499-04-7

Basic information

• Product Name: ARECAIDINE BUT-2-YNYL ESTER TOSYLATE
• Synonyms: N-METHYL-1,2,5,6-TETRAHYDROPYRIDINE-3-CARBOXYLIC ACID BUT-2-YNYL ESTER TOSYLATE;1,2,5,6-tetrahydro-1-methyl-3-pyridinecarboxylicaci;1,2,5,6-tetrahydro-1-methyl-3-pyridinecarboxylicacid;1,2,5,6-tetrahydro-1-methyl-nicotinicaci;arecaidine;arecaine;methylguvacine;ARECAIDINE BUT-2-YNYL ESTER TOSYLATE
• CAS NO: 499-04-7
• Molecular Formula: C₇H₁₁NO₂
• Molecular Weight: 365.44
• Product Categories: Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Neurochemicals;Pharmaceuticals;Acetylcholine receptor
• Mol File: 499-04-7.mol
• Article Data: 4

Chemical Properties

• Melting Point: 232°C (dec.)
• Boiling Point: 104-112℃ (14-16 Torr)
• Flash Point: 115.1±25.9℃
• Appearance: /
• Density: 1.166±0.06 g/cm3 (20 ºC 760 Torr)
• Vapor Pressure: 0.00245mmHg at 25°C
• Refractive Index: 1.5026 (estimate)
• Storage Temp.: Store at RT
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: pKa 9.07(H2O t=25)(Approximate)
• CAS DataBase Reference: ARECAIDINE BUT-2-YNYL ESTER TOSYLATE(CAS DataBase Reference)
• NIST Chemistry Reference: ARECAIDINE BUT-2-YNYL ESTER TOSYLATE(499-04-7)
• EPA Substance Registry System: ARECAIDINE BUT-2-YNYL ESTER TOSYLATE(499-04-7)

Safety Data

• Hazardous Substances Data: 499-04-7(Hazardous Substances Data)

Usage

Chemical Properties

Crystalline Solid

Uses

Different sources of media describe the Uses of 499-04-7 differently. You can refer to the following data:
1. A metabolite of Arecoline, a cholinergic agonist.
2. Arecaidine but-2-ynyl ester tosylate is a potent, selective mAChR M2 activator.

Biological Activity

Potent muscarinic agonist, 4.6-fold selective for M 2 receptors in the atrium versus those in the ileum.

Safety Profile

Mutation data reported. Whenheated to decomposition it emits toxic fumes of NOx.

InChI:InChI=1/C7H11NO2/c1-8-4-2-3-6(5-8)7(9)10/h3H,2,4-5H2,1H3,(H,9,10)

Synthetic route

arecoline hydrobromide (300-08-3) → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
Stage #1: arecoline hydrobromide With sodium carbonate In water pH=10 - 11; Stage #2: With water Reflux;	89%
With barium dihydroxide at 40℃; for 0.5h;
Multi-step reaction with 2 steps 1: aq. Na2CO3 / pH 10 - 11 2: 8.2 g / water / 24 h / Heating View Scheme
With hydrogenchloride; water Heating / reflux;

3-cyano-1-methyl-1,2,5,6-tetrahydropyridine (5657-66-9) → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With hydrogenchloride Erwaermen des Rueckstands mit Barytwasser;

arecoline (63-75-2) → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With hydrogen bromide
With water for 24h; Hydrolysis; Heating;	8.2 g

arecoline (63-75-2) → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxamide (5809-87-0)

Conditions	Yield
With ammonium hydroxide

1-methyl-4-oxo-piperidine-3-carboxylic acid methyl ester (13221-89-1, 56026-45-0) → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With aluminum nickel; ethanol Hydrogenation.Behandeln des Reaktionsprodukts mit HCl in Essigsaeure;

4-hydroxy-1-methyl-piperidine-3-carboxylic acid ethyl ester (37673-66-8) → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With hydrogenchloride

3-Carboxy-1-methylpyridiniumiodid (6138-42-7) → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With potassium borohydride; alkaline aqueous solution

Trigonelline (535-83-1) → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With sulfuric acid Electrolysis;

1-methyl-4-oxy-piperidine-carboxylic acid-(3)-ethyl ester → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With hydrogenchloride; potassium iodide
With hydrogen bromide

4t-chloro-1-methyl-piperidine-3r-carboxylic acid methyl ester → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With sodium hydroxide

arecoline → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

formaldehyd (50-00-0) + guvacine → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With formic acid at 155 - 160℃; im Rohr;

potassium methyl sulfate (562-54-9) + guvacine → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With sodium methylate at 140 - 150℃;

nicotinic acid methyl ester chloromethylate → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With hydrogenchloride; tin

trigonellin → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
With hydrogenchloride; tin

Trigonelline (535-83-1) + lead-cathodes + aqueous H2SO4 → 1,5-dimethyl-1,2,3,6-tetrahydro-pyridine (695-36-3) + 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + 1,3-dimethylpiperidine (695-35-2)

Conditions	Yield
Electrolysis;

ethyl 1-methyl-4-oxo-piperidin-3-carboxylate (25012-72-0) → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: lead-cathode; aqueous H2SO4 / elektrochemischen Reduktion 2: aqueous HCl View Scheme

3,3'-methylimino-di-propionic acid diethyl ester (6315-60-2) → 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaNH2; xylene 2: lead-cathode; aqueous H2SO4 / elektrochemischen Reduktion 3: aqueous HCl View Scheme

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) → (+)-1-methylpiperidine-3-carboxylic acid

Conditions	Yield
With C63H78IrNOP(2+)*C32H12BF24(1-); hydrogen In methanol at 60℃; under 4560.31 Torr; for 12h; Autoclave; enantioselective reaction;	98%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + dicyclohexyl-carbodiimide (538-75-0) → N-cyclohexyl-N-(cyclohexylcarbamoyl)-1-methyl-1,2,5,6-tetrahydropyridine-3-carboxamide

Conditions	Yield
With dmap; 1,1-Diphenylmethanol In dichloromethane; N,N-dimethyl-formamide at 0 - 70℃; for 1.5h;	69%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + sodium (4-bromophenyl)(4-fluorophenyl)methanolate → (4-bromophenyl)(4-fluorophenyl)methyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 0.5h; Stage #2: sodium (4-bromophenyl)(4-fluorophenyl)methanolate In N,N-dimethyl-formamide at 20℃; for 336h;	25%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) → benzhydryl 4-methylmorpholine-2-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 0.5h; Stage #2: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid In N,N-dimethyl-formamide at 20℃; for 18h;	24%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + benzhydrol sodium salt (1204-50-8) → benzhydryl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 0.25h; Stage #2: benzhydrol sodium salt In N,N-dimethyl-formamide at 20℃; for 18h;	19%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + triethylene glucol monomethyl ether (112-35-6) → 2-[2-(2-methoxyethoxy)ethoxy]ethyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide Stage #2: triethylene glucol monomethyl ether In N,N-dimethyl-formamide at 20℃; for 60h;	18%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + sodium furan-2-yl(phenyl)methanolate → furan-2-yl(phenyl)methyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 0.333333h; Stage #2: sodium furan-2-yl(phenyl)methanolate In N,N-dimethyl-formamide at 20℃; for 60h;	15%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + 11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (28797-48-0) → 2-oxo-2-(6-oxo-5,6-dihydro-11H-benzo[e]pyrido[3,2-b][1,4]diazepin-11-yl)ethyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With sodium hydride In N,N-dimethyl-formamide for 0.0166667h; Stage #2: 11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one With sodium iodide In N,N-dimethyl-formamide at 70℃; for 1h;	13%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + (R,R)-hydroxybenzoin (52340-78-0) → (1R,2R)-(+)-2-hydroxy-1,2-diphenylethyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 1h; Stage #2: (R,R)-hydroxybenzoin In N,N-dimethyl-formamide at 20℃; for 168h; stereoselective reaction;	13%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + Benzhydrylamine (91-00-9) → N-benzhydryl-1-methyl-1,2,5,6-tetrahydropyridine-3-carboxamide

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 1h; Stage #2: Benzhydrylamine In N,N-dimethyl-formamide at 20℃; for 18h;	12%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + sodium 4,4'-difluordiphenylmethanolate → bis(4-fluorophenyl)methyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 1h; Stage #2: sodium 4,4'-difluordiphenylmethanolate In N,N-dimethyl-formamide at 20℃; for 60h;	9%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + sodium 4,4'-dimethoxydiphenylmethanolate → bis(4-methoxyphenyl)methyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 1h; Stage #2: sodium 4,4'-dimethoxydiphenylmethanolate In N,N-dimethyl-formamide at 20℃; for 24h;	4%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + sodium bis(6-fluoropyridin-3-yl)methanolate → bis(6-fluoropyridin-3-yl)methyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 1h; Stage #2: sodium bis(6-fluoropyridin-3-yl)methanolate In N,N-dimethyl-formamide at 20℃; for 24h;	3%

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + 2-hydroxy-2-phenylacetophenone (119-53-9) → 2-oxo-1,2-diphenylethyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
Stage #1: 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 1h; Stage #2: 2-hydroxy-2-phenylacetophenone In N,N-dimethyl-formamide at 20℃; for 120h;	3%

propan-1-ol (71-23-8) + 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) → 1-methyl-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid propyl ester (5497-44-9)

Conditions	Yield
With hydrogenchloride

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + isopropyl alcohol (67-63-0) → 1-methyl-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid isopropyl ester (10558-56-2)

Conditions	Yield
With hydrogenchloride

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + butan-1-ol (71-36-3) → 1-methyl-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid butyl ester (5497-45-0)

Conditions	Yield
With hydrogenchloride

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) → arecoline (63-75-2)

Conditions	Yield
With hydrogenchloride

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) → Homoarecoline (28125-84-0)

Conditions	Yield
With hydrogenchloride

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) → N-methyl-1,2,5,6-tetrahydronicotinoyl chloride hydrochloride (74024-49-0)

Conditions	Yield
With thionyl chloride

morpholine (110-91-8) + 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) → 4-(1-methyl-1,2,5,6-tetrahydro-pyridine-3-carbonyl)-morpholine

Conditions	Yield
(i) SOCl2, benzene, (ii) /BRN= 102549/; Multistep reaction;

1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid (499-04-7) + propargyl alcohol (107-19-7) → Arecaidine propargyl ester hydrobromide (35516-99-5)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 12h; Heating; Yield given;

Upstream product

• 63-75-2 arecoline 
• 13221-89-1 1-methyl-4-oxo-piperidine-3-carboxylic acid methyl ester 
• 37673-66-8 4-hydroxy-1-methyl-piperidine-3-carboxylic acid ethyl ester 
• 535-83-1 Trigonelline 
• 300-08-3 arecoline hydrobromide 
• 50-00-0 formaldehyd 
• 562-54-9 potassium methyl sulfate 
• 25012-72-0 ethyl 1-methyl-4-oxo-piperidin-3-carboxylate 
• 6315-60-2 3,3'-methylimino-di-propionic acid diethyl ester 
• 5657-66-9 3-cyano-1-methyl-1,2,5,6-tetrahydropyridine 
• 6138-42-7 3-Carboxy-1-methylpyridiniumiodid 

Downstream Products

• 5497-44-9 Arecaidinpropylester 
• 10558-56-2 1-methyl-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid isopropyl ester 
• 5497-45-0 Arecaidin-n-butylester 
• 63-75-2 arecoline 
• 28125-84-0 Homoarecoline 
• 74-87-3 methylene chloride 
• 74-89-5 methylamine 
• 59826-28-7 1-Methyl-1,2,5,6-tetrahydro-pyridine-3-carbonyl chloride 
• 952480-19-2 (R)-1-methylpiperidine-3-carboxylic acid 
• 145678-68-8 (S)-N-methylnipecotic acid 

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