Milnacipran

Base Information

• Chemical Name: Milnacipran
• CAS No.: 92623-85-3
• Deprecated CAS: 105310-09-6
• Molecular Formula: C₁₅H₂₂N₂O
• Molecular Weight: 246.352
• UNII: ES1O38J3C4,G56VK1HF36
• DSSTox Substance ID: DTXSID3048287,DTXSID601025164
• Nikkaji Number: J259.861B
• Wikipedia: Milnacipran
• Wikidata: Q421058
• NCI Thesaurus Code: C78021
• RXCUI: 588250
• Pharos Ligand ID: V5WCGN16MG95,V5WCYMYYF8T6
• Metabolomics Workbench ID: 43642
• ChEMBL ID: CHEMBL252923
• Mol file: 92623-85-3.mol

Synonyms:1 Phenyl 1 diethylaminocarbonyl 2 aminomethylcyclopropane HCl;1-phenyl-1-diethylaminocarbonyl-2-aminomethylcyclopropane HCl;F 2207;F-2207;F2207;Ixel;midalcipran;milnacipran;milnacipran hydrochloride;Savella

Chemical Property of Milnacipran

Chemical Property:

• Vapor Pressure: 2.19E-06mmHg at 25°C
• Melting Point: 228-228.5oC
• Refractive Index: 1.553
• Boiling Point: 393 °C at 760 mmHg
• PKA: 10.36±0.29(Predicted)
• Flash Point: 191.5 °C
• PSA: 46.33000
• Density: 1.077 g/cm³
• LogP: 2.47170
• Storage Temp.: 2-8°C
• Solubility.: H2O: 19 mg/mL
• XLogP3: 1.4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 5
• Exact Mass: 246.173213330
• Heavy Atom Count: 18
• Complexity: 295

Purity/Quality:

98%,99%, ^*data from raw suppliers

Milnacipran ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCN(CC)C(=O)C1(CC1CN)C2=CC=CC=C2
• Isomeric SMILES: CCN(CC)C(=O)[C@@]1(C[C@@H]1CN)C2=CC=CC=C2
• Recent ClinicalTrials: Evaluation of the Initial Prescription of Ketamine and Milnacipran in Depression in Patients With a Progressive Disease
• Recent EU Clinical Trials: A study to investigate the analgesic effects of buprenorphine and milnacipram in healthy volunteers.
• Recent NIPH Clinical Trials: A randomised controlled trial of treatment with SSRI or SNRI for patients with functional (psychogenic) dizziness
• Description: Ixel was launched in France as an antidepressant. There are several synthetic routes, the shortest of which is five steps using benzyl cyanide as the starting material. It is a specific serotonin and noradrenaline reuptake inhibitor (SNRI). This dual mechanism of action makes it superior to selective serotonin reuptake inhibitors (SSRI) like fluoxetine and fluvoxamine. Ixel has no significant effect on postsynaptic receptors, very limited effect on cardiac function, and no quinidine-like arrhythmal effects. It has a good side effect profile with lower incidence of anticholinergic-like side effects, less sedation due to histamine H1-receptor binding, and a lack of α1- adrenoceptor antagonism. Ixel has a short half-life (7 hr) with no active metabolites. It is not metabolized by CYP450 therefore drug interaction is unlikely. It is superior in the treatment of serious depression with no need to titrate drug dose.
• Clinical Use: (±)-Milnacipran is the ci s-aminomethyl derivative of phenylcyclopropanecarboxamide that acts by inhibiting both NE and 5-HT reuptake. It is structurally different from the other NSRIs and currently is only available in Europe as a racemic mixture, with both enantiomers exhibiting antidepressant activity. Substituting the aminomethyl group of milnacipran with an aminopropyl gives a milnacipran homologue that exhibits antidepressant activity as a potent N-methyl-D-aspartate (NMDA) receptor antagonist. A glutamate hypothesis is being investigated as an alternative mechanism of depression.

Technology Process of Milnacipran

There total 80 articles about Milnacipran 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: 100.0%

C13H17NO4*C15H22N2O → (2S)-2-[(tert-butoxycarbonyl)amino]-2-phenylethanoic acid (2900-27-8) + (1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide (96847-54-0,92623-85-3,96847-55-1)

Guidance literature:

With sodium hydroxide; In water; at 20 ℃; pH=11;

Reference yield: 100.0%

cis-(±)-1-phenyl-2-(aminomethyl)-N,N-diethylcyclopropanecarboxamide hydrochloride (86181-08-0,101152-94-7,175131-61-0) → milnacipran (105310-09-6,96847-54-0,92623-85-3,96847-55-1)

Guidance literature:

With sodium hydroxide; In water;

Reference yield: 100.0%

C19H28N2O2 → (1R,2S)-milnacipran (96847-54-0,92623-85-3,96847-55-1)

Guidance literature:

With hydrogenchloride; In water; for 3h; Reflux;

DOI:10.1016/j.molcatb.2014.03.015

upstream raw materials:

(1R,2R)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-1-phenyl-cyclopropanecarboxylic acid diethylamide

(1R,2R)-2-Hydroxymethyl-1-phenyl-cyclopropanecarboxylic acid diethylamide

Toluene-4-sulfonic acid (1R,2R)-2-diethylcarbamoyl-2-phenyl-cyclopropylmethyl ester

(1SR,2RS)-2-((1,3-dioxoisoindolin-2-yl)methyl)-N,N-diethyl-1-phenylcyclopropane carboxamide

Downstream raw materials:

N,N-diethyl-2-methyl-1-phenylcycloprop-2-enecarboxamide

2-(aminomethyl)-1-phenylcyclopropanecarboxamide

Refernces

• 1、 Sanfilippo, Claudia,Nicolosi, Giovanni,Patti, Angela. "Milnacipran as a challenging example of aminomethyl substrate for lipase-catalyzed kinetic resolution". . p. 82 - 86. Retrieved 2014.
• 2、 -. "Preparation of leveminacipran hydrochloride". . . Retrieved 2020/06/16.
• 3、 -. "Preparation method of levomilnacipran hydrochloride". . . Retrieved 2017/04/19.