3605-01-4

Basic information

• Product Name: 2-[4-(1,3-Benzodioxol-5-ylmethyl)piperazin-1-yl]pyrimidine
• Synonyms: PIRIBEDIL;Piribendyl;PIRIBEDIL(FORR&DONLY0;PIRIBEDIOL;ET-495;EU-4200;Trivastal;Trivastan
• CAS NO: 3605-01-4
• Molecular Formula: C₁₆H₁₈N₄O₂
• Molecular Weight: 298.34
• EINECS: 222-764-6
• Product Categories: API;Isotope labelled API
• Mol File: 3605-01-4.mol
• Article Data: 39

Chemical Properties

• Melting Point: 98°
• Boiling Point: 439.76°C (rough estimate)
• Flash Point: 237.665 °C
• Appearance: /
• Density: 1.1183 (rough estimate)
• Vapor Pressure: 5.54E-09mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 7.17±0.10(Predicted)
• Merck: 14,7493
• CAS DataBase Reference: 2-[4-(1,3-Benzodioxol-5-ylmethyl)piperazin-1-yl]pyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[4-(1,3-Benzodioxol-5-ylmethyl)piperazin-1-yl]pyrimidine(3605-01-4)
• EPA Substance Registry System: 2-[4-(1,3-Benzodioxol-5-ylmethyl)piperazin-1-yl]pyrimidine(3605-01-4)

Safety Data

• RTECS: UV9704000
• Hazardous Substances Data: 3605-01-4(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Originator

Trivastal, Eutherapie ,France,1969

Uses

Different sources of media describe the Uses of 3605-01-4 differently. You can refer to the following data:
1. Piribedil is an antiparkisonian agent that acts as a dopamine agonist. Piribedil also displays α2-adrenergic antagonist properties. Piribedil has also been shown to counteract age-related memory impai rment by improving memory and attention as well as increasing the velocity of psychomotor reactions and lability of nervous processes.
2. Piribedil is an antiparkisonian agent that acts as a dopamine agonist. Piribedil also displays α2-adrenergic antagonist properties. Piribedil has also been shown to counteract age-related memory impairment by improving memory and attention as well as increasing the velocity of psychomotor reactions and lability of nervous processes.

Manufacturing Process

To a solution of 21 g of 1-(3':4'-methylenedioxybenzyl)-piperazine in solution in 300 cc of anhydrous xylene there were added 28 g of anhydrous potassium carbonate and then 11.3 g of 2-chloropyrimidine. The suspension was then heated for 9 hours at boiling point (130°C). After this time, the mixture was cooled and extracted several times with 10% hydrochloric acid. The acid solution obtained was washed with ether and then rendered alkaline with potassium carbonate; the oily product which was separated was extracted with chloroform and this, after drying with potassium carbonate and evaporation, gave an oily residue weighing 20 g. By dissolution in boiling ethanol and crystallization, 15 g of crystals melting at 96°C were recovered.

Therapeutic Function

Vasodilator

InChI:InChI=1/C16H18N4O2.CH4O3S/c1-4-17-16(18-5-1)20-8-6-19(7-9-20)11-13-2-3-14-15(10-13)22-12-21-14;1-5(2,3)4/h1-5,10H,6-9,11-12H2;1H3,(H,2,3,4)

Synthetic route

piperonol (495-76-1) + N-(2-pyridinyl)piperazine (20980-22-7) → piribedil (3605-01-4)

Conditions	Yield
With 2,2,2-trifluoroethanol; chloro-(pentamethylcyclopentadienyl)-{5-methoxy-2-{1-[(4-methoxyphenyl)imino-N]ethyl}phenyl-C}-iridium(lll); potassium carbonate at 100℃; for 24h; Inert atmosphere; Sealed tube;	99%
With polystyrene supported triphenylphosphine ruthenium complex In toluene at 140℃; for 48h; Sealed tube; Flow reactor;	98%
With NiCuFeO(x) In 5,5-dimethyl-1,3-cyclohexadiene for 24h; Inert atmosphere; Sealed tube; Reflux;	93%

2-chloropyrimidine (1722-12-9) + 1-Piperonylpiperazine (32231-06-4) → piribedil (3605-01-4)

Conditions	Yield
With C50H61Cl2N3Pd; potassium tert-butylate In 1,4-dioxane at 100℃; for 2h;	98%
With C48H55ClN2Pd; sodium t-butanolate In 1,2-dimethoxyethane at 20℃; for 16h; Inert atmosphere; Sealed tube;	98%
With potassium carbonate In tetrahydrofuran for 2h; Reflux;	44%

benzo[d][1,3]dioxol-5-yl(4-(pyrimidin-2-yl)piperazin-1-yl)mathanone → piribedil (3605-01-4)

Conditions	Yield
With bis(trimethylsilyl)amide yttrium(III); 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In toluene at 100℃; for 24h; Sealed tube; Inert atmosphere; Schlenk technique;	93%

5-(chloromethyl)-1,3-benzodioxole (20850-43-5) + N-(2-pyridinyl)piperazine (20980-22-7) → piribedil (3605-01-4)

Conditions	Yield
With triethylamine In isopropyl alcohol at 20 - 50℃;	92%
With potassium carbonate In 5,5-dimethyl-1,3-cyclohexadiene at 130℃; for 9h;	52%
With triethylamine In isopropyl alcohol at 50℃; for 4.5h; Time;
With triethylamine In isopropyl alcohol at 20 - 50℃; for 2.5h; Time;	14.76 g

2,6-Dichloropyrimidine (3934-20-1) + 1-Piperonylpiperazine (32231-06-4) → piribedil (3605-01-4)

Conditions	Yield
With C34H52BrN3OPd In 1,4-dioxane at 90℃; for 3h; Inert atmosphere; Schlenk technique;	92%

piperonal (120-57-0) + N-(2-pyridinyl)piperazine (20980-22-7) → piribedil (3605-01-4)

Conditions	Yield
With formic acid; boron trifluoride diethyl etherate In acetonitrile at 85℃; for 5h; Green chemistry;	90%
With formic acid; triethylamine In water; tert-butyl alcohol at 100℃; for 14h;	88%
With solid supported cyanoborohydride In dichloromethane	86%

1,2-(methylenedioxy)-4-bromobenzene (2635-13-4) + 2-(4-methylpiperazin-1-yl)pyrimidine (145208-86-2) → piribedil (3605-01-4)

Conditions	Yield
In ethyl acetate for 4h; Reflux; Green chemistry;	127.6 g

piribedil (3605-01-4) → C16H14(2)H4N4O2

Conditions	Yield
With copper(l) iodide; tris(triphenylphosphine)ruthenium(II) chloride; potassium deuterohydroxide; water-d2; zinc In 1,4-dioxane at 80℃; for 16h; Inert atmosphere; Schlenk technique; chemoselective reaction;	99%

piribedil (3605-01-4) → C16H16(2)H2N4O2

Conditions	Yield
With copper(l) iodide; tris(triphenylphosphine)ruthenium(II) chloride; water-d2; zinc In 1,4-dioxane at 80℃; for 62h; Inert atmosphere; Schlenk technique; chemoselective reaction;	87%

triethyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)silane (745783-97-5) + piribedil (3605-01-4) → 2-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-4-(triethylsilyl)pyrimidine

Conditions	Yield
With 1,2-dimethoxyethane; potassium hexamethylsilazane for 3h; Inert atmosphere; regioselective reaction;	79%

Upstream product

• 94-53-1 Piperonylic acid 
• 20980-22-7 N-(2-pyridinyl)piperazine 
• 120-57-0 piperonal 
• 1722-12-9 2-chloropyrimidine 
• 32231-06-4 1-Piperonylpiperazine 
• 37589-10-9 sodium benzo[d][1,3]dioxol-5-yl(hydroxy)methanesulfonate 
• 3934-20-1 2,6-Dichloropyrimidine 
• 2635-13-4 1,2-(methylenedioxy)-4-bromobenzene 
• 145208-86-2 2-(4-methylpiperazin-1-yl)pyrimidine 
• 93-54-9 1-Phenyl-1-propanol 
• 20850-43-5 5-(chloromethyl)-1,3-benzodioxole 
• 780705-64-8 1-piperazinecarboxylic acid 4-(2-pyrimidinyl)-, 1,1-dimethylethyl ester 
• 495-76-1 piperonol 
• 64-18-6 formic acid 

Relevant articles and documents

A new method for the preparation of piribedil - A dopaminergic drug

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