5118-13-8

Basic information

• Product Name: 4-BROMO-BENZO[B]THIOPHENE
• Synonyms: 4-BROMO-BENZO[B]THIOPHENE;4-Bromobenzothiophene;4-BROMO-1-BENZOTHIOPHENE;Benzo[b]thiophene,4-broMo-;4-Bromo-1-benzothiophene, 4-Bromothianaphthene;4-Bromothianaphthene;5-cyanobenzothiophene;4-bromo-thiophene
• CAS NO: 5118-13-8
• Molecular Formula: C₈H₅BrS
• Molecular Weight: 213.0943
• EINECS: 1592732-453-0
• Product Categories: Benzothiophene;Halogenated;Organohalides
• Mol File: 5118-13-8.mol
• Article Data: 23

Chemical Properties

• Boiling Point: 284.713 °C at 760 mmHg
• Flash Point: 125.99 °C
• Appearance: /
• Density: 1.649 g/cm³
• Vapor Pressure: 0.005mmHg at 25°C
• Refractive Index: 1.704
• Storage Temp.: 2-8°C(protect from light)
• CAS DataBase Reference: 4-BROMO-BENZO[B]THIOPHENE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-BROMO-BENZO[B]THIOPHENE(5118-13-8)
• EPA Substance Registry System: 4-BROMO-BENZO[B]THIOPHENE(5118-13-8)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 5118-13-8(Hazardous Substances Data)

Usage

Synthesis

The traditional synthesis method is to take 2-bromo-6-fluorobenzaldehyde as a raw material, cyclize the raw material with mercaptoacetic acid in a DMF solvent to obtain 4-chlorobenzo [b] thiophene-2-carboxylic acid, and then decarboxylate the product at a high temperature in a quinoline/copper powder system to obtain the 4-chlorobenzo [b] thiophene.

Uses

4-bromobenzo [b] thiophene is an important intermediate in the drug ipiprazole for the treatment of schizophrenia.

InChI:InChI=1/C8H5BrS/c9-7-2-1-3-8-6(7)4-5-10-8/h1-5H

Synthetic route

Benzo[b]thiophene (95-15-8) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Stage #1: Benzo[b]thiophene With dihydrogen peroxide; acetic acid at 78℃; for 0.5h; Inert atmosphere; Stage #2: With tetrabutylammomium bromide; sodium bromide In water at 120℃; under 7220.48 Torr; for 20h;	98.8%

4-bromo-benzo[b]thiophene-2-carboxylic acid (5194-37-6) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
With acetic acid; silver carbonate In dimethyl sulfoxide at 120℃; Further stages;	95%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl acetamide at 200℃; for 1h; microwave irradiation;	91%
With triethylenediamine at 120 - 180℃; for 6h;	91.7%

4,7-dibromobenzo[b]thiophene (1391908-40-9) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Stage #1: 4,7-dibromobenzo[b]thiophene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: With methanol In tetrahydrofuran; hexane at -78℃;	53%

1-bromo-3-[(2,2-dimethoxyethyl)sulfanyl]benzene (19296-69-6) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
In chlorobenzene	14%

benzo[B]thiophen-4-ylamine (17402-83-4) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
With hydrogen bromide; sodium nitrite Behandeln der Reaktionsloesung mit Kupfer(I)-bromid;

4-bromo-5-aminobenzothiophene (4965-27-9) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
With sulfuric acid; sodium nitrite Behandeln des Diazoniumsalzes mit wss. Hypophosphorigsaeure ;

1-bromo-3-(2,2-diethoxy-ethylsulfanyl)benzene (17347-29-4) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Stage #1: 1-bromo-3-(2,2-diethoxy-ethylsulfanyl)benzene With PPA In chlorobenzene at 130℃; for 1h; Stage #2: With sodium hydroxide In water; chlorobenzene at 20℃;

4-nitrobenzene[b]thiophene (10133-34-3) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium/charcoal; ethanol / Hydrogenation 2: aqueous hydrobromic acid; sodium nitrite / Behandeln der Reaktionsloesung mit Kupfer(I)-bromid View Scheme

benzo[b]thiophen-5-yl-acetamide (18044-91-2) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: nitric acid 2: aq.-ethanolic NaOH-solution 3: aqueous sulfuric acid; sodium nitrite / Behandeln der Reaktionsloesung mit wss. Hypophosphorigsaeure 4: palladium/charcoal; ethanol / Hydrogenation 5: aqueous hydrobromic acid; sodium nitrite / Behandeln der Reaktionsloesung mit Kupfer(I)-bromid View Scheme

4-nitro-benzo[b]thiophen-5-ylamine (127491-04-7) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: aqueous sulfuric acid; sodium nitrite / Behandeln der Reaktionsloesung mit wss. Hypophosphorigsaeure 2: palladium/charcoal; ethanol / Hydrogenation 3: aqueous hydrobromic acid; sodium nitrite / Behandeln der Reaktionsloesung mit Kupfer(I)-bromid View Scheme

N-(4-nitro-benzo[b]thiophen-5-yl)-acetamide (857473-95-1) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: aq.-ethanolic NaOH-solution 2: aqueous sulfuric acid; sodium nitrite / Behandeln der Reaktionsloesung mit wss. Hypophosphorigsaeure 3: palladium/charcoal; ethanol / Hydrogenation 4: aqueous hydrobromic acid; sodium nitrite / Behandeln der Reaktionsloesung mit Kupfer(I)-bromid View Scheme

3-Bromothiophenol (6320-01-0) + Bromoacetaldehyde diethyl acetal (2032-35-1) → 6-bromobenzothiophene (17347-32-9) + 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Stage #1: 3-Bromothiophenol; Bromoacetaldehyde diethyl acetal With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 24h; Stage #2: With PPA In 1,2-dichloro-ethane for 1h; Heating / reflux;

1-bromo-3-[(2,2-dimethoxyethyl)sulfanyl]benzene (19296-69-6) → 6-bromobenzothiophene (17347-32-9) + 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
With poliphosphoric acid In chlorobenzene for 2h; Product distribution / selectivity; Heating / reflux;
With PPA at 130℃; for 4.5 - 5.5h; Heating / reflux;
With PPA In chlorobenzene at 130℃; for 4.5 - 5.5h; Heating / reflux;
With PPA In chlorobenzene at 140℃; for 5.5h; Heating / reflux;
With phenylpropanol amine In chlorobenzene for 12h; Reflux; Overall yield = 91 %; Overall yield = 7 g;

1-bromo-3-(2,2-diethoxy-ethylsulfanyl)benzene (17347-29-4) → 6-bromobenzothiophene (17347-32-9) + 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
With PPA In 1,2-dichloro-ethane for 1h; Heating / reflux;
With sodium carbonate In dichloromethane for 4h; Reflux; Overall yield = 58 %; Overall yield = 0.33 g;

3,6-dibromo-2-fluorobenzaldehyde (870703-68-7) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C / Inert atmosphere 1.2: 7 h / -30 °C / Inert atmosphere 2.1: potassium carbonate / methanol / 2 h / 0 - 20 °C / Inert atmosphere 3.1: gold(I) chloride / 1,4-dioxane; water / 0.17 h / 20 °C / Inert atmosphere 4.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 °C 4.2: -78 °C View Scheme

3,6-dibromo-2-(t-butylsulfanyl)(ethynyl)benzene (1391908-38-5) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: gold(I) chloride / 1,4-dioxane; water / 0.17 h / 20 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 °C 2.2: -78 °C View Scheme

3,6-dibromo-2-(t-butylsulfanyl)benzaldehyde (1391908-37-4) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium carbonate / methanol / 2 h / 0 - 20 °C / Inert atmosphere 2.1: gold(I) chloride / 1,4-dioxane; water / 0.17 h / 20 °C / Inert atmosphere 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 °C 3.2: -78 °C View Scheme

3-Bromothiophenol (6320-01-0) → 6-bromobenzothiophene (17347-32-9) + 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 - 20 °C 1.2: 2 h / 20 °C 2.1: phenylpropanol amine / chlorobenzene / 12 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 16 h / 20 °C 2: sodium carbonate / dichloromethane / 4 h / Reflux View Scheme

3-Bromothiophenol (6320-01-0) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide / dimethyl sulfoxide; water 2: chlorobenzene View Scheme
Multi-step reaction with 2 steps 1.1: potassium hydroxide / water; dimethyl sulfoxide / 120 h / 20 °C 2.1: PPA / chlorobenzene / 1 h / 130 °C 2.2: 20 °C View Scheme

2,6-dibromobenzaldehyde (67713-23-9) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 2 steps 2: copper View Scheme

3-fluorobromobenzene (1073-06-9) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-butyllithium; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 1.5 h / -78 °C / Inert atmosphere 1.2: 0.33 h / -78 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 60 °C / Inert atmosphere 3.1: sodium hydroxide / water; tetrahydrofuran / 1 h / 70 °C 4.1: silver carbonate; acetic acid / dimethyl sulfoxide / 120 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium; N-ethyl-N,N-diisopropylamine / tetrahydrofuran; hexane / 1 h / -78 °C / Inert atmosphere 1.2: 0.5 h / 20 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 60 °C / Inert atmosphere 3.1: sodium hydroxide / water; tetrahydrofuran / 1 h / 70 °C 4.1: silver carbonate; acetic acid / dimethyl sulfoxide / 120 °C View Scheme

2-bromo-6-fluorobenzaldehyde (360575-28-6) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 60 °C / Inert atmosphere 2: sodium hydroxide / water; tetrahydrofuran / 1 h / 70 °C 3: silver carbonate; acetic acid / dimethyl sulfoxide / 120 °C View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 4 h / 30 - 35 °C 2: toluene / 4 h / 110 °C 3: sodium hydride / tetrahydrofuran / 2 h / 20 - 30 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide / N,N-dimethyl-formamide / 2 h / 10 - 15 °C 2: toluene / 4 h / 110 °C 3: sodium hydride / tetrahydrofuran / 2 h / 20 - 30 °C / Inert atmosphere View Scheme

4-bromobenzo[b]thiophene-2-carboxylic acid ethyl ester (93103-82-3) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water; tetrahydrofuran / 1 h / 70 °C 2: silver carbonate; acetic acid / dimethyl sulfoxide / 120 °C View Scheme

C8H6BrClOS → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 4 h / 110 °C 2: sodium hydride / tetrahydrofuran / 2 h / 20 - 30 °C / Inert atmosphere View Scheme

C26H21BrOPS(1+)*Cl(1-) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20 - 30℃; for 2h; Solvent; Wittig Olefination; Inert atmosphere;

5-bromobenzo[b]thiophene (4923-87-9) → 4-bromobenzo[b]thiophene (5118-13-8)

Conditions	Yield
With phosphazene base-P4-tert-butyl In 1,4-dioxane at 80℃; for 21h;	6 %Spectr.

piperazine (110-85-0) + 4-bromobenzo[b]thiophene (5118-13-8) → 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride

Conditions	Yield
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline In toluene at 100℃; for 24h; Solvent; Reagent/catalyst; Inert atmosphere;	97.2%

4-bromobenzo[b]thiophene (5118-13-8) + chloro-trimethyl-silane (75-77-4) → 7-bromo-2-trimethylsilyl-benzothiophene (324769-04-2)

Conditions	Yield
Stage #1: 4-bromobenzo[b]thiophene; chloro-trimethyl-silane With lithium diisopropyl amide In tetrahydrofuran; n-heptane at -70℃; for 1.53333h; Stage #2: With hydrogenchloride In tetrahydrofuran; n-heptane at -70℃; for 1.5h;	95%

4-bromobenzo[b]thiophene (5118-13-8) + 4-tolyl iodide (624-31-7) → 4-bromo-2-(p-tolyl)benzo[b]thiophene

Conditions	Yield
With 1,1,1,3',3',3'-hexafluoro-propanol; sodium acetate; palladium diacetate; silver(l) oxide at 30℃; for 16h; regioselective reaction;	86%

methanol (67-56-1) + 4-bromobenzo[b]thiophene (5118-13-8) + carbon monoxide (201230-82-2) → methyl benzothiophen-4-carboxylate (100590-43-0)

Conditions	Yield
With triethylamine; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate In dimethyl sulfoxide at 80℃; for 24h;	84%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine at 120℃; Inert atmosphere;	44%

piperazine (110-85-0) + 4-bromobenzo[b]thiophene (5118-13-8) → 1-benzo[b]thiophen-4-ylpiperazine hydrochloride

Conditions	Yield
With copper(l) iodide; potassium carbonate; L-proline In N,N-dimethyl-formamide at 110℃; for 10h; Reagent/catalyst; Solvent; Inert atmosphere;	80.54%
With sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium(0); (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl In toluene for 1h; Heating / reflux;
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate

4-bromobenzo[b]thiophene (5118-13-8) + N-thiocyanatodibenzenesulfonimide → 4-bromo-3-thiocyanatobenzo[b]thiophene

Conditions	Yield
With trifluorormethanesulfonic acid In acetonitrile at 60℃; for 12h;	80%

piperazine (110-85-0) + 4-bromobenzo[b]thiophene (5118-13-8) → 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride

Conditions	Yield
Stage #1: piperazine; 4-bromobenzo[b]thiophene With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene for 1h; Reflux; Inert atmosphere; Stage #2: With hydrogenchloride In methanol	79.79%

4-bromobenzo[b]thiophene (5118-13-8) + 7-(4-(piperazin-1-yl)butoxy)quinolin-2(1H)-one → Brexpiprazole (913611-97-9)

Conditions	Yield
Stage #1: 7-[4-(piperazin-1-yl)butoxy]-2(1H)-quinolinone With trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II) In dichloromethane; dimethyl sulfoxide at 25 - 35℃; for 0.25h; Inert atmosphere; Stage #2: 4-bromobenzo[b]thiophene In dichloromethane; dimethyl sulfoxide at 140 - 150℃;	77.8%
With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In 1,4-dioxane at 25 - 115℃; for 15h; Temperature; Inert atmosphere;	40 g

4-bromobenzo[b]thiophene (5118-13-8) + 2-methyl-1-(trimethylsilyloxy)-1-propene (6651-34-9) → 2-(benzo[b]thiophen-4-yl)-2-methylpropanal

Conditions	Yield
With zinc(II) fluoride; tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0) In N,N-dimethyl-formamide; toluene at 85℃; for 18h; Sealed tube; Inert atmosphere;	75%

4-bromobenzo[b]thiophene (5118-13-8) + carbon dioxide (124-38-9) → benzothiophen-4-carboxic acid (10134-95-9)

Conditions	Yield
Stage #1: 4-bromobenzo[b]thiophene With iodine; magnesium In tetrahydrofuran at 50 - 55℃; for 1.5h; Stage #2: carbon dioxide In tetrahydrofuran at 23℃; for 0.25 - 0.333333h; Stage #3: With hydrogenchloride; water In tetrahydrofuran at 0℃;	74%
With manganese; 2.9-dimethyl-1,10-phenanthroline; lithium acetate; cobalt(II) bromide In N,N-dimethyl acetamide at 20℃; under 760.051 Torr; for 12h; Inert atmosphere; Schlenk technique;	62%

4-bromobenzo[b]thiophene (5118-13-8) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → benzo[b]thiophene-4-carbonitrile (17347-34-1)

Conditions	Yield
With [2,2]bipyridinyl; aluminum (III) chloride; nickel(II) acetylacetonate; zinc(II) oxide In 1,2-dimethoxyethane at 145℃; for 12h;	72%

4-bromobenzo[b]thiophene (5118-13-8) + (3‑methylbenzyl)(4‑methylphenyl) sulfide (887078-94-6) → 4-bromo-2-(4-methyl-2-(p-tolylthiomethyl)phenyl)benzo[b]thiophene

Conditions	Yield
With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; silver(l) oxide; Trimethylacetic acid In dichloromethane at 100℃; for 24h; Inert atmosphere; Schlenk technique;	72%

4-bromobenzo[b]thiophene (5118-13-8) + methyl iodide (74-88-4) → 4-bromo-2-methylbenzo[b]thiophene

Conditions	Yield
Stage #1: 4-bromobenzo[b]thiophene With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Stage #2: methyl iodide In tetrahydrofuran at -78℃; for 1h;	71%

4-bromobenzo[b]thiophene (5118-13-8) + ethyl 2-cyanoacetate (105-56-6) → (benzo[b]thien-4-yl)acetonitrile

Conditions	Yield
Stage #1: 4-bromobenzo[b]thiophene; ethyl 2-cyanoacetate With potassium phosphate; N-(2-methylnaphthalen-1-yl)-N’-(pyridin-2-ylmethyl)oxalamide; copper(l) chloride In ethanol at 80℃; for 24h; Schlenk technique; Inert atmosphere; Stage #2: With water In ethanol at 80℃; Schlenk technique; Inert atmosphere; Cooling;	71%

4-bromobenzo[b]thiophene (5118-13-8) → 4-bromo-3-iodobenzo[b]thiophene (1376607-97-4)

Conditions	Yield
With iodine In nitromethane at 120℃; for 1h; Sealed tube; regioselective reaction;	69%

4-bromobenzo[b]thiophene (5118-13-8) + bis(pinacol)diborane (73183-34-3) → 2-(benzo[b]thiophen-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In diethylene glycol dimethyl ether at 80℃; Inert atmosphere; Sealed tube;	60%

4-bromobenzo[b]thiophene (5118-13-8) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → 1-benzo[b]thiophen-4-ylpiperazine hydrochloride

Conditions	Yield
With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate In N,N-dimethyl-formamide at 110℃; for 14h; Reagent/catalyst; Solvent; Inert atmosphere;	55.37%

4-bromobenzo[b]thiophene (5118-13-8) → benzo[b]thiophen-4-ylboronic acid (177735-30-7)

Conditions	Yield
With n-butyllithium; Triisopropyl borate In tetrahydrofuran at -78℃;	49%

4-bromobenzo[b]thiophene (5118-13-8) + acrylic acid methyl ester (292638-85-8) → C12H10O2S

Conditions	Yield
With tetrabutyl-ammonium chloride; palladium diacetate; potassium carbonate In N,N-dimethyl-formamide at 100℃; Inert atmosphere;	49%

6-bromobenzothiophene (17347-32-9) + 4-bromobenzo[b]thiophene (5118-13-8) + dicyanozinc (557-21-1) → benzo[b]thiophene-6-carbonitrile (154650-81-4) + benzo[b]thiophene-4-carbonitrile (17347-34-1)

Conditions	Yield
tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 90 - 100℃; for 3h;	A 46.2% B 23%
tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 90 - 100℃; for 3h;	A 46.2% B 23%

4-bromobenzo[b]thiophene (5118-13-8) + N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3) → 1-(tert-butoxycarbonyl)-4-hydroxy-4-(benzothien-4-yl)piperidine (324769-47-3)

Conditions	Yield
Stage #1: 4-bromobenzo[b]thiophene With magnesium In tetrahydrofuran at 60℃; for 0.0833333h; Inert atmosphere; Stage #2: N-tert-butyloxycarbonylpiperidin-4-one In tetrahydrofuran at 20℃; for 1h; Further stages;	44%

4-bromobenzo[b]thiophene (5118-13-8) + (2-oxo-2-phenylethyl)triphenylphosphonium trifluoroacetate (55161-38-1) → (8,11-dibromobenzo[de]benzo[4,5]thieno[3,2-b]benzo[4,5]thieno[2,3-g]chromen-10-yl)triphenylphosphonium trifluoroacetate

Conditions	Yield
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; cesium acetate; silver(l) oxide In 2,2,2-trifluoroethanol at 120℃; for 24h; Schlenk technique; Inert atmosphere;	42%

6-bromobenzothiophene (17347-32-9) + 4-bromobenzo[b]thiophene (5118-13-8) + copper(I) cyanide (544-92-3) → benzo[b]thiophene-6-carbonitrile (154650-81-4) + benzo[b]thiophene-4-carbonitrile (17347-34-1)

Conditions	Yield
With pyridine In N,N-dimethyl-formamide for 20h; Product distribution / selectivity; Heating / reflux;	A 41% B 39%

4-bromobenzo[b]thiophene (5118-13-8) + benzimidic acid ethyl ester (825-60-5) → 2-(4-bromobenzo[b]thiophen-2-yl)benzonitrile

Conditions	Yield
With tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; potassium acetate; silver fluoride In tert-butyl alcohol at 100℃; for 24h; Schlenk technique;	37%

4-bromobenzo[b]thiophene (5118-13-8) + acrylic acid methyl ester (292638-85-8) → methyl (2a,7b)-cis-7-bromo-1,2,2a,7b-tetrahydrobenzo[b]cyclobuta[d]thiophene-1-carboxylate

Conditions	Yield
With [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate In water; acetonitrile at 50℃; for 24h; Schlenk technique; Inert atmosphere; Irradiation; diastereoselective reaction;	35%

4-bromobenzo[b]thiophene (5118-13-8) + 3-chloro-4-fluorophenylamine (367-21-5) + molybdenum hexacarbonyl (13939-06-5, 199620-15-0) → N-(3-chloro-4-fluorophenyl)benzo[b]thiophene-4-carboxamide

Conditions	Yield
With palladium diacetate; sodium carbonate; tri tert-butylphosphoniumtetrafluoroborate In acetonitrile at 70℃; for 1h; Inert atmosphere; Microwave irradiation;	32%

4-bromobenzo[b]thiophene (5118-13-8) + 2,5-dibromo-terephthalic acid diethyl ester (18013-97-3) + tributyltin chloride (1461-22-9) + tris-(o-tolyl)phosphine (6163-58-2) → diethyl 2,5-di(benzo[b]thiophen-4-yl)terephthalate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0) In tetrahydrofuran; diethyl ether; N,N-dimethyl-formamide	31%

Upstream product

• 4965-27-9 4-bromo-5-aminobenzothiophene 
• 5194-37-6 4-bromo-benzo[b]thiophene-2-carboxylic acid 
• 17347-29-4 1-bromo-3-(2,2-diethoxy-ethylsulfanyl)benzene 
• 6320-01-0 3-Bromothiophenol 
• 19296-69-6 1-bromo-3-[(2,2-dimethoxyethyl)sulfanyl]benzene 
• 4923-87-9 5-bromobenzo[b]thiophene 
• 95-15-8 Benzo[b]thiophene 
• 67713-23-9 2,6-dibromobenzaldehyde 
• 1391908-37-4 3,6-dibromo-2-(t-butylsulfanyl)benzaldehyde 
• 1391908-40-9 4,7-dibromobenzo[b]thiophene 
• 1391908-38-5 3,6-dibromo-2-(t-butylsulfanyl)(ethynyl)benzene 
• 870703-68-7 3,6-dibromo-2-fluorobenzaldehyde 
• 2032-35-1 Bromoacetaldehyde diethyl acetal 
• 857473-95-1 N-(4-nitro-benzo[b]thiophen-5-yl)-acetamide 

Downstream Products

• 88341-06-4 4-acetylbenzothiophen 
• 154650-81-4 benzo[b]thiophene-6-carbonitrile 
• 17347-34-1 benzo[b]thiophene-4-carbonitrile 
• 1191901-07-1 tert-butyl 4-(benzo[b]thiophen-4-yl)piperazine-1-carboxylate 
• 1427049-21-5 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl-2,2,3,3,5,5,6,6-d8)butoxy]-1H-quinolin-2-one 
• 913614-15-0 4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butan-1-ol 

Relevant articles and documents

Synthesis method of 4-bromobenzo[b]thiophene

The invention discloses a novel synthesis method of 4-bromobenzo[b]thiophene. 2-bromo-6-fluorobenzaldehyde used as a raw material and chloro or bromo methyl-mercaptan undergo an etherification reaction to obtain 2-chloro(bromo) methylether-6-bromobenzaldehyde, then a Wittig reaction is carried out to obtain a target compound 4-bromobenzo[b]thiophene, and the crude product is refined and purified to obtain the high-purity product. The method has the advantages of mild reaction conditions, easiness in industrial production, good quality and high yield of the product, environmental friendliness and the like.

Base-catalyzed aryl halide isomerization enables the 4-selective substitution of 3-bromopyridines

The base-catalyzed isomerization of simple aryl halides is presented and utilized to achieve the 4-selective etherification, hydroxylation and amination of 3-bromopyridines. Mechanistic studies support isomerization of 3-bromopyridines to 4-bromopyridines proceedsviapyridyne intermediates and that 4-substitution selectivity is driven by a facile aromatic substitution reaction. Useful features of a tandem aryl halide isomerization/selective interception approach to aromatic functionalization are demonstrated. Example benefits include the use of readily available and stable 3-bromopyridines in place of less available and stable 4-halogenated congeners and the ability to converge mixtures of 3- and 5-bromopyridines to a single 4-substituted product.

HETEROCYCLIC COMPOUNDS, PROCESS FOR PREPARATION OF THE SAME AND USE THEREOF

The present invention provides a heterocyclic compound represented by the formula (I), its stereoisomers, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions thereof, and their use in preparing a medicament for the prevention and/or treatment of central nervous system disease.