143612-79-7

Basic information

• Product Name: 3-(4-Chlorbutyl)-1H-indol-5-carbonitril
• Synonyms: 3-(4-Chlorbutyl)-1H-indol-5-carbonitril;3-(4-Chlorobutyl)indole-5-carbonitrile;Vilazodone interMediate;1H-Indole-5-carbonitrile, 3-(4-chlorobutyl)-;InterMediate of Vilazodone;3-(4-Chlorbutyl)-1H-indol-5-carbonitrile;3-(4-chloro-butyl)-5-cyanoindole;3-(4- chlorideDing Ji)-5- cyanoindole
• CAS NO: 143612-79-7
• Molecular Formula: C₁₃H₁₃ClN₂
• Molecular Weight: 232.70872
• EINECS: 1308068-626-2
• Product Categories: Intermediates;Aromatics;Heterocycles;Inhibitors
• Mol File: 143612-79-7.mol
• Article Data: 26

Chemical Properties

• Melting Point: 99-100℃
• Boiling Point: 448.1±35.0 °C(Predicted)
• Appearance: /
• Density: 1.22
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Slightly, Ethyl Acetate (Slightly)
• PKA: 15.93±0.30(Predicted)
• CAS DataBase Reference: 3-(4-Chlorbutyl)-1H-indol-5-carbonitril(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(4-Chlorbutyl)-1H-indol-5-carbonitril(143612-79-7)
• EPA Substance Registry System: 3-(4-Chlorbutyl)-1H-indol-5-carbonitril(143612-79-7)

Safety Data

• Hazardous Substances Data: 143612-79-7(Hazardous Substances Data)

Usage

Uses

Reactant in the preparation of allosteric IGF-1R inhibitors, and dual 5-HT1A receptor agonists and serotonin reuptake inhibitors.

InChI:InChI=1S/C13H13ClN2/c14-6-2-1-3-11-9-16-13-5-4-10(8-15)7-12(11)13/h4-5,7,9,16H,1-3,6H2

Synthetic route

1-dimethylamino-2-(2-nitro-5-cyano)phenyl-6-chloro-n-hex-1-ene → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 50 - 55℃; under 1500.15 - 2250.23 Torr; for 5h; Autoclave;	95.5%

1-methoxy-2-(2-nitro-5-cyano)phenyl-6-chloro-n-hex-1-ene → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 50 - 55℃; under 1500.15 - 2250.23 Torr; for 5h; Reagent/catalyst; Autoclave;	92.1%

4-cyanophenyldiazonium tetrafluoroborate (2252-32-6) + 6-chlorohexylzinc bromide (135579-83-8) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
With formic acid In toluene at -44 - 120℃; under 228.015 Torr; for 1.33333h; Temperature; Solvent; Reagent/catalyst; Inert atmosphere;	89%

4-chlorobutyl bromide (6940-78-9) + 1H-indole-5-carbonitrile (15861-24-2) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
With zinc(II) chloride In dichloromethane at -10 - 5℃; for 2h; Temperature;	88%

1-(2-nitro-5-cyano)phenyl-5-chloro-n-pentane + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Stage #1: 1-(2-nitro-5-cyano)phenyl-5-chloro-n-pentane; N,N-dimethyl-formamide dimethyl acetal With copper(l) chloride In N,N-dimethyl-formamide at 95 - 100℃; for 5h; Stage #2: With palladium 10% on activated carbon; hydrogen In methanol; N,N-dimethyl-formamide at 50 - 55℃; under 1500.15 - 2250.23 Torr; for 5h; Autoclave;	87.7%

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%

1-(2-nitro-5-cyano)phenyl-5-chloro-n-pentane + trimethyl orthoformate (149-73-5) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Stage #1: 1-(2-nitro-5-cyano)phenyl-5-chloro-n-pentane; trimethyl orthoformate With zinc(II) chloride In N,N-dimethyl-formamide at 100 - 105℃; for 5h; Stage #2: With palladium 10% on activated carbon; hydrogen In methanol; N,N-dimethyl-formamide at 50 - 55℃; under 1500.15 - 2250.23 Torr; for 5h; Autoclave;	86.9%

6-chlorohexanal-4-cyanophenylhydrazone → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
With phosphoric acid In water; toluene for 3h; Solvent; Time; Fischer Indole Synthesis; Reflux;	74%
With polyphosphoric acid In acetonitrile for 1h; Reflux;	60%

1-p-toluenesulfonyl-3-(4-chlorobutyl)-5-cyanoindole (1398358-69-4) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
With sodium hydride In N,N-dimethyl acetamide at 60℃; for 5h; Inert atmosphere;	65%

1H-indole-5-carbonitrile (15861-24-2) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 73 percent / isobutyl-AlCl2 / CH2Cl2 / 15 - 30 °C 2: 26 percent / sodium bis(2-methoxyethoxy)aluminum hydride / tetrahydrofuran; toluene / 2 h View Scheme
Multi-step reaction with 2 steps 1: isobutylaluminum dichloride / dichloromethane 2: sodium bis(2-methoxyethoxy)aluminium dihydride / tetrahydrofuran View Scheme
Multi-step reaction with 2 steps 1.1: titanium tetrachloride / dichloromethane / 0.75 h / 0 - 5 °C / Inert atmosphere 1.2: 5 h / 20 °C / Inert atmosphere 2.1: boron trifluoride diethyl etherate; sodium tetrahydroborate / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 1,2-dichloro-ethane 2: sodium tetrahydroborate; boron trifluoride diethyl etherate View Scheme
Multi-step reaction with 2 steps 1.1: titanium tetrachloride / dichloromethane / 0.75 h / 0 - 5 °C / Inert atmosphere 1.2: 5 h / 20 °C 2.1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere View Scheme

6-chlorohexanal (52387-36-7) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / toluene / 2 h / 0 - 20 °C 2: phosphoric acid / 65 - 75 °C View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid / water; methanol / 0.33 h / 20 °C 1.2: 20 °C 2.1: phosphoric acid / toluene / 10.16 h / 20 - 60 °C View Scheme

6-chloro-1-hexanol (2009-83-8) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite; sodium hydrogencarbonate / toluene / 0 °C 2: triethylamine / toluene / 2 h / 0 - 20 °C 3: phosphoric acid / 65 - 75 °C View Scheme
Multi-step reaction with 3 steps 1.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.67 h / -78 °C / Inert atmosphere 1.2: 0.5 h / -78 - 20 °C / Inert atmosphere 2.1: sulfuric acid / water; methanol / 0.33 h / 20 °C 2.2: 20 °C 3.1: phosphoric acid / toluene / 10.16 h / 20 - 60 °C View Scheme
Multi-step reaction with 3 steps 1.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide / dichloromethane / 25 - 30 °C 1.2: 0 - 5 °C 2.1: sulfuric acid / water; N,N-dimethyl acetamide / 1 h / 25 - 35 °C 3.1: phosphoric acid / water; toluene / 3 h / Reflux View Scheme

(Z)-4-(2-(6-chlorohexylidene)hydrazinyl)benzonitrile (1527470-83-2) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
With phosphoric acid at 65 - 75℃;

4-[(2E)-2-(6-chlorohexylidene)hydrazinyl]benzonitrile (1527470-88-7) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
With phosphoric acid In toluene at 20 - 60℃; for 10.16h; Solvent; Temperature;

4-Aminobenzonitrile (873-74-5) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium nitrite; hydrogenchloride / water / -10 °C 1.2: -10 °C 2.1: sulfuric acid / water; N,N-dimethyl acetamide / 1 h / 25 - 35 °C 3.1: phosphoric acid / water; toluene / 3 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: hydrogenchloride / water 1.2: 1 h / 2 °C 2.1: sodium hydrogensulfite / water / 2 h / 85 °C 2.2: 0.5 h / 50 °C 3.1: sulfuric acid / water; ethanol / 4 h / 80 °C View Scheme

6-chlorohexanal (52387-36-7) + 4-hydrazinobenzonitrile hydrochloride (2863-98-1) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid / water; N,N-dimethyl acetamide / 1 h / 25 - 35 °C 2: phosphoric acid / water; toluene / 3 h / Reflux View Scheme
With sulfuric acid In ethanol; water at 80℃; for 4h; Reagent/catalyst; Temperature; Fischer Indole Synthesis;	162 g

4-hydrazinobenzonitrile hydrochloride (2863-98-1) + 1,1-dimethoxy-6-chlorohexane (92886-57-2) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
In methanol; water at 70 - 72℃; for 1h; Temperature; Inert atmosphere;	8 g
In methanol; water at 72℃; for 1h; Concentration; Solvent; Temperature; Inert atmosphere;	9.5 g

SD-169 (1670-87-7) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 3 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 3.1: diborane / dichloromethane / 4 h / 20 °C / Reflux; Large scale View Scheme

3-(4-chlorobut-2-ene-1-yl)-5-cyanoindole → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In tetrahydrofuran at 10 - 15℃; under 1500.15 Torr; for 4h; Pressure; Temperature;	17.2 g

1-bromo-6-chlorohexane (6294-17-3) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: zinc; iodine / N,N-dimethyl acetamide / 5 h / 60 °C / Inert atmosphere 2: formic acid / toluene / 1.33 h / -44 - 120 °C / 228.01 Torr / Inert atmosphere View Scheme

1-(2-nitro-5-cyano)phenyl-5-chloro-n-pentane → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: zinc(II) chloride / N,N-dimethyl-formamide / 4 h / 100 - 105 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 5 h / 50 - 55 °C / 1500.15 - 2250.23 Torr / Autoclave View Scheme

hexahydro-2H-oxepin-2-one (502-44-3) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / dichloromethane 2: formic acid 3: sulfuric acid / water; ethanol / 4 h / 80 °C View Scheme

6-chlorohexanoyl chloride (19347-73-0) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: formic acid 2: sulfuric acid / water; ethanol / 4 h / 80 °C View Scheme

p-cyanobenzenediazonium chloride (25102-85-6) → 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydrogensulfite / water / 2 h / 85 °C 1.2: 0.5 h / 50 °C 2.1: sulfuric acid / water; ethanol / 4 h / 80 °C View Scheme

di-tert-butyl dicarbonate (24424-99-5) + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → tert-butyl 3-(4-chlorobutyl)-5-cyano-1H-indole-1-carboxylate

Conditions	Yield
With triethylamine In dichloromethane at 40 - 45℃; for 24h;	96.5%

3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) + 5-(1-piperazinyl)benzofuran-2-carboxamide (183288-46-2) → vilazodone (163521-12-8)

Conditions	Yield
Stage #1: 3-(4-chlorobutyl)-5-cyanoindole With sodium iodide In N,N-dimethyl-formamide at 25 - 30℃; for 0.25h; Stage #2: 5-(1-piperazinyl)benzofuran-2-carboxamide With tetrabutylammomium bromide; sodium hydrogencarbonate In N,N-dimethyl-formamide at 110 - 115℃; for 1.25h; Reagent/catalyst; Temperature; Time; Solvent;	95.7%
With sodium carbonate In water at 90 - 100℃;	94%
Stage #1: 5-(1-piperazinyl)benzofuran-2-carboxamide With hydrogenchloride In water at 20 - 35℃; pH=6.5 - 7; Stage #2: 3-(4-chlorobutyl)-5-cyanoindole With sodium carbonate In water; isopropyl alcohol at 75 - 85℃; for 12h; Reagent/catalyst; pH-value;	94%

3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) + 5-(1-piperazinyl)benzofuran-2-carboxamide (183288-46-2) → 5-{4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl}-1-benzofuran-2-carboxamide

Conditions	Yield
Stage #1: 3-(4-chlorobutyl)-5-cyanoindole With sodium iodide In N,N-dimethyl-formamide at 25 - 30℃; for 0.25h; Stage #2: 5-(1-piperazinyl)benzofuran-2-carboxamide With tetrabutylammomium bromide; sodium hydrogencarbonate In N,N-dimethyl-formamide at 110 - 115℃; for 1.25h; Temperature; Solvent; Reagent/catalyst;	95.7%

5-(piperazin-1-yl)benzofuran-2-carboxamide hydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → vilazodone hydrochloride

Conditions	Yield
Stage #1: 5-(piperazin-1-yl)benzofuran-2-carboxamide hydrochloride With sodium carbonate; potassium iodide In N,N-dimethyl-formamide at 70℃; Stage #2: 3-(4-chlorobutyl)-5-cyanoindole In N,N-dimethyl-formamide at 80℃; for 12h;	90.2%

6-(2-(piperazin-1-yl)pyrimidin-5-yl)nicotinamide dihydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 6-(2-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)pyrimidin-5-yl)nicotinamide

Conditions	Yield
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	86.4%
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	86.4%

n-butyl 5-(piperazin-1-yl)-1-benzofuran-2-carboxylate hydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → n-butyl 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxylate hydrochloride

Conditions	Yield
Stage #1: n-butyl 5-(piperazin-1-yl)-1-benzofuran-2-carboxylate hydrochloride; 3-(4-chlorobutyl)-5-cyanoindole With tetrabutylammomium bromide; triethylamine In acetone at 55 - 90℃; Stage #2: With hydrogenchloride In isopropyl alcohol at 50℃; pH=2; Reflux;	85%

ethyl 5-(1-piperazinyl)benzofuran-2-carboxylate dihydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-2-benzofurancarboxylic acid ethyl ester hydrochloride (1422956-25-9)

Conditions	Yield
Stage #1: ethyl 5-(1-piperazinyl)benzofuran-2-carboxylate dihydrochloride; 3-(4-chlorobutyl)-5-cyanoindole With tetrabutylammomium bromide; triethylamine at 85 - 90℃; for 10h; Stage #2: With hydrogenchloride In isopropyl alcohol at 50 - 55℃; pH=2; Reflux;	83%
Stage #1: ethyl 5-(1-piperazinyl)benzofuran-2-carboxylate dihydrochloride; 3-(4-chlorobutyl)-5-cyanoindole With potassium iodide In acetonitrile at 20℃; for 0.166667h; Stage #2: With potassium carbonate; triethylamine In acetonitrile at 20 - 80℃; for 20.16h; Reagent/catalyst; Solvent;	48 g

ethyl 5-(1-piperazinyl)benzofuran-2-carboxylate hydrobromide (1469427-45-9) + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-2-benzofurancarboxylic acid ethyl ester hydrochloride (1422956-25-9)

Conditions	Yield
Stage #1: ethyl 5-(1-piperazinyl)benzofuran-2-carboxylate hydrobromide; 3-(4-chlorobutyl)-5-cyanoindole With tetrabutylammomium bromide; triethylamine at 85 - 90℃; for 10h; Stage #2: With hydrogenchloride In isopropyl alcohol at 50 - 55℃; pH=2; Reflux;	83%

ethyl 5-(1-piperazinyl)benzofuran-2-carboxylate dihydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)benzofuran-2-carboxylate hydrochloride

Conditions	Yield
Stage #1: ethyl 5-(1-piperazinyl)benzofuran-2-carboxylate dihydrochloride; 3-(4-chlorobutyl)-5-cyanoindole With tetrabutylammomium bromide; triethylamine at 85 - 90℃; for 10h; Stage #2: With hydrogenchloride In isopropyl alcohol; acetone at 50℃; pH=2; Reflux;	83%

ethyl 5-(1-piperazinyl)benzofuran-2-carboxylate hydrobromide + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → ethyl 5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)benzofuran-2-carboxylate hydrochloride

Conditions	Yield
Stage #1: ethyl 5-(1-piperazinyl)benzofuran-2-carboxylate hydrobromide; 3-(4-chlorobutyl)-5-cyanoindole With tetrabutylammomium bromide; triethylamine at 85 - 90℃; for 10h; Stage #2: With hydrogenchloride In isopropyl alcohol; acetone at 50℃; pH=2; Reflux;	83%

5-piperazin-1-ylbenzofuran-2-carboxamide hydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → vilazodone (163521-12-8)

Conditions	Yield
With potassium hydrogencarbonate; sodium iodide In N,N-dimethyl-formamide at 95 - 105℃; for 20h;	83%

2-chloropyrimidine (1722-12-9) + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 3-(4-chlorobutyl)-1-(pyrimidin-2-yl)-1H-indole-5-carbonitrile

Conditions	Yield
Stage #1: 3-(4-chlorobutyl)-5-cyanoindole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: 2-chloropyrimidine In N,N-dimethyl-formamide; mineral oil at 130℃; for 24h;	83%

4-methyl-2-(2-(piperazin-1-yl)pyrimidin-5-yl)thiazole-5-carboxamide dihydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 2-(2-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)pyrimidin-5-yl)-4-methylthiazole-5-carboxamide

Conditions	Yield
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	78.8%
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	78.8%

4-methyl-2-(2-(piperazin-1-yl)pyrimidin-5-yl)thiazole-5-carboxylic acid ethyl ester dihydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 2-(2-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)pyrimidin-5-yl)-4-methylthiazole-5-carboxylic acid ethyl ester

Conditions	Yield
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	75.6%
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	75.6%

4-methyl-2-(2-(piperazin-1-yl)pyrimidin-5-yl)oxazole-5-carboxylic acid ethyl ester dihydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 2-(2-(4-(4-(5-Cyano-1H-indol-3-yl)butyl)piperazin-1-yl)pyrimidin-5-yl)-4-methyloxazole-5-carboxylic acid ethyl ester

Conditions	Yield
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	75.1%
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	75.1%

4-methyl-2-(2-(piperazin-1-yl)pyrimidin-5-yl)oxazole-5-carboxamide dihydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 2-(2-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)pyrimidin-5-yl)-4-methyloxazole-5-carboxamide

Conditions	Yield
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	73.6%
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	73.6%

5-(2-(piperazin-1-yl)pyrimidin-5-yl)pyridine-2-carboxamide dihydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 5-(2-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)pyrimidin-5-yl)pyridine-2-carboxamide

Conditions	Yield
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	73.6%
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	73.6%

5-(2-(piperazin-1-yl)pyrimidin-5-yl)pyridine-2-carboxamide dihydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 6-(2-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)pyrimidin-5-yl)pyridine-2-carboxamide

Conditions	Yield
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 36h;	72.6%

6-(2-(piperazin-1-yl)pyrimidin-5-yl)pyridine-2-carboxamide dihydrochloride + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 6-(2-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)pyrimidin-5-yl)pyridine-2-carboxamide

Conditions	Yield
With sodium carbonate; sodium iodide In acetonitrile at 90℃; for 6h;	72.6%

n-propyl 5-(piperazin-1-yl)benzofuran-2-carboxylate + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → vilazodone (163521-12-8)

Conditions	Yield
Stage #1: n-propyl 5-(piperazin-1-yl)benzofuran-2-carboxylate; 3-(4-chlorobutyl)-5-cyanoindole With tetrabutylammomium bromide; potassium carbonate; potassium iodide In acetonitrile Reflux; Stage #2: With ammonium hydroxide In acetonitrile at 25 - 30℃; for 72h;	72%

4-piperazinylquinoline (118306-89-1) + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → 3-(4-(4-(quinolin-4-yl)piperazin-1-yl)butyl)-1H-indole-5-carbonitrile

Conditions	Yield
With triethylamine; potassium iodide In acetonitrile for 24h; Reflux;	72%

methyl 5-(piperazin-1-yl)-1-benzofuran-2-carboxylate hydrochloride (1451194-32-3) + 3-(4-chlorobutyl)-5-cyanoindole (143612-79-7) → methyl 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxylate hydrochloride

Conditions	Yield
Stage #1: methyl 5-(piperazin-1-yl)-1-benzofuran-2-carboxylate hydrochloride; 3-(4-chlorobutyl)-5-cyanoindole With tetrabutylammomium bromide; triethylamine In acetone at 55 - 90℃; Stage #2: With hydrogenchloride In isopropyl alcohol at 50℃; pH=2; Reflux;	70%

Upstream product

• 34067-76-0 6-hydroxyhexanal 
• 1398358-69-4 1-p-toluenesulfonyl-3-(4-chlorobutyl)-5-cyanoindole 
• 6940-78-9 4-chlorobutyl bromide 
• 15861-24-2 1H-indole-5-carbonitrile 
• 25102-85-6 p-cyanobenzenediazonium chloride 
• 19347-73-0 6-chlorohexanoyl chloride 
• 502-44-3 hexahydro-2H-oxepin-2-one 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 149-73-5 trimethyl orthoformate 
• 2252-32-6 4-cyanophenyldiazonium tetrafluoroborate 
• 135579-83-8 6-chlorohexylzinc bromide 
• 6294-17-3 1-bromo-6-chlorohexane 
• 1670-87-7 SD-169 
• 2863-98-1 4-hydrazinobenzonitrile hydrochloride 

Downstream Products

• 143612-66-2 3-[4-(4-p-methoxyphenylpiperazino)butyl]-5-cyanoindole 
• 163521-12-8 vilazodone 
• 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 

Relevant articles and documents

Practical and Scalable Manufacturing Process for a Novel Dual-Acting Serotonergic Antidepressant Vilazodone

Vilazodone combines the effects of a selective serotonin reuptake inhibitor with the 5-HT1A receptor partial agonist activity. Here, we report the development of a viable and scalable process for manufacturing vilazodone that features a convergent synthetic approach, with low cost and high purity. The key indole synthesis was improved to first make up the hydrazone intermediate and then modify a pendant hydroxy group to realize a much increased overall yield. This process was successfully used to prepare >2 kg of vilazodone hydrochloride with a total yield of 56.2% and purity of 99.93%.

Alternative approach to synthesis of 3-(4-Chloro butyl)- 1H -indole-5-carbonitrile: A key intermediate of vilazodone hydrochloride, an antidepressant drug

An alternative and efficient telescopic approach to the synthesis of 3-(4-chloro butyl)-1H-indole -5-carbonitrile (2), a key intermediate in the synthesis of vilazodone hydrochloride (1), is described.

Preparation method of vilazodone intermediate

The invention relates to a preparation method of a vilazodone intermediate, which comprises the following steps: carrying out F-C alkylation reaction on a compound 1 raw material and 1-bromo-4-chlorobutane under the action of anhydrous zinc chloride, and carrying out one-step reaction to obtain a compound I, namely, the vilazodone intermediate. Compared with the prior art, the method has the advantages of short reaction route, easiness in post-treatment, high yield, cheap and easily available reagents used in the F-C reaction, convenience in operation, simplicity in post-treatment, low cost, small environmental pollution and suitability for industrial production of the vilazodone intermediate I.

Production process 3-(4-chlorobutyl) indole -5- carbonitrile (by machine translation)

The invention discloses 3 - (4 -chlorobutyl) indo- 5 5-carbonitrile production process, which comprises the following steps, adding :chlorobutyl chloride in a clean reactor: stirring and cooling, with nitrogen in the same reactor at, temperature, and stirring the mixture in a reactor, for one time, to complete dissolution in a solvent, and stirring and cooling by 5 °C, steps: Stirring of 4 - Cooling The reactor, with nitrogen gas in the same reactor at a temperature of about 5-10 °C DEG . The production process of the invention is simple and reliable, production cost, of a reactor in the same reactor is stirred and uniformly: DEG C 5 - and the product purity, is, more suitable for industrialized, large-scale preparation, of the same reactor, and the production process, conditions, are more suitable for industrialized mass preparation of the product in, the same reactor, respectively . (by machine translation)