276863-95-7

Basic information

• Product Name: 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile
• Synonyms: 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile;3-(4-Chloro-1-oxobutyl)-1H-indole-5-carbonitrile;3-(4-Chloro-1-oxobutyl)indole-5-carbonitrile
• CAS NO: 276863-95-7
• Molecular Formula: C₁₃H₁₁ClN₂O
• Molecular Weight: 246.69224
• EINECS: 1806241-263-5
• Mol File: 276863-95-7.mol
• Article Data: 18

Chemical Properties

• Melting Point: 169-170 °C
• Boiling Point: 489.85 °C at 760 mmHg
• Flash Point: 250.053 °C
• Appearance: /
• Density: 1.31
• Storage Temp.: 2-8°C
• Solubility: Dimethyl Sulfoxide, Hot Methanol
• PKA: 14.07±0.30(Predicted)
• CAS DataBase Reference: 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile(276863-95-7)
• EPA Substance Registry System: 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile(276863-95-7)

Safety Data

• Hazardous Substances Data: 276863-95-7(Hazardous Substances Data)

Usage

Description

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile is an organic compound characterized by its light green solid appearance. It is a derivative of indole, a heterocyclic aromatic organic compound, with a chlorobutanoyl group attached to the 3-position and a nitrile group at the 5-position. 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile is known for its potential applications in the pharmaceutical industry, particularly in the development of drugs targeting the serotonin system.

Uses

Used in Pharmaceutical Industry:
3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile is used as a reactant for the preparation of dual 5-HT1A receptor agonists and serotonin reuptake inhibitors. Its chemical structure allows it to interact with the serotonin system, which plays a crucial role in various physiological processes and is often targeted in the treatment of mood disorders, anxiety, and other conditions.
As a reactant in the synthesis of these dual-action compounds, 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile contributes to the development of medications that can potentially provide more effective treatment options for patients suffering from serotonin-related disorders. The compound's ability to modulate the serotonin system through both agonist and reuptake inhibitor actions makes it a valuable asset in the pharmaceutical industry's ongoing efforts to create more effective and targeted therapies.

Synthetic route

1H-indole-5-carbonitrile (15861-24-2) + 4-Chlorobutanoyl chloride (4635-59-0) → 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 0 - 20℃;	93%
With titanium tetrachloride In chloroform at 0℃; for 20h; Solvent; Temperature;	90%
Stage #1: 4-Chlorobutanoyl chloride With aluminum (III) chloride In 1,2-dichloro-ethane at 0℃; for 1h; Stage #2: 1H-indole-5-carbonitrile In 1,2-dichloro-ethane at 0 - 20℃; for 2.5h;	87.4%

1H-indole-5-carbonitrile (15861-24-2) + 4-Chlorobutanoyl chloride (4635-59-0) → C13H11ClN2O + 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7)

Conditions	Yield
With isobutylaluminum dichloride In dichloromethane Friedel-Crafts Acylation;

SD-169 (1670-87-7) → 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / dichloromethane / 1 h / 5 °C / Cooling with ice; Large scale 1.2: 20 °C / Cooling with ice; Large scale 2.1: trichlorophosphate / dichloromethane / 10 °C / Cooling with ice; Large scale View Scheme

5-aminocarbonyl-3-(4-chlorobutyryl)indole → 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7)

Conditions	Yield
With trichlorophosphate In dichloromethane at 10℃; Cooling with ice; Large scale;	51 kg

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
With chloro-trimethyl-silane; sodium cyanoborohydride In acetonitrile at 0 - 30℃;	87.2%
Stage #1: 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile With aluminum (III) chloride In tetrahydrofuran for 0.5h; Cooling with ice; Stage #2: With sodium tetrahydroborate In tetrahydrofuran Reagent/catalyst;	80%
With iron(III) chloride; borane-THF; hydrogen In tetrahydrofuran at 20℃; Reagent/catalyst; Temperature; Inert atmosphere; Flow reactor;	71%

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) + 5-(1-piperazinyl)benzofuran-2-carboxamide (183288-46-2) → vilazodone N-oxide

Conditions	Yield
With triethylamine; potassium iodide In N,N-dimethyl-formamide at 20 - 90℃; for 49h; Inert atmosphere;	85%
With tributyl-amine In 1-methyl-pyrrolidin-2-one at 25 - 130℃; for 24h;	7%

2-Naphthalenesulfonyl chloride (93-11-8) + 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-(4-chlorobutyryl)-1-(naphthalen-2-yl-sulfonyl)-1H-indole-5-carbonitrile

Conditions	Yield
Stage #1: 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Stage #2: 2-Naphthalenesulfonyl chloride In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	82%

p-toluenesulfonyl chloride (98-59-9) + 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 1-p-toluenesulfonyl-3-(4-chlorobutyryl)-5-cyanoindole (1398358-62-7)

Conditions	Yield
With sodium hydroxide In dichloromethane at 20℃; for 5h;	81%

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-(4-hydroxybutanoyl)-1H-indole-5-carbonitrile

Conditions	Yield
With triethylamine In water; acetonitrile at 80 - 85℃; for 5h;	81%

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-(4-hydroxybutyl)-1H-indole-5-carbonitrile (914927-40-5)

Conditions	Yield
With sodium tetrahydroborate; isopropyl alcohol at 0 - 80℃; for 6h;	80%
With sodium tetrahydroborate In isopropyl alcohol at 80℃; for 6h;	80.6%
With sodium tetrahydroborate In isopropyl alcohol at 0 - 80℃; for 6h;	80%
With sodium tetrahydroborate; isopropyl alcohol at 0 - 80℃; for 6h; Inert atmosphere;	80%
With sodium tetrahydroborate; isopropyl alcohol at 0 - 80℃; for 6h;	80%

1-Naphthalenesulfonyl chloride (85-46-1) + 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-(4-chlorobutyryl)-1-(naphthalen-1-yl-sulfonyl)-1H-indole-5-carbonitrile

Conditions	Yield
Stage #1: 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Stage #2: 1-Naphthalenesulfonyl chloride In N,N-dimethyl-formamide at 0 - 20℃;	76%

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-(4-chloro-1-hydroxy-butyl)-1H-indol-5-carbonitrile (1451194-34-5)

Conditions	Yield
With sodium tetrahydroborate; water; sodium hydroxide In tetrahydrofuran at 30 - 35℃; for 3h;	73.5%
With sodium tetrahydroborate; water; sodium hydroxide In tetrahydrofuran at 30 - 35℃; for 3h;	73.5%

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-{4-[4-(4-cyano-phenyl)-piperazin-1-yl]-butyl}-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-[4-(4-benzo[1,3]dioxol-5-yl-piperazin-1-yl)-butyl]-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: 60 percent / K2CO3; KI / dimethylformamide / 12 h / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-{4-[4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-piperazin-1-yl]-butyl}-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-(4-(4-(2-oxo-2H-1-benzopyran-6-yl)piperazin-1-yl)butyl)indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-{4-[4-(2-cyano-benzofuran-5-yl)-piperazin-1-yl]-butyl}-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → vilazodone (163521-12-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; Et3N / acetonitrile / 12 h / Heating 3: KOH / methanol / 3 h / Heating 4: 72 percent / 1-methyl-2-chloropyridinium iodide; Et2NiPr; NH3(g) / 1-methyl-pyrrolidin-2-one View Scheme
Multi-step reaction with 3 steps 1: sodium bis(2-methoxyethoxy)aluminium dihydride / tetrahydrofuran 2: potassium carbonate / acetonitrile 3: potassium hydroxide / methanol View Scheme
Multi-step reaction with 4 steps 1.1: sodium bis(2-methoxyethoxy)aluminium dihydride / tetrahydrofuran 2.1: potassium carbonate / acetonitrile 3.1: potassium hydroxide / methanol 4.1: 1,1'-carbonyldiimidazole / methanol / 1 h / 20 °C / Reflux; Large scale 4.2: 0.5 h / Large scale View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-[4-(4-phenyl-piperazin-1-yl)-butyl]-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-{4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-butyl}-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-[4-(4-p-methoxyphenylpiperazino)butyl]-5-cyanoindole (143612-66-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-{4-[4-(4-fluoro-phenyl)-piperazin-1-yl]-butyl}-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-[4-(4-p-hydroxyphenylpiperazino)butyl]-5-cyanoindole

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-[4-(4-benzofuran-5-yl-piperazin-1-yl)-butyl]-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-[4-(4-benzo[1,2,5]thiadiazol-4-yl-piperazin-1-yl)-butyl]-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-{4-[4-(5-chloro-2-methoxy-phenyl)-piperazin-1-yl]-butyl}-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-{4-[4-(3,4-dimethoxy-phenyl)-piperazin-1-yl]-butyl}-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-[4-(4-benzo[1,2,5]thiadiazol-5-yl-piperazin-1-yl)-butyl]-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-{4-[4-(1H-indol-5-yl)-piperazin-1-yl]-butyl}-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-{4-[4-(4-cyano-3-methoxy-phenyl)-piperazin-1-yl]-butyl}-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 3-{4-[4-(2,3-dihydro-benzofuran-5-yl)-piperazin-1-yl]-butyl}-1H-indole-5-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 2-{4-[4-(5-cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile (276863-95-7) → 4-{4-[4-(5-cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h 2: K2CO3; KI / dimethylformamide / Heating View Scheme

Upstream product

• 15861-24-2 1H-indole-5-carbonitrile 
• 4635-59-0 4-Chlorobutanoyl chloride 
• 1670-87-7 SD-169 

Downstream Products

• 143612-79-7 3-(4-chlorobutyl)-5-cyanoindole 
• 1398358-62-7 3-(4-chlorobutanoyl)-1-tosyl-1H-indole-5-carbonitrile 
• 914927-40-5 3-(4-hydroxybutyl)-1H-indole-5-carbonitrile 
• 1451194-34-5 3-(4-chloro-1-hydroxy-butyl)-1H-indol-5-carbonitrile 
• 816438-46-7 3-(4-chloro-butyl)-2,3-dihydro-1H-indole-5-carbonitrile 
• 163521-11-7 5-(4-[4-(5-cyano-3-indolyl)butyl]-1-piperazinyl)benzofuran-2-carboxylic acid ethyl ester 
• 163521-19-5 5-{4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl}benzofuran-2-carboxylic acid 
• 143612-66-2 3-[4-(4-p-methoxyphenylpiperazino)butyl]-5-cyanoindole 

Relevant articles and documents

Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment

Depression, a severe mental disease, is greatly difficult to treat and easy to induce other neuropsychiatric symptoms, the most frequent one is cognitive impairment. In this study, a series of novel vilazodone-tacrine hybrids were designed, synthesized and evaluated as multitarget agents against depression with cognitive impairment. Most compounds exhibited good multitarget activities and appropriate blood-brain barrier permeability. Specifically, compounds 1d and 2a exhibited excellent 5-HT1A agonist activities (1d, EC50 = 0.36 ± 0.08 nM; 2a, EC50 = 0.58 ± 0.14 nM) and 5-HT reuptake inhibitory activities (1d, IC50 = 20.42 ± 6.60 nM; 2a, IC50 = 22.10 ± 5.80 nM). In addition, they showed moderate ChE inhibitory activities (1d, AChE IC50 = 1.72 ± 0.217 μM, BuChE IC50 = 0.34 ± 0.03 μM; 2a, AChE IC50 = 2.36 ± 0.34 μM, BuChE IC50 = 0.10 ± 0.01 μM). Good multitarget activities with goodt blood-brain barrier permeability of 1d and 2a make them good lead compounds for the further study of depression with cognitive impairment.

Substituted indole compounds, as well as using method and application thereof

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