smooth muscles. This results in increased airflow and alleviation of symptoms associated with airway obstruction. The prolonged duration of action, typically lasting for at least 12 hours, makes salmeterol a preferred choice for patients requiring regular maintenance therapy. This pharmacokinetic profile is attributed to its high affinity for β?-adrenergic receptors and its ability to resist rapid metabolism.

In recent years, research has delved deeper into the molecular mechanisms underlying the therapeutic effects of salmeterol. Studies have highlighted its potential not only as a bronchodilator but also as an anti-inflammatory agent. The compound has been observed to modulate various inflammatory pathways, including the reduction of cytokine release and the inhibition of neutrophil recruitment. These findings suggest that salmeterol may offer additional benefits beyond its primary role in bronchodilation, potentially contributing to a more comprehensive management of respiratory diseases.

The development of novel drug delivery systems has further enhanced the efficacy and patient compliance associated with salmeterol. Formulations such as dry powder inhalers (DPIs) have been engineered to deliver precise doses of the compound directly to the lungs, minimizing systemic absorption and side effects. This targeted delivery approach has been particularly beneficial for patients with severe respiratory conditions who require consistent and reliable therapeutic intervention.

Recent clinical trials have demonstrated the long-term safety and efficacy of salmeterol when used as part of combination therapy regimens. These trials have shown that when paired with corticosteroids, salmeterol can significantly reduce the frequency of exacerbations and improve quality of life for patients with COPD. The synergistic effects observed in these combination therapies underscore the importance of multifaceted approaches in managing chronic respiratory diseases.

The growing body of evidence supporting the use of salmeterol has also prompted exploration into its potential applications beyond traditional respiratory treatments. Preliminary research has investigated its role in conditions such as cardiovascular disease and metabolic disorders, where β?-adrenergic receptor activation may contribute to improved outcomes. While these applications are still under investigation, they highlight the broad therapeutic potential of salmeterol and its derivatives.

Advances in computational chemistry and molecular modeling have furthered our understanding of how salmeterol interacts with biological targets. These tools have enabled researchers to predict and optimize the structure-activity relationships (SAR) of salmeterol analogs, leading to the discovery of new compounds with enhanced pharmacological profiles. Such innovations are crucial for addressing emerging challenges in drug development and ensuring that patients continue to benefit from cutting-edge therapies.

The regulatory landscape for salmeterol has evolved alongside advancements in pharmaceutical technology and our understanding of its mechanisms of action. Regulatory agencies now require comprehensive data demonstrating both efficacy and safety across diverse patient populations. This stringent evaluation process ensures that salmeterol remains a trusted and effective treatment option for patients worldwide.

Looking ahead, the future prospects for salmeterol are promising, with ongoing research aimed at expanding its therapeutic applications and improving its delivery systems. Collaborative efforts between academia, industry, and regulatory bodies will be essential in translating these findings into tangible benefits for patients. As our understanding of respiratory diseases continues to grow, compounds like salmeterol will remain at the forefront of therapeutic innovation.

• 321-97-1((-)-Pseudoephedrine)
• 329-65-7(DL-Epinephrine)
• 94749-11-8(4-Hydroxy-α1-6-(3-phenylpropoxy)hexylaminomethyl-1,3-benzenedimethanol)
• 1391054-40-2(3-De(hydroxymethyl)-3-methyl Salmeterol)
• 135293-13-9(2''-O-Rhamnosylicariside II)
• 86-48-6(1-hydroxynaphthalene-2-carboxylic acid)
• 108928-81-0(4-Hydroxy-a1-6-(1-methyl-3-phenylpropoxy)hexylaminomethyl-1,3-benzenedimethanol (Salmeterol Impurity))
• 1391052-04-2(4-O-2-Hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl Salmeterol)
• 94749-02-7(4-Hydroxy-a1-6-(2-phenylethoxy)hexylaminomethyl-1,3-benzenedimethanol)
• 1391051-88-9(Salmeterol Dimer Impurity (Mixture of Diastereomers))