5118-13-8

Usage

Uses

Used in Pharmaceutical Industry:
4-BROMO-BENZO[B]THIOPHENE is used as an important intermediate in the synthesis of the drug ipiprazole, which is a medication used for the treatment of schizophrenia. Its unique structure allows it to play a crucial role in the development of this antipsychotic drug, helping to manage the symptoms and improve the quality of life for individuals suffering from this mental disorder.

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.

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

• 17402-83-4 benzo[B]thiophen-4-ylamine 
• 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 
• 10133-34-3 4-nitrobenzene[b]thiophene 
• 18044-91-2 benzo[b]thiophen-5-yl-acetamide 
• 127491-04-7 4-nitro-benzo[b]thiophen-5-ylamine 
• 6320-01-0 3-Bromothiophenol 
• 2032-35-1 Bromoacetaldehyde diethyl acetal 
• 67713-23-9 2,6-dibromobenzaldehyde 
• 4923-87-9 5-bromobenzo[b]thiophene 
• 95-15-8 Benzo[b]thiophene 
• 93103-82-3 4-bromobenzo[b]thiophene-2-carboxylic acid ethyl ester 
• 360575-28-6 2-bromo-6-fluorobenzaldehyde 

Downstream Products

• 154650-81-4 benzo[b]thiophene-6-carbonitrile 
• 17347-34-1 benzo[b]thiophene-4-carbonitrile 
• 88341-06-4 4-acetylbenzothiophen 
• 864684-52-6 4-[(E)-2-phenylvinyl]benzo[b]thiophene 
• 10133-25-2 benzo[b]thiophene-4-carboxaldehyde 
• 913611-97-9 Brexpiprazole 
• 1191901-07-1 tert-butyl 4-(benzo[b]thiophen-4-yl)piperazine-1-carboxylate 
• 2635-75-8 benzothiophene-4-acetic acid 
• 10134-95-9 benzothiophen-4-carboxic acid 

Relevant academic research and scientific papers

Synthesis method of brexpiprazole intermediate 4-bromobenzo[b]thiophene

The invention belongs to the field of chemical pharmacy, and particularly discloses a synthesis method of a brexpiprazole intermediate 4-bromobenzo[b]thiophene. The synthesis method comprises: carrying out a cyclization reaction with mercaptoacetic acid by using 2-bromo-6-fluorobenzaldehyde as a raw material, and carrying out a deacidification reaction to obtain the 4-bromobenzo[b]thiophene. According to the invention, triethylene diamine is used as a decarboxylation catalyst, and replaces an oxine-copper system, so that the reaction temperature is low, impurities are few, and the product yield is high; and the triethylene diamine can be recycled, so that the production cost is reduced, the generation of three wastes is reduced, and the method is environment-friendly.

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.

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.

Synthesis method of brexpiprazole intermediate 4-bromo-benzo[B]thiophene

The invention discloses a synthesis method of a brexpiprazole intermediate 4-bromo-benzo [B] thiophene. According to the synthesis method, benzothiophene, metal bromide, organic acid and hydrogen peroxide are enabled to react to obtain the 4-bromo-benzo[B]thiophene under the action of a catalyst. A reaction process includes: 1) mixing the benzothiophene, the organic acid and the catalyst, introducing protection gas, controlling pressure within a range from 2 to 4 barometric pressure and temperature within a range from 60 to 85 DEG C, dripping the hydrogen peroxide at a constant speed for 25-35minutes, starting to drip a mixture A composed of the metal bromide, water and an active agent at a constant speed when the hydrogen peroxide accounts for 10-18% of the total volume, controlling dripping time of the mixture A within 35-45 minutes, after operation is over, heating the temperature to 110-125 DEG C, enlarging the pressure to 8-10 barometric pressure, and continuing the reaction for15-22 hours before reaction is over; 2) cooling a system, adding the system into water which is as 2-4 times as the system in volume, extracting with a solvent B, drying an extracting solution with adrying agent, and concentrating by evaporating the solvent to obtain the product. The synthesis method is short in process, low in cost and barely free from production of three wastes.

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.

BIARYL DERIVATIVE AS GPR120 AGONIST

The present invention relates to a biaryl derivative expressed by the chemical formula 1, a method for producing the biaryl derivative, a pharmaceutical composition comprising same, and use of same, the biaryl derivative expressed by the chemical formula 1, as a GPR120 agonist, promoting GLP-1 generation in the gastro-intestinal tract, reducing insulin resistance in the liver, muscles and the like from anti-inflammatory activity in the macrophage, pancreatic cells and the like, and allowing effective use in prevention or treatment of inflammation or metabolic diseases such as diabetes, complications from diabetes, obesity, non-alcoholic fatty liver disease, fatty liver disease, and osteoporosis.

An improved synthesis of 4-(1-Piperazinyl)benzo[ b ]thiophene Dihydrochloride

2-Chloro-6-fluorobenzaldehyde was converted to 4-(1-piperazinyl)benzo[b]thiophene dihydrochloride (18), an intermediate in the synthesis of brexpiprazole, via a five-step sequence in 54% overall yield. This procedure requires no expensive catalyst and avoids the side products produced in the coupling step in the reported process. Several kilograms of compound 18 were prepared using this economical and scalable process.

CONJUGATED POLYMERS

The invention relates to novel conjugated polymers containing one or more repeating units derived from indacenodibenzothiophene or dithia-dicyclopenta-dibenzothiophene, to methods for their preparation and educts or intermediates used therein, to polymer blends, mixtures and formulations containing them, to the use of the polymers, polymer blends, mixtures and formulations as organic semiconductors in organic electronic (OE) devices, especially in organic photovoltaic (OPV) devices and organic photodetectors (OPD), and to OE, OPV and OPD devices comprising these polymers, polymer blends, mixtures or formulations.

INHIBITORS OF THE KYNURENINE PATHWAY

The present application provides novel inhibitors of indoleamine 2,3-dioxygenase-1 and/or indoleamine 2,3-dioxygenase-2 and/or tryptophan 2,3-dioxygenase, metabolites thereof, and phannaceutically acceptable salts or prodrugs thereof. Also provided are methods for preparing these compounds. A therapeutically effective amount of one or more of the compounds of formula (I) is useful in treating diseases resulting from dysregulation of the kynurenine pathway. Compounds of formula (I) act by inhibiting the enzymatic activity or expression of indoleamine 2,3-dioxygenase-1 and/or indoleamine 2,3-dioxygenase-2 and/or tryptophan 2,3-dioxygenase.

A continuous protodecarboxylation of heteroaromatic carboxylic acids in sulfolane

A versatile, scalable method for the decarboxylation of indole-2-carboxylic acids has been found. With one equivalent of DBU in sulfolane, indole-2-carboxylic acid derivatives were cleanly decarboxylated in a 316 stainless steel tube reactor at 300 °C within 20 min. The corresponding indole derivatives were obtained in good yields. It was also found that indole-2-carboxylic acid (1) can be decarboxylated in either pure sulfolane or sulfolane with 3% water at 300 °C within 20 min. (1) The decarboxylation with one equivalent of DBU could successfully be transferred to benzo[b]thiophene-2-carboxylic acid derivatives if a prolonged reaction time was used. (2) Picolinic acid could also be decarboxylated in sulfolane with 3% water, and thiophene-2-carboxylic acid was smoothly decarboxylated with DABCO instead of DBU. (3) Benzoic acid derivatives were either inert or decomposed under the reaction conditions.