Duloxetine

Base Information

• Chemical Name: Duloxetine
• CAS No.: 116539-59-4
• Molecular Formula: C₁₈H₁₉NOS
• Molecular Weight: 297.421
• Hs Code.: 2934999090
• UNII: O5TNM5N07U
• DSSTox Substance ID: DTXSID6048385
• Nikkaji Number: J550.708A
• Wikipedia: Duloxetine
• Wikidata: Q411932
• NCI Thesaurus Code: C65495
• RXCUI: 72625
• Pharos Ligand ID: 1UF6FFVNYYNG
• Metabolomics Workbench ID: 42822
• ChEMBL ID: CHEMBL1175
• Mol file: 116539-59-4.mol

Synonyms:Cymbalta;duloxetine;Duloxetine Ethanedioate (1:1), (+-)-isomer - T353987;Duloxetine HCl;duloxetine hydrochloride;duloxetine, (+)-isomer;HCl, Duloxetine;Hydrochloride, Duloxetine;LY 227942;LY 248686;LY-227942;LY-248686;LY227942;LY248686;N-methyl-3-(1-naphthalenyloxy)-2-thiophenepropanamine;N-methyl-3-(1-naphthalenyloxy)-3-(2-thiophene)propanamide

Chemical Property of Duloxetine

Chemical Property:

• Vapor Pressure: 7.23E-09mmHg at 25°C
• Refractive Index: 1.627
• Boiling Point: 466.2 °C at 760 mmHg
• PKA: 10.02±0.10(Predicted)
• Flash Point: 235.7 °C
• PSA: 49.50000
• Density: 1.158 g/cm³
• LogP: 5.82380
• XLogP3: 4.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 6
• Exact Mass: 297.11873540
• Heavy Atom Count: 21
• Complexity: 312

Purity/Quality:

98% ^*data from raw suppliers

(S)-N-Methyl-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propan-1-amine 95+% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antidepressant Agents
• Canonical SMILES: CNCCC(C1=CC=CS1)OC2=CC=CC3=CC=CC=C32
• Isomeric SMILES: CNCC[C@@H](C1=CC=CS1)OC2=CC=CC3=CC=CC=C32
• Recent ClinicalTrials: Therapeutic Efficacy in Women With Stress Urinary Incontinence
• Recent EU Clinical Trials: Efficacy of patient education and duloxetine, alone and in combination, for patients with multiorgan bodily distress syndrome: a partial-factorial randomized controlled trial (the EDULOX-trial)
• Recent NIPH Clinical Trials: Efficacy of Duloxetine for Chronic postsurgical Pain after Total Hip Arthroplasty
• Uses: Antidepressant.
• Clinical Use: Duloxetine has been approved for the treatment of depression and diabetic peripheral neuropathic pain. It is another analogue in the line of fluoxetine-based products from Lilly, in which the phenyl and phenoxy groups of fluoxetine have been respectively replaced with the benzene isostere, thiophene, and a naphthyloxy group (previously described under fluoxetine). Duloxetine exhibits dual inhibition with high affinity for the SERTs and NETs, with a five times preferential inhibition of the SERT. Duloxetine appears to be a more potent in vitro blocker of SERTs and NETs than venlafaxine. In humans, duloxetine has a low affinity for the other neuroreceptors, suggesting low incidence of unwanted adverse effects.
• Drug interactions: Potentially hazardous interactions with other drugsAntibacterials: metabolism inhibited by ciprofloxacin - avoid.Anticoagulants: possibly increased risk of bleeding with dabigatran.Other CNS medication: enhanced effect.Antidepressants: avoid with MAOIs, moclobemide, St John’s wort, tryptophan, venlaflaxine, amitriptyline, clomipramine and SSRIs due to increased risk of serotonin syndrome; increased risk of side effects with tricyclic antidepressants; fluvoxamine decreases the clearance of duloxetine by 77% - avoid; possible increased risk of convulsions with vortioxetine.Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol.Dapoxetine: avoid concomitant use.Methylthioninium: risk of CNS toxicity - avoid if possible.

Technology Process of Duloxetine

There total 67 articles about Duloxetine 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: 98.4%

duloxetine ethyl carbamate (896446-94-9) → Duloxetine (116539-58-3,116539-59-4,116539-60-7,116817-13-1)

Guidance literature:

With potassium hydroxide; In ethanol; toluene; at 85 - 100 ℃; for 2h; Temperature;

Reference yield: 94.7%

(S)-3-(1-naphthyloxy)-3-(2-thienyl)propionaldehyde + methylamine (74-89-5) → Duloxetine (116539-58-3,116539-59-4,116539-60-7,116817-13-1)

Guidance literature:

(S)-3-(1-naphthyloxy)-3-(2-thienyl)propionaldehyde; methylamine; In ethanol; at 60 - 65 ℃; for 4h;

With 5%-palladium/activated carbon; hydrogen; In ethanol; at 20 - 30 ℃; for 4h; under 1500.15 - 3000.3 Torr; Reagent/catalyst; Temperature; Autoclave;

Reference yield: 92.0%

(S)-N-methyl-N-phenoxycarbonyl-3-(1-naphthyloxy)-3-(2-thienyl)-1-propylamine (947686-09-1) → Duloxetine (116539-58-3,116539-59-4,116539-60-7,116817-13-1)

Guidance literature:

With sodium hydroxide; water; In dimethyl sulfoxide; at 115 ℃; for 6h;

upstream raw materials:

(S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine oxalate

1-Fluoronaphthalene

(S)-3-methylamino-1-(2-thienyl)-1-propanol

S-3-iodo-1-(2-thienyl)-1-(1-naphthalenyloxy)propane

Downstream raw materials:

(+)-(S)-N-methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine maleate

duloxetine hydrochloride

duloxetine

N-methyl-(S)-duloxetine

Refernces

• 1、 Sasane, Sachin A.,Husain, Mofazzal,Bhise, Nandu B.,Singh, Girij P.,Joseph, Alex,Shenoy, Gautham G.. "An Improved Process for Synthesis of (S)-Duloxetine Hydrochloride Involving Enzymatic Asymmetric Carbonyl Reduction on a Novel Ketoamine". . p. 1 - 8. Retrieved 2020/11/02.
• 2、 -. "Preparation method for chiral gamma-sec-amino-alcohol". Paragraph 0286-0292. . Retrieved 2016/10/08.