36421-15-5

Basic information

• Product Name: N-(3-chloropropyl)dibutylamine
• Synonyms: N-(3-chloropropyl)dibutylamine;NSC51133;Einecs 253-027-7;1-Dibutylamino-3-chloropropane;1-Chloro-3-di-N-butylaminopropane;N-butyl-N-(3-chloropropyl)butan-1-aMine;Dronedarone Hydrochloride IMpurity F;Dibutyl(3-chloropropyl)aMine
• CAS NO: 36421-15-5
• Molecular Formula: C₁₁H₂₄ClN
• Molecular Weight: 205.76796
• EINECS: 253-027-7
• Product Categories: API
• Mol File: 36421-15-5.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 253.2 °C at 760 mmHg
• Flash Point: 106.9 °C
• Appearance: /
• Density: 0.899 g/cm³
• Vapor Pressure: 0.0185mmHg at 25°C
• Refractive Index: 1.45
• Storage Temp.: 2-8°C
• PKA: 9.39±0.50(Predicted)
• CAS DataBase Reference: N-(3-chloropropyl)dibutylamine(CAS DataBase Reference)
• NIST Chemistry Reference: N-(3-chloropropyl)dibutylamine(36421-15-5)
• EPA Substance Registry System: N-(3-chloropropyl)dibutylamine(36421-15-5)

Safety Data

• Hazardous Substances Data: 36421-15-5(Hazardous Substances Data)

Usage

Uses

N-Butyl-N-(3-chloropropyl)butan-1-amine acts as a reagent in the process for the production of dronedarone hydrochloride, an antiarrhythmia drug. Impurity of Butoprozine which is an antiarrhythmic drug.

InChI:InChI=1/C11H24ClN/c1-3-5-9-13(10-6-4-2)11-7-8-12/h3-11H2,1-2H3

Synthetic route

1-chloro-3-(di-n-butylamino)-propane hydrochloride → dibutyl-(3-chloro-propyl)-amine (36421-15-5)

Conditions	Yield
With ammonia In water at 20 - 24℃; for 1.41667h; pH=11;	99.4%
With ammonia In water at 18 - 24℃; for 0.75h;	99.4%
With ammonia In water at 20℃; for 0.25h;	9.99 g
With ammonium hydroxide In water at 20 - 25℃; for 0.25h;

3-dibutylaminopropanol (2050-51-3) → dibutyl-(3-chloro-propyl)-amine (36421-15-5)

Conditions	Yield
With thionyl chloride In chloroform for 7h; Reflux;	94%
With thionyl chloride In chloroform at 20℃; for 1h; Reflux; Inert atmosphere;	89%
With thionyl chloride; chloroform
With thionyl chloride; benzene
With hydrogenchloride; thionyl chloride In chloroform

dibutylamine (111-92-2) + 1-chloro-3-hydroxypropane (627-30-5) → dibutyl-(3-chloro-propyl)-amine (36421-15-5)

Conditions	Yield
With thionyl chloride In chloroform; water; dimethyl sulfoxide	58%

dibutylamine (111-92-2) + 1,3-chlorobromopropane (109-70-6) → dibutyl-(3-chloro-propyl)-amine (36421-15-5)

Conditions	Yield
With benzene

dibutylamine (111-92-2) → dibutyl-(3-chloro-propyl)-amine (36421-15-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium tetrafluoroborate / acetonitrile / 4 h / 20 °C / Inert atmosphere 2: thionyl chloride / chloroform / 1 h / 20 °C / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: methanol / 8 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 8 h / 20 °C 3: thionyl chloride / chloroform / 7 h / Reflux View Scheme

3-dibutylaminopropionic acid ethyl ester (20120-23-4) → dibutyl-(3-chloro-propyl)-amine (36421-15-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 8 h / 20 °C 2: thionyl chloride / chloroform / 7 h / Reflux View Scheme

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + methyl 4-hydroxylbenzoate (99-76-3) → 4-[3-(dibutylamino)propoxy]benzoic acid

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 25 - 100℃; for 1.16667h;	99.7%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-[3-(dibutylamino)propoxyl]benzoate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 98 - 102℃; for 1h;	99.7%

2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran (141645-16-1) + dibutyl-(3-chloro-propyl)-amine (36421-15-5) → (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (141645-23-0)

Conditions	Yield
Stage #1: 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran With potassium carbonate In toluene at 25 - 110℃; for 0.5h; Large scale; Stage #2: dibutyl-(3-chloro-propyl)-amine In toluene Temperature; Solvent; Reflux; Large scale;	99.5%
Stage #1: 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran With potassium carbonate In acetonitrile for 0.5h; Stage #2: dibutyl-(3-chloro-propyl)-amine In acetonitrile Reflux;	91%
Stage #1: 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran With potassium carbonate In acetonitrile for 0.5h; Reflux; Stage #2: dibutyl-(3-chloro-propyl)-amine In acetonitrile Reflux;	91%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (1-Bromo-2-ethyl-indolizin-3-yl)-(3,5-dichloro-4-hydroxy-phenyl)-methanone (77833-28-4) → (1-Bromo-2-ethyl-indolizin-3-yl)-[3,5-dichloro-4-(3-dibutylamino-propoxy)-phenyl]-methanone; compound with oxalic acid (79283-47-9)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	95.1%

methyl 2-butyl-3-(4-hydroxybenzoyl)-1-benzofuran-5-carboxylate (401840-53-7) + dibutyl-(3-chloro-propyl)-amine (36421-15-5) → Methyl 2-butyl-3-[4-[3-dibutylaminopropoxy]benzoyl]-1-benzofuran-5-carboxylate (401838-64-0)

Conditions	Yield
With potassium carbonate In butanone for 22h; Heating / reflux;	94%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + 2-n-butyl-3-(4-hydroxy-benzoyl)-5-bis-(methylsulfonamido)-benzofuran (1352731-07-7) → N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)-benzoyl)benzofuran-5-yl)-N-(methylsulfonyl)methanesulfonamide (141626-57-5)

Conditions	Yield
With potassium carbonate In butanone for 8h;	93.5%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (1-Bromo-2-methyl-indolizin-3-yl)-(3-chloro-4-hydroxy-phenyl)-methanone (77832-91-8) → (1-Bromo-2-methyl-indolizin-3-yl)-[3-chloro-4-(3-dibutylamino-propoxy)-phenyl]-methanone; compound with oxalic acid (79282-28-3)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	93.3%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (3,5-Dibromo-4-hydroxy-phenyl)-(2-methyl-indolizin-3-yl)-methanone (77823-57-5) → [3,5-Dibromo-4-(3-dibutylamino-propoxy)-phenyl]-(2-methyl-indolizin-3-yl)-methanone; compound with oxalic acid (79285-48-6)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	92.7%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + 2-Isopropyl-3-(4-hydroxybenzenesulphonyl)pyrazolo[1,5-a]pyridine (121346-57-4) → 2-isopropyl-3-{4-[3-(di-n-butylamino)-propyloxy]benzenesulphonyl}pyrazolo[1,5-a]pyridine oxalate

Conditions	Yield
With oxalic acid; potassium carbonate In hexane; ethyl acetate; N,N-dimethyl-formamide	92%
With oxalic acid; potassium carbonate In hexane; ethyl acetate; N,N-dimethyl-formamide	92%
With oxalic acid; potassium carbonate In hexane; ethyl acetate; N,N-dimethyl-formamide	92%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + 2-Isopropyl-3-(4-hydroxybenzenesulphonyl)pyrazolo[1,5-a]pyridine (121346-57-4) → 2-isopropyl-3-[4-}3-[N-methyl-N-(3,4-dimethoxy-β-phenethyl)amino]propyloxy}benzenesulphonyl]pyrazolo(1,5-a]pyridine oxalate + 2-isopropyl-3-{4-[3-(di-n-butylamino)-propyloxy]benzenesulphonyl}pyrazolo[1,5-a]pyridine oxalate

Conditions	Yield
With oxalic acid; potassium carbonate In hexane; ethyl acetate; N,N-dimethyl-formamide	A n/a B 92%

4-bromo-phenol (106-41-2) + dibutyl-(3-chloro-propyl)-amine (36421-15-5) → N-(3-(4-bromophenoxy)propyl)-N-butylbutan-1-amine (627040-50-0)

Conditions	Yield
With caesium carbonate; sodium iodide In acetonitrile at 20 - 60℃; for 23h; Inert atmosphere;	92%
With potassium carbonate In N,N-dimethyl-formamide	90%
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 1.33333h;	90%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (1-Chloro-2-methyl-indolizin-3-yl)-(4-hydroxy-phenyl)-methanone (77832-66-7) → (1-Chloro-2-methyl-indolizin-3-yl)-[4-(3-dibutylamino-propoxy)-phenyl]-methanone; compound with oxalic acid (79285-57-7)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	91.7%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (3-Bromo-4-hydroxy-phenyl)-(2-ethyl-1-methyl-indolizin-3-yl)-methanone (88274-10-6) → 1-Methyl-2-ethyl-3-[4-(3-di-n-butylaminopropyl)-oxy-3-bromo-benzoyl]-indolizine (86114-04-7)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	90.2%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (3-Bromo-4-hydroxy-phenyl)-[2-(4-chloro-phenyl)-indolizin-3-yl]-methanone (77823-30-4) → [3-Bromo-4-(3-dibutylamino-propoxy)-phenyl]-[2-(4-chloro-phenyl)-indolizin-3-yl]-methanone; compound with oxalic acid (79285-88-4)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	89.7%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (2,6-dibutylbenzo[1,2-b:5,4-b']difuran-3,5-diyl)bis((4-hydroxyphenyl)methanone) → (2,6-dibutylbenzo[1,2-b:5,4-b']difuran-3,5-diyl)bis((4-(3-(dibutylamino)propoxy)phenyl)methanone)

Conditions	Yield
Stage #1: (2,6-dibutylbenzo[1,2-b:5,4-b']difuran-3,5-diyl)bis((4-hydroxyphenyl)methanone) With potassium carbonate In toluene at 25 - 30℃; for 0.5h; Stage #2: dibutyl-(3-chloro-propyl)-amine In toluene at 25 - 30℃; for 5h;	89.5%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (3-Chloro-4-hydroxy-phenyl)-(2-methyl-indolizin-3-yl)-methanone (77823-36-0) → [3-Chloro-4-(3-dibutylamino-propoxy)-phenyl]-(2-methyl-indolizin-3-yl)-methanone; compound with oxalic acid (79285-98-6)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	88.1%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (1-Bromo-2-phenyl-indolizin-3-yl)-(3,5-dibromo-4-hydroxy-phenyl)-methanone (77833-12-6) → (1-Bromo-2-phenyl-indolizin-3-yl)-[3,5-dibromo-4-(3-dibutylamino-propoxy)-phenyl]-methanone; compound with oxalic acid (79283-37-7)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	87.7%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (1-Bromo-2-methyl-indolizin-3-yl)-(3,5-dibromo-4-hydroxy-phenyl)-methanone (77833-06-8) → (1-Bromo-2-methyl-indolizin-3-yl)-[3,5-dibromo-4-(3-dibutylamino-propoxy)-phenyl]-methanone; compound with oxalic acid (79283-33-3)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	86.7%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + [2-(4-Bromo-phenyl)-indolizin-3-yl]-(3,5-dichloro-4-hydroxy-phenyl)-methanone (77832-51-0) → [2-(4-Bromo-phenyl)-indolizin-3-yl]-[3,5-dichloro-4-(3-dibutylamino-propoxy)-phenyl]-methanone; compound with oxalic acid (79283-31-1)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	86.7%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (3-Bromo-4-hydroxy-phenyl)-(1-bromo-2-p-tolyl-indolizin-3-yl)-methanone (77832-82-7) → [3-Bromo-4-(3-dibutylamino-propoxy)-phenyl]-(1-bromo-2-p-tolyl-indolizin-3-yl)-methanone; compound with oxalic acid (79286-49-0)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	86.5%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (3-Bromo-4-hydroxy-phenyl)-(2-butyl-indolizin-3-yl)-methanone (77823-26-8) → [3-Bromo-4-(3-dibutylamino-propoxy)-phenyl]-(2-butyl-indolizin-3-yl)-methanone; compound with oxalic acid (79285-79-3)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	86.3%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + 1-bromo-2-(4-fluoro-phenyl)-3-(3-bromo-4-hydroxy-benzoyl)-indolizine (77832-84-9) → [3-Bromo-4-(3-dibutylamino-propoxy)-phenyl]-[1-bromo-2-(4-fluoro-phenyl)-indolizin-3-yl]-methanone; compound with oxalic acid (79286-50-3)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	86%

2-butyl-3-(4-hydroxybenzoyl)-5-hydroxymethyl-1-benzofuran (401840-64-0) + dibutyl-(3-chloro-propyl)-amine (36421-15-5) + oxalic acid (144-62-7) → 2-Butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-hydroxymethyl-1-benzofuran Oxalate

Conditions	Yield
Stage #1: 2-butyl-3-(4-hydroxybenzoyl)-5-hydroxymethyl-1-benzofuran; dibutyl-(3-chloro-propyl)-amine With potassium carbonate In butanone for 6h; Heating / reflux; Stage #2: oxalic acid In methanol	85.5%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + [2-(3-Bromo-phenyl)-indolizin-3-yl]-(3-chloro-4-hydroxy-phenyl)-methanone (77823-42-8) → [2-(3-Bromo-phenyl)-indolizin-3-yl]-[3-chloro-4-(3-dibutylamino-propoxy)-phenyl]-methanone; compound with oxalic acid (79286-16-1)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	85.3%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + 2-tert-Butyl-1-(4-hydroxybenzenesulphonyl)indolizine (114432-37-0) → SR 33541 (114432-66-5)

Conditions	Yield
With potassium carbonate In butanone for 24h; Heating;	85%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (2-Ethyl-indolizin-3-yl)-(4-hydroxy-3-methoxy-phenyl)-methanone (77823-51-9) → [4-(3-Dibutylamino-propoxy)-3-methoxy-phenyl]-(2-ethyl-indolizin-3-yl)-methanone; compound with oxalic acid (79283-82-2)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	84.9%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (1-Bromo-2-ethyl-indolizin-3-yl)-(4-hydroxy-3-methoxy-phenyl)-methanone (77823-54-2) → (1-Bromo-2-ethyl-indolizin-3-yl)-[4-(3-dibutylamino-propoxy)-3-methoxy-phenyl]-methanone; compound with oxalic acid (79283-90-2)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	84.8%

dibutyl-(3-chloro-propyl)-amine (36421-15-5) + (1-Bromo-2-propyl-indolizin-3-yl)-(3-chloro-4-hydroxy-phenyl)-methanone (77832-93-0) → (1-Bromo-2-propyl-indolizin-3-yl)-[3-chloro-4-(3-dibutylamino-propoxy)-phenyl]-methanone; compound with oxalic acid (79282-34-1)

Conditions	Yield
With potassium carbonate In acetone for 20h; Heating;	84.4%

Upstream product

• 111-92-2 dibutylamine 
• 109-70-6 1.3-chlorobromopropane 
• 627-30-5 1-chloro-3-hydroxypropane 
• 20120-23-4 3-dibutylaminopropionic acid ethyl ester 
• 115555-77-6 1-chloro-3-(di-n-butylamino)-propane hydrochloride 
• 2050-51-3 3-dibutylaminopropanol 

Downstream Products

• 6344-40-7 2-(3-dibutylamino-propyl)-acetoacetic acid ethyl ester 
• 5417-24-3 4-dibutylamino-butyronitrile 
• 78186-54-6 benzilic acid-(3-dibutylamino-propyl ester) 
• 437651-42-8 methyl 4-[3-(dibutylamino)propoxyl]benzoate 
• 1278585-69-5 N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)acetamide 
• 1338547-31-1 ethyl 4-[3-(di-n-butylamino)-propoxyl]-benzoate 
• 1333493-68-7 1-{4-[3-(di-n-butylamino)propoxy]phenyl}-1,3-heptanedione 
• 141645-23-0 (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone 
• 1356411-44-3 C₃₀H₄₃N₃O₅ 
• 212651-58-6 4-(3-dibutylaminopropyl)oxyaniline 
• 114604-53-4 (6-Bromo-imidazo[1,2-a]pyridin-3-yl)-[4-(3-dibutylamino-propoxy)-phenyl]-methanone 

Relevant articles and documents

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Convergent synthesis of dronedarone, an antiarrhythmic agent

We have developed a convergent synthesis of dronedarone, an antiarrhythmic agent. The key steps of the process are the construction of a benzofuran skeleton by iodocyclization and the carbonylative Suzuki-Miyaura cross-coupling for biaryl ketone formation. This synthetic route required only eight steps from 2-amino-4-nitrophenol in 23% overall yield.

PROCESS FOR PREPARING BENZOFURAN DERIVATIVES SUBSTITUTED AT POSITION 5

The disclosure relates to a process for preparing benzofuran derivatives of general formula I: in which R, R1, and R2 are as defined in the disclosure; by coupling the hydroxylamine with a diketone of general formula III: in order to form an oxime that is then cyclized by heating in order to form the desired compound.