5560-59-8

Basic information

• Product Name: Alverine citrate
• Synonyms: n-ethyl-3,3'-diphenyldipropylamine citrate;N-ETHYL-3,3'-DIPHENYLDIPROPYLAMINE CITRATE SALT;N-ETHYL-3,3-DIPHENYLDIPROPYLAMINE CITRATE SALT;Alverine base or citrate;alverine dihydrogen citrate;Profenil citrate;AntispasMin;CalMabel
• CAS NO: 5560-59-8
• Molecular Formula: C₆H₈O₇*C₂₀H₂₇N
• Molecular Weight: 473.56
• EINECS: 226-929-3
• Product Categories: Amines;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;SPASMAVERINE;Pharmaceutical intermediates
• Mol File: 5560-59-8.mol
• Article Data: 3

Chemical Properties

• Melting Point: 100-102°
• Boiling Point: 358.8 °C at 760 mmHg
• Flash Point: 174.4 °C
• Appearance: COA
• Vapor Pressure: 2.48E-05mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: Slightly soluble in water and in methylene chloride, sparingly soluble in ethanol (96 per cent).
• CAS DataBase Reference: Alverine citrate(CAS DataBase Reference)
• NIST Chemistry Reference: Alverine citrate(5560-59-8)
• EPA Substance Registry System: Alverine citrate(5560-59-8)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 5560-59-8(Hazardous Substances Data)

Usage

Chemical Properties

White or almost white, crystalline powder.

Uses

Different sources of media describe the Uses of 5560-59-8 differently. You can refer to the following data:
1. Used for studies of pharmacological activity including:Synergism with fluconazole against Saccharomyces cerevisiae and Candida albicansEfficacy of combination with simeticone on abdominal pain associated with irritable bowel syndromeNutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysisDrug effects viewed from a signal transduction network perspectiveEnhanced cytotoxic effect of proteasome inhibitor MG132Mechanism of action on phasic smooth muscles
2. An adrenergic-β3 receptor agonist. Antispasmodic.
3. anticholinergic

Definition

ChEBI: The citrate salt of alverine, resulting from the reaction of equimolar amounts of alvarine and citric acid. An antispasmodic that acts directly on intestinal and uterine smooth muscle, it is used in the treatment of irritable bowel syndrome.

Therapeutic Function

Anticholinergic, Spasmolytic

InChI:InChI=1/C20H27N.C6H8O7/c1-2-21(17-9-15-19-11-5-3-6-12-19)18-10-16-20-13-7-4-8-14-20;7-3(8)1-6(13,5(11)12)2-4(9)10/h3-8,11-14H,2,9-10,15-18H2,1H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)

Synthetic route

alverine (150-59-4) + citric acid (77-92-9) → alverine citrate (5560-59-8)

Conditions	Yield
In ethyl acetate; isopropyl alcohol at 45 - 50℃; Solvent; Temperature;	92%
In ethanol at 20℃;	66.9%

1-Bromo-3-phenylpropane (637-59-2) → alverine citrate (5560-59-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrabutylammomium bromide; sodium hydroxide / 85 - 90 °C 2: ethanol / 20 °C View Scheme

3-Phenyl-1-propanol (122-97-4) → alverine citrate (5560-59-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 0 - 30 °C 2: sodium bromide / N,N-dimethyl-formamide / 25 - 30 °C 3: N-benzyl-N,N,N-triethylammonium chloride; triethylamine / N,N-dimethyl-formamide; water / 10 - 40 °C 4: ethyl acetate; isopropyl alcohol / 45 - 50 °C View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid; sodium bromide / water / 20 °C / Reflux 2.1: tetrabutylammomium bromide; sodium hydroxide / 85 - 90 °C 2.2: 6 h / 15 °C View Scheme

3-phenylpropanol methanesulfonate (69804-99-5) → alverine citrate (5560-59-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium bromide / N,N-dimethyl-formamide / 25 - 30 °C 2: N-benzyl-N,N,N-triethylammonium chloride; triethylamine / N,N-dimethyl-formamide; water / 10 - 40 °C 3: ethyl acetate; isopropyl alcohol / 45 - 50 °C View Scheme

1-Bromo-3-phenylpropane (637-59-2) + ethanamine hydrochloride (557-66-4) + citric acid (77-92-9) → alverine citrate (5560-59-8)

Conditions	Yield
Stage #1: 1-Bromo-3-phenylpropane; ethanamine hydrochloride With tetrabutylammomium bromide; sodium hydroxide at 85 - 90℃; Stage #2: citric acid In ethanol at 15℃; for 6h; Temperature;	10.48 g

Upstream product

• 637-59-2 1-Bromo-3-phenylpropane 
• 557-66-4 ethanamine hydrochloride 
• 77-92-9 citric acid 
• 69804-99-5 3-phenylpropanol methanesulfonate 
• 122-97-4 3-Phenyl-1-propanol 
• 150-59-4 alverine 

Relevant articles and documents

Method for reducing residues of N-ethyl-3-phenylpropylamine in alverine

The invention relates to a method for reducing residues of N-ethyl-3-phenylpropylamine in alverine, and belongs to an impurity removal method of compounds. The method comprises the following steps: dissolving an intermediate alverine crude product containing impurity N-ethyl-3-phenylpropylamine into a water-insoluble organic solvent, extracting an organic layer by using an aqueous solution with appropriate pH and discarding a water layer; drying and filtering the organic layer, decompressing and evaporating the solvent to dryness. According to the method disclosed by the invention, a clear, simple and reliable solution to the residues of the N-ethyl-3-phenylpropylamine in the intermediate alverine is provided for the first time, so that the subsequently produced crude drug citric acid alverine has higher quality and the residue amount does not exceed 0.15 percent. The method has the advantages of simplicity, feasibility, low cost, few wastes and suitability for industrial popularization.

A new method for the preparation of alverine citrate

The invention discloses a novel preparation method of alverine citrate, which comprises the following steps: reacting 3-phenylhalopropane and ethylamine hydrochloride used as initial raw materials in an alkaline system to generate diphenylpropyl ethylamine, and refining under the interaction between the organic layer and the citric acid to obtain the alverine citrate. The process route has the characteristics of accessible raw materials, fewer reaction steps, mild conditions, high yield and the like and is simple to operate, and thus, is an environment-friendly synthesis route which can easily implement industrialization.