53885-35-1

Basic information

• Product Name: Ticlopidine hydrochloride
• Synonyms: 4-c-32;53-32c;panaldine;ticlid;ticlodix;ticlodone;5-(o-chlorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridinium chloride;ticlodipine hydrochloride
• CAS NO: 53885-35-1
• Molecular Formula: C₁₄H₁₄ClNS*ClH
• Molecular Weight: 300.25
• EINECS: 258-837-4
• Product Categories: Active Pharmaceutical Ingredients;Heterocyclic Compounds;Bases & Related Reagents;Heterocycles;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals;Sulfur & Selenium Compounds;API's;Purinergics P2 receptor;THONZIDE;API
• Mol File: 53885-35-1.mol
• Article Data: 14

Chemical Properties

• Melting Point: 205°C
• Boiling Point: 367.3 °C at 760 mmHg
• Flash Point: 175.9 °C
• Appearance: White powder
• Density: 1.37 g/cm3
• Vapor Pressure: 1.38E-05mmHg at 25°C
• Storage Temp.: Desiccate at RT
• Solubility: Sparingly soluble in water and in anhydrous ethanol, very slightly soluble in ethyl acetate.
• PKA: 7.64(at 25℃)
• Water Solubility: Soluble to 100 mM in water and to 100 mM in DMSO.
• Merck: 14,9421
• CAS DataBase Reference: Ticlopidine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Ticlopidine hydrochloride(53885-35-1)
• EPA Substance Registry System: Ticlopidine hydrochloride(53885-35-1)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38
• Safety Statements: 36-37/39-26
• WGK Germany: 3
• RTECS: XJ9089100
• Hazardous Substances Data: 53885-35-1(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Originator

Ticlid,Millot,France,1978

Uses

Different sources of media describe the Uses of 53885-35-1 differently. You can refer to the following data:
1. Ticlopidine hydrochloride is a selective P2Y12 receptor antagonist. It inhibits ADP-induced platelet aggregation and displays antithrombotic activity following oral administration in vivo.
2. An antithrombotic. a platelet aggregation inhibitor
3. mucolytic, antibacterial, surface active agent

Manufacturing Process

A solution of thieno[3,2-c]pyridine (13.5 g; 0.1 mol) and 2-chlorobenzyl chloride (17.7 g) in acetonitrile (150 ml) is boiled during 4 hours. After evaporation of the solvent, the solid residue consists of 5-(2- chlorobenzyl)-thieno[3,2-c]pyridinium chloride which melts at 166°C (derivative n° 30). This compound is taken up into a solution comprising ethanol (300 ml) and water (100 ml). Sodium borohydride (NaBH4)(20 g) is added portionwise to the solution maintained at room temperature. The reaction medium is maintained under constant stirring during 12 hours and is then evaporated. The residue is taken up into water and made acidic with concentrated hydrochloric acid to destroy the excess reducing agent. The mixture is then made alkaline with ammonia and extracted with ether. The ether solution is washed with water, dried and evaporated. The oily residue is dissolved in isopropanol (50 ml) and hydrochloric acid in ethanol solution is then added thereto. After filtration and recrystallization from ethanol, there are obtained 5-(2- chlorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride crystals (yield: 60%) having a melting point (Koefler block) of 190°C.

Therapeutic Function

Platelet aggregation inhibitor

Biological Activity

Selective P2Y 12 receptor antagonist. Inhibits ADP-induced platelet aggregation and displays antithrombotic activity following oral administration in vivo .

InChI:InChI=1/C14H14ClNS.ClH/c15-13-4-2-1-3-11(13)9-16-7-5-14-12(10-16)6-8-17-14;/h1-4,6,8H,5,7,9-10H2;1H

Synthetic route

N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine hydrochloride (60612-23-9) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
In 1,3-DIOXOLANE; ethyl acetate	95%
With hydrogenchloride In 1,3-dioxane; water at 90℃; for 6h; Temperature;	82%

1,3-DIOXOLANE (646-06-0) + N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine hydrochloride (60612-23-9) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
With hydrogenchloride	89%
With hydrogenchloride In water at 90℃; for 6h; Temperature;	82%
With hydrogenchloride In water at 90℃; for 6h; Temperature;	91 g

4,5,6,7-tetrahydrothieno[3,2-c]pyridine (54903-50-3) + 1-chloro-2-(chloromethyl)benzene (611-19-8) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
Stage #1: 4,5,6,7-tetrahydrothieno[3,2-c]pyridine; 1-chloro-2-(chloromethyl)benzene In dichloromethane at 60℃; for 1h; Stage #2: With hydrogenchloride In dichloromethane Reagent/catalyst; Solvent; Temperature;	87%

[2-(2-thyenyl)ethyl]amine (30433-91-1) + aqueous potassium carbonate + methyleneamine (2053-29-4) + 1-chloro-2-(chloromethyl)benzene (611-19-8) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
With hydrogenchloride; formaldehyd; potassium carbonate In tetrahydrofuran; methanol; water; toluene	84%

4,5,6,7-tetrahydrothieno[3,2-c]pyridine (54903-50-3) + di-isopropyl ether (108-20-3) + 1-chloro-2-(chloromethyl)benzene (611-19-8) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
With hydrogenchloride; sodium hydrogencarbonate In ethanol	83%

C13H14ClNS*(x)ClH → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
With hydrogenchloride In 1,3-dioxane; water at 90℃; for 6h; Temperature;	82%

pyrographite (7440-44-0) + N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine hydrochloride (60612-23-9) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
Stage #1: N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine hydrochloride With hydrogenchloride In 1,3-dioxane; water at 7 - 90℃; for 9h; Stage #2: pyrographite In ethanol at 4℃; for 4h; Temperature;	82%

Chloromethyl pivalate (18997-19-8) + N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine (69061-17-2) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
In dimethyl sulfoxide	51%

1,3 dithiane (505-23-7) + N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine hydrochloride (60612-23-9) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
In 1,2-dimethoxyethane	9.4 g (62.7%)

N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine (69061-17-2) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
With sodium hydroxide; methanesulfonic acid; paraformaldehyde In N-methyl-acetamide; dichloromethane

[2-(2-thyenyl)ethyl]amine (30433-91-1) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / methanol / 2 h / Reflux 2: sodium tetrahydroborate / methanol / 0 - 20 °C 3: N,N-dimethyl-formamide / 0 - 60 °C View Scheme

N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine (69061-17-2) + chloromethyl methyl ether (107-30-2) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
Stage #1: N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine; chloromethyl methyl ether In N,N-dimethyl-formamide at 0 - 60℃; Stage #2: With hydrogenchloride In ethanol

2-chloro-benzaldehyde (89-98-5) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / methanol / 2 h / Reflux 2: sodium tetrahydroborate / methanol / 0 - 20 °C 3: N,N-dimethyl-formamide / 0 - 60 °C View Scheme

C13H12ClNS (122853-32-1) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol / 0 - 20 °C 2: N,N-dimethyl-formamide / 0 - 60 °C View Scheme

2-thiophenethanol (5402-55-1) → ticlopidine hydrochloride (53885-35-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium carbonate / toluene / 3.5 h / 0 - 20 °C 2.1: toluene / 3 h / 85 °C 2.2: 4 h / 2 °C / pH 5 - 8.5 3.1: hydrogenchloride / water; 1,3-dioxane / 6 h / 90 °C View Scheme
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / toluene / 3.5 h / 0 - 20 °C 2.1: toluene / 3 h / 85 °C 2.2: 1 h / 20 °C / pH 8.5 3.1: hydrogenchloride / water; 1,3-dioxane / 6 h / 90 °C View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine / toluene / 3 h / 0 - 20 °C 2.1: toluene / 4 h / 20 - 85 °C 2.2: pH 8.5 3.1: hydrogenchloride / water; 1,3-dioxane / 9 h / 7 - 90 °C 3.2: 4 h / 4 °C View Scheme
Multi-step reaction with 3 steps 1.1: potassium carbonate / toluene / 3.5 h / 0 - 20 °C 2.1: toluene / 3 h / 85 °C 2.2: 4 h / 2 °C / pH 5 - 8.5 3.1: hydrogenchloride / water / 6 h / 90 °C View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine / toluene / 3.5 h / 0 - 25 °C 2.1: toluene / 4 h / 25 - 90 °C 2.2: 4 h / 2 °C / pH 5 3.1: hydrogenchloride / water / 6 h / 90 °C View Scheme

4-(3-(pyridin-2-ylthio)propyl)morpholine + ticlopidine hydrochloride (53885-35-1) → 4-(3-((2-((6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)methyl)phenyl)thio)propyl)morpholine

Conditions	Yield
Stage #1: ticlopidine hydrochloride With sodium hydrogencarbonate In water Inert atmosphere; Stage #2: 4-(3-(pyridin-2-ylthio)propyl)morpholine With bis(1,5-cyclooctadiene)nickel (0); 3,4-thiene-2,3-diylbis(dicyclohexylphosphine); zinc In toluene at 150℃; for 24h; Inert atmosphere; Glovebox; Sealed tube;	76%

Upstream product

• 646-06-0 1,3-DIOXOLANE 
• 60612-23-9 N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine hydrochloride 
• 505-23-7 1,3 dithiane 
• 54903-50-3 4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 108-20-3 di-isopropyl ether 
• 611-19-8 1-chloro-2-(chloromethyl)benzene 
• 18997-19-8 Chloromethyl pivalate 
• 69061-17-2 N-(2-chloro-benzyl)-2-(thien-2-yl)-ethylamine 
• 30433-91-1 [2-(2-thyenyl)ethyl]amine 
• 2053-29-4 methyleneamine 
• 107-30-2 chloromethyl methyl ether 
• 89-98-5 2-chloro-benzaldehyde 
• 122853-32-1 C₁₃H₁₂ClNS 
• 5402-55-1 2-thiophenethanol 

Relevant articles and documents

A method for preparing pyridine [...] of hydrochloric acid

The invention discloses a preparation method of ticlopidine hydrochloride. The preparation method comprises the following steps: A, adding a certain amount of reactive raw materials into a reaction container, and carrying out reaction at the temperature of 30-80 DEG C for 1-10 hours, wherein the raw materials include 2-thiophene ethylamine, methanal, a haloalkane solvent and a solid super acidic catalyst; B, cooling the solution of reaction to room temperature; C, adding a certain amount of a solid alkaline catalyst and 2-chlorobenzyl chloride into the solution of reaction, carrying out reaction at the temperature of 30-80 DEG C for 1-10 hours, stopping heating, and standing to precipitate; D, filtering to obtain a filtrate; and E, introducing hydrogen chloride into the filtrate to obtain ticlopidine hydrochloride. The solid super acidic catalyst and the solid alkaline catalyst are adopted by the preparation method, and the heterogeneous tandem reaction is carried out. The technology has the advantage of convenience in post-treatment, is easy to operate, can not cause corrosion to equipment and is economical, practical and environment-friendly, less three wastes are produced, and the solid acid and alkali can be reused.

Preparation method of ticlopidine hydrochloride

The invention provides a preparation method of ticlopidine hydrochloride. The preparation method comprises the following steps: reacting thiophene ethanol as a raw material with paratoluensulfonyl chloride at first under the action of an acid-binding agent so as to protect and activate hydroxyl radicals; then performing condensation reaction with o-chlorobenzylamine; and then under an acidic condition, performing ring-closing reaction with 1,3-dioxolane to obtain ticlopidine hydrochloride. The preparation method is mild in reaction condition, low in production cost, high in product yield and good in product quality, and can conveniently realize industrial production.

Method for synthesizing ticlopidine hydrochloride

The invention provides a method for synthesizing ticlopidine hydrochloride. The method comprises the following steps: by using thiopheneethanol as a raw material, under the action of an acid binding agent, firstly, performing a reaction on the thiopheneethanol and paratoluensulfonyl chloride to carry out protection and activation on hydroxy; performing a condensation reaction with chlorobenzylamine; then under an acid condition, performing a ring closing reaction with 1,3-dioxolane to obtain the ticlopidine hydrochloride. The method is mild in reaction condition, low in production cost, high in product yield and high in quality, and is convenient for industrial production.