Eletriptan

Base Information

• Chemical Name: Eletriptan
• CAS No.: 143322-58-1
• Molecular Formula: C22H26N2O2S
• Molecular Weight: 382.527
• European Community (EC) Number: 640-088-3
• UNII: 22QOO9B8KI
• DSSTox Substance ID: DTXSID9046861
• Nikkaji Number: J979.643F
• Wikipedia: Eletriptan
• Wikidata: Q415032
• NCI Thesaurus Code: C65509
• RXCUI: 231049
• Pharos Ligand ID: ZFH1VSJFLQCP
• Metabolomics Workbench ID: 42618
• ChEMBL ID: CHEMBL1510
• Mol file: 143322-58-1.mol

Synonyms:1H-Indole,3-[(1-methyl-2-pyrrolidinyl)methyl]-5-[2-(phenylsulfonyl)ethyl]-, (R)-;(R)-5-[2-(Benzenesulfonyl)ethyl]-3-[(N-methylpyrrolidin-2-yl)methyl]-1H-indole;UK 116044;Eletriptan hydrochloride;Eletriptan HBr;

Chemical Property of Eletriptan

Chemical Property:

• Appearance/Colour: yellow foam
• Vapor Pressure: 1.58E-16mmHg at 25°C
• Boiling Point: 613.4 °C at 760 mmHg
• PKA: 17.14±0.30(Predicted)
• Flash Point: 324.8 °C
• PSA: 61.55000
• Density: 1.235 g/cm³
• LogP: 4.83970
• Storage Temp.: Hygroscopic, Refrigerator, Under Inert Atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 4.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 6
• Exact Mass: 382.17149925
• Heavy Atom Count: 27
• Complexity: 582

Purity/Quality:

98% ^*data from raw suppliers

Eletriptan ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN1CCCC1CC2=CNC3=C2C=C(C=C3)CCS(=O)(=O)C4=CC=CC=C4
• Isomeric SMILES: CN1CCC[C@@H]1CC2=CNC3=C2C=C(C=C3)CCS(=O)(=O)C4=CC=CC=C4
• Recent ClinicalTrials: Efficacy, Safety, and Tolerability of Oral Eletriptan for Treatment of Acute Migraine
• Recent EU Clinical Trials: A randomised, double-blind, placebo- and active comparator-controlled, five parallel groups study to investigate the efficacy and safety of BI 44370 TA (50 mg, 200 mg, and 400 mg) administered orally once during an acute migraine attack of moderate or severe intensity
• Recent NIPH Clinical Trials: MATRIX(Migrainer Assess TRiptane eXamination)
• General Description: Eletriptan is a selective serotonin (5-HT1B/1D) receptor agonist used in the treatment of acute migraine attacks. It is synthesized via a Fischer indole cyclization approach, which has been optimized for improved yield, cost-efficiency, and environmental sustainability by employing L-ascorbic acid for reduction and classical resolution to obtain the active (R)-enantiomer. This second-generation process addresses previous limitations, such as high costs and waste generation, offering a more scalable and sustainable production method.

Technology Process of Eletriptan

There total 39 articles about Eletriptan 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: 99.83%

3-[[(R)-1-methyl-2-pyrrolidinyl]methyl]-5-[2-(phenyl-sulfonyl)ethyl]indole para-toluenesulfonate (1162655-06-2) → eletriptan (143322-58-1)

Guidance literature:

With ammonia; In tert-butyl methyl ether; water; at 20 - 25 ℃; pH=10 - 10.5;

Reference yield: 92.0%

(R)-5-[(2-phenylsulfonyl)ethenyl]-3-(N-methylpyrrolidine-2-ylmethyl)-1H-indole (180637-89-2) → eletriptan (143322-58-1)

Guidance literature:

With methanesulfonic acid; 5%-palladium/activated carbon; hydrogen; In water; acetone; at 25 - 35 ℃; for 0.0833333h; under 3800.26 - 4560.31 Torr;

DOI:10.1021/op3002454

Reference yield: 91.54%

(R)-5-[(2-phenylsulfonyl)ethenyl]-3-(N-methylpyrrolidine-2-ylmethyl)-1H-indole (180637-89-2) → 5-ethyl-3-{[1-methylpyrrolidin-2-yl]methyl}-1H-indole (209682-64-4) + eletriptan (143322-58-1)

Guidance literature:

With methanesulfonic acid; 5%-palladium/activated carbon; hydrogen; In water; acetone; at 25 - 30 ℃;

DOI:10.1021/op3002454

upstream raw materials:

(R)-5-[(2-phenylsulfonyl)ethenyl]-3-(N-methylpyrrolidine-2-ylmethyl)-1H-indole

methanesulfonic acid

(2R)-2-[2-(1,3-dioxan-2yl)ethyl]-1-methylpyrrolidine (2R,3R)-2,3-bis(benzyloxy)succinic acid

3-[[(R)-1-methyl-2-pyrrolidinyl]methyl]-5-[2-(phenyl-sulfonyl)ethyl]indole para-toluenesulfonate

Downstream raw materials:

eletriptan hydrobromide

3-(N-methyl-2(R)-pyrrolidinylmethyl)-5-(2-phenylsulphonylethyl)-1H-indole hydrobromide monohydrate

(1S,2R)-3-[(1-methyl-2-pyrrolidinyl)methyl]-5-[2-(phenylsulfonyl)ethyl]-N-oxide-1H-indole

(1R,2R)-3-[(1-methyl-2-pyrrolidinyl)methyl]-5-[2-(phenylsulfonyl)ethyl]-N-oxide-1H-indole

Refernces

Second-generation process research towards eletriptan: A fischer indole approach

10.1021/op100251q

The study presents the development of a second-generation synthetic process for eletriptan, a drug used to treat migraines, employing a Fischer indole cyclization approach. The new process aims to overcome the limitations of the existing manufacturing route, which includes the use of expensive and harmful starting materials, and generates significant waste. The research details the synthesis of key intermediates, such as aldehyde 8 and hydrazine 10, and explores various methods to improve yield and scalability. The study also discusses the successful application of the Fischer indole reaction to synthesize eletriptan and the optimization of the process using L-ascorbic acid for the reduction of diazonium salts to aryl hydrazines, resulting in a more cost-effective, efficient, and environmentally friendly synthesis route. The final objective was achieved by synthesizing the single enantiomer of eletriptan (R)-7 through classical resolution techniques, offering a potentially more sustainable and scalable method for its production.