179474-79-4

Basic information

• Product Name: 1-(3-Methoxypropyl)-4-piperidinamine
• Synonyms: 1-(3-Methoxypropyl)-4-piperidinamine;4-AMino-1-(3-Methoxypropyl)piperidine;4-AMino-1-(3-Methoxypropy...;4-PiperidinaMine, 1-(3-Methoxypropyl)-;1-(3-Methoxypropyl)piperidin-4-aMine;Prucalopride Succinate interMediate B;1-(3-Methoxypropyl)-4-piperidimine
• CAS NO: 179474-79-4
• Molecular Formula: C₉H₂₀N₂O
• Molecular Weight: 172.2679
• EINECS: 1592732-453-0
• Mol File: 179474-79-4.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 249℃
• Flash Point: 105℃
• Appearance: /
• Density: 0.946
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 10.49±0.20(Predicted)
• CAS DataBase Reference: 1-(3-Methoxypropyl)-4-piperidinamine(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(3-Methoxypropyl)-4-piperidinamine(179474-79-4)
• EPA Substance Registry System: 1-(3-Methoxypropyl)-4-piperidinamine(179474-79-4)

Safety Data

• Hazardous Substances Data: 179474-79-4(Hazardous Substances Data)

Usage

Uses

1-(3-Methoxypropyl)-4-piperidinamine is a useful synthetic intermediate in the synthesis of Prucalopride Succinate (P838950); a selective 5-HT4 receptor agonist used effective for chronic constipation, but is not currently approved in the U.S. Prucalopride is approved for the treatment of chronic constipation in Europe.

Synthetic route

1-[3-(methyloxy)propyl]-4-piperidinecarboxamide (519147-89-8) → 4-amino-1-(3-methoxypropyl)piperidine (179474-79-4)

Conditions	Yield
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; potassium hydroxide In water; acetonitrile at 5 - 25℃; for 13h;	83%

C22H28N2O → 4-amino-1-(3-methoxypropyl)piperidine (179474-79-4)

Conditions	Yield
With hydrogenchloride In water at 0 - 20℃; pH=1 - 2;	81%

ethyl 1-(3-methoxy-propyl)-piperidin-4-carboxylate (1249604-45-2) → 4-amino-1-(3-methoxypropyl)piperidine (179474-79-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonia / methanol / 60 °C 2: potassium hydroxide; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / water; acetonitrile / 13 h / 5 - 25 °C View Scheme

methyl-1-(3-methoxypropyl)piperidine-4-carboxylate → 4-amino-1-(3-methoxypropyl)piperidine (179474-79-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonium hydroxide / 60 °C 2: potassium hydroxide; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / water; acetonitrile / 13 h / 5 - 25 °C View Scheme

4-aminopiperidine (13035-19-3) → 4-amino-1-(3-methoxypropyl)piperidine (179474-79-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: boron trifluoride diethyl etherate / toluene / Reflux 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 2.2: 3 h / 20 °C 3.1: hydrogenchloride / water / 0 - 20 °C / pH 1 - 2 View Scheme

4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) + succinic acid (110-15-6) + 4-amino-5-chloro-2,3-dihydrobenzo[b]furan-7-carboxylic acid (123654-26-2) → prucalopride succinic acid

Conditions	Yield
Stage #1: 4-amino-5-chloro-2,3-dihydrobenzo[b]furan-7-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran for 1.5h; Stage #2: 4-amino-1-(3-methoxypropyl)piperidine In tetrahydrofuran at 45℃; for 4h; Stage #3: succinic acid In ethanol at 20℃; for 2h; Solvent; Reagent/catalyst; Temperature;	94%

4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) + 4-amino-5-chloro-2,3-dihydrobenzo[b]furan-7-carboxylic acid (123654-26-2) → prucalopride (179474-81-8)

Conditions	Yield
Stage #1: 4-amino-5-chloro-2,3-dihydrobenzo[b]furan-7-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran for 0.416667h; Stage #2: 4-amino-1-(3-methoxypropyl)piperidine In tetrahydrofuran at 45 - 50℃; for 4h;	85%

4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) + 8-chloro-3-methyl-1,7-naphthyridin-2(1H)-one → C18H26N4O2

Conditions	Yield
With Caddick catalyst In 2-methyltetrahydrofuran at 20 - 140℃; for 0.5h; Microwave irradiation;	19%

4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) → 5-AMINO-6-CHLORO-2-METHYL-N-{1-[3-(METHOXY)PROPYL]-4-PIPERIDINYL}IMIDAZO[1,2-a]PYRIDINE-8-CARBOXAMIDE (519147-79-6)

5-amino-6-chloro-2-ethylimidazo[1,2-a]pyridine-8-carboxylic acid (519147-96-7) + 4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) → 5-AMINO-6-CHLORO-2-ETHYL-N-{1-[3-(METHOXY)PROPYL]-4-PIPERIDINYL}IMIDAZO[1,2-a]PYRIDINE-8-CARBOXAMIDE (519148-35-7)

Conditions	Yield
In 5-Amino-N-[(1-butyl-4-piperidinyl)methyl]-6-chloro-2-methylimidazo

4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) + 5-amino-6-chloro-2-propylimidazo[1,2-a]pyridine-8-carboxylic acid (519148-01-7) → 5-amino-6-chloro-2-propyl-N-{1-[3-(methoxy)propyl]-4-piperidinyl}imidazo[1,2-a]pyridine-8-carboxamide (519148-03-9)

Conditions	Yield
In 5-Amino-N-[(1-butyl-4-piperidinyl)methyl]-6-chloro-2-methylimidazo

4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) + 3-(3-t-butyl-5-(3-(naphthalen-1-yl)ureido)-1H-pyrazol-1-yl)benzoic acid (872171-59-0) → C34H42N6O3 (1254308-91-2)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate

4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) → prucalopride succinic acid

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.42 h 1.2: 4 h / 45 - 50 °C 2.1: ethanol / 3 h / 40 °C View Scheme

4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) + 4-amino-5-chloro-7-aldehyde-2,3-dihydrobenzofuran → prucalopride (179474-81-8)

Conditions	Yield
With tert.-butylhydroperoxide; calcium carbonate pentahydrate In acetonitrile at 80℃; for 8h;	36.5 g

4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) + 4-amino-5-chloro-7-hydroxymethyl-2,3-dihydrobenzofuran → prucalopride (179474-81-8)

Conditions	Yield
With tert.-butylhydroperoxide; zinc(II) iodide In acetonitrile at 70℃; for 5h;	33.6 g

4-amino-1-(3-methoxypropyl)piperidine (179474-79-4) + 7-(4-((tert-butoxycarbonyi)(phenethyl)amino)piperidin-1-yl)-2-oxo-2H-chromen-4-yl-trifluoromethanesulfonate → C36H50N4O5

Conditions	Yield
With triethylamine In 1,4-dioxane Reflux;

Upstream product

• 13035-19-3 4-aminopiperidine 
• 519147-89-8 1-[3-(methyloxy)propyl]-4-piperidinecarboxamide 
• 1249604-45-2 ethyl 1-(3-methoxy-propyl)-piperidin-4-carboxylate 

Downstream Products

• 179474-85-2 prucalopride succinate 
• 179474-81-8 prucalopride 

Relevant articles and documents

A process for preparing 1 - (3 - a oxygen propyl) piperidine - 4 - amine (by machine translation)

The invention discloses a method for preparing 1-(3-methoxypropyl)-4-piperidinamine. The method includes the following steps: the raw material, namely 4-aminopiperdine is adopted, primary amine is selectively protected by benzophenone based on the difference of chemical properties of primary amine and secondary amine, free secondary amine is subjected to proton abstraction, then the free secondary amine subjected to proton abstraction reacts with 3-methoxy-bromopropane, under the acid condition, the protecting group is removed, and finally, the product is obtained. The synthetic process is simple to operate, besides, the removed protecting group subjected to simple treatment can be recycled, and industrial enlarged production is facilitated.