110543-98-1

Basic information

• Product Name: ETHYL5-ACETOXY-6-BROMO-2-(BROMOMETHYL)-1-METHYLINDOLE-3-.
• Synonyms: ETHYL5-ACETOXY-6-BROMO-2-(BROMOMETHYL)-1-METHYLINDOLE-3-.;Ethyl 5-acetoxy-6-bromo-2-(bromomethyl)-1-methyl-1H-indole-3-carboxylate;Ethyl5-acetyloxy-6-bromo-2-bromomethyl-1-methylindole-3- Carboxylate;Ethyl 5-Acetoxy-6-broMo-2-(broMoMethyl)-1-Methylindole-3-carboxylate;Ethyl 5-acetoxy-6-broMo-2-broMoMethyl-1-Methylindo;5-acetoxy-6-bromo-2-(bromomethyl)-1-methyl-1H-indole-3-carboxylate
• CAS NO: 110543-98-1
• Molecular Formula: C₁₅H₁₅Br₂NO₄
• Molecular Weight: 433.09
• Product Categories: arbidol
• Mol File: 110543-98-1.mol
• Article Data: 11

Chemical Properties

• Melting Point: 179---180℃
• Boiling Point: 529.8 °C at 760 mmHg
• Flash Point: 274.2 °C
• Appearance: white crystalline power
• Density: 1.67 g/cm³
• Vapor Pressure: 2.62E-11mmHg at 25°C
• Refractive Index: 1.611
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: ETHYL5-ACETOXY-6-BROMO-2-(BROMOMETHYL)-1-METHYLINDOLE-3-.(CAS DataBase Reference)
• NIST Chemistry Reference: ETHYL5-ACETOXY-6-BROMO-2-(BROMOMETHYL)-1-METHYLINDOLE-3-.(110543-98-1)
• EPA Substance Registry System: ETHYL5-ACETOXY-6-BROMO-2-(BROMOMETHYL)-1-METHYLINDOLE-3-.(110543-98-1)

Safety Data

• Hazardous Substances Data: 110543-98-1(Hazardous Substances Data)

Usage

General Description

ETHYL5-ACETOXY-6-BROMO-2-(BROMOMETHYL)-1-METHYLINDOLE-3- is a complex organic compound that consists of ethyl, acetoxy, bromo, and methyl groups attached to a 1-methylindole core structure. The compound also contains a bromomethyl group, which further adds to its complexity. These chemical groups confer different properties to the compound, making it potentially useful in various applications such as pharmaceuticals, agrochemicals, and materials science. Its precise chemical structure and properties would need to be further analyzed and studied in detail for a more specific understanding of its potential uses and effects.

InChI:InChI=1/C15H15Br2NO4/c1-4-21-15(20)14-9-5-13(22-8(2)19)10(17)6-11(9)18(3)12(14)7-16/h5-6H,4,7H2,1-3H3

Synthetic route

1,2-dimethyl-5-acetoxy-1H-indole-3-carboxylic acid ethyl ester (40945-79-7) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
With bromine In tetrachloromethane for 16h; Inert atmosphere; Reflux;	99%
With bromine In tetrachloromethane for 2h; Heating;	87%
With bromine; dibenzoyl peroxide In chloroform for 3h; Reagent/catalyst; Reflux;	85%

1,2-dimethyl-5-acetoxy-1H-indole-3-carboxylic acid ethyl ester (40945-79-7) → 5-acetoxy-6,7-dibromo-2-bromomethyl-1-methyl-1H-indole-3-carboxylic acid ethyl ester (1312943-26-2) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
With bromine In 1,2-dichloro-ethane at 85℃; for 4h;	A 28% B 20 %Chromat.
With bromine In 1,2-dichloro-ethane at 85℃; for 3h;	A 23 %Chromat. B 53 %Chromat.

mecarbinate (15574-49-9) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine 2: bromine / tetrachloromethane / Heating View Scheme
Multi-step reaction with 2 steps 1: sodium acetate / dichloromethane / 3 h / Reflux 2: hydrogen bromide; dihydrogen peroxide / 1,2-dichloro-ethane / 4.5 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: 4 h / Reflux 2: [RhCl2(p-cymene)]2; N-Bromosuccinimide / water; N,N-dimethyl acetamide / 24 h / 90 °C / Inert atmosphere View Scheme

C14H17NO4 → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate; palladium diacetate; copper diacetate / N,N-dimethyl-formamide / 3 h / 80 °C 2: potassium carbonate / N,N-dimethyl-formamide / 6 h / 100 °C 3: dibenzoyl peroxide; bromine / chloroform / 3 h / Reflux View Scheme

ethyl 5-acetyloxy-2-methyl-1H-indole-3-carboxylate (20862-91-3) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 6 h / 100 °C 2: dibenzoyl peroxide; bromine / chloroform / 3 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: sodium hydride / N,N-dimethyl-formamide / 1.5 h / Inert atmosphere; Cooling with ice 2: bromine / tetrachloromethane / 16 h / Inert atmosphere; Reflux View Scheme

4-nitro-phenol (100-02-7) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions

Yield

Multi-step reaction with 6 steps 1: pyridine / acetone / 4 h / 20 °C / Reflux 2: iron; ammonium chloride / ethanol; water / 2 h / Reflux 3: indium(III) bromide / dichloromethane / 3 h / Reflux 4: potassium carbonate; palladium diacetate; copper diacetate / N,N-dimethyl-formamide / 3 h / 80 °C 5: potassium carbonate / N,N-dimethyl-formamide / 6 h / 100 °C 6: dibenzoyl peroxide; bromine / chloroform / 3 h / Reflux View Scheme

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + thiophenol (108-98-5) → 6-bromo-5-hydroxy-1-methyl-2-phenylthiomethylindole-3-carboxylic acid ethyl ester (131707-24-9)

Conditions	Yield
With potassium hydroxide In methanol for 3h; Ambient temperature;	96.4%
Stage #1: thiophenol With sodium hydroxide In methanol for 2h; Stage #2: 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester In methanol for 3h;	90.8%
Stage #1: 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester; thiophenol With sodium hydroxide In methanol at 15 - 20℃; for 1h; Stage #2: With acetic acid In methanol; acetone for 1h; Reflux;	88.6%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
In benzene for 22h; Ambient temperature;	91.9%

4-nitro-phenol (100-02-7) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 5-Acetoxy-6-bromo-1-methyl-2-(4-nitro-phenoxymethyl)-1H-indole-3-carboxylic acid ethyl ester (135980-83-5)

Conditions	Yield
With potassium hydroxide In acetone for 5h; Heating;	79.2%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + 2-mercapto-4-hydroxy-5-ethoxycarbonylpyrimidine sodium salt → 1-methyl-2-(4-hydroxy-5-ethoxycarbonylpyrimidyl-2)thiomethyl-3-ethoxycarbonyl-5-hydroxy-6-bromoindole

Conditions	Yield
In N,N-dimethyl-formamide for 0.5h; Ambient temperature;	77.1%

4-chloro-aniline (106-47-8) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 5-Acetoxy-6-bromo-2-[(4-chloro-phenylamino)-methyl]-1-methyl-1H-indole-3-carboxylic acid ethyl ester (132629-02-8)

Conditions	Yield
With triethylamine In benzene at 20℃;	76.8%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + phenol (108-95-2) → 5-Acetoxy-6-bromo-1-methyl-2-phenoxymethyl-1H-indole-3-carboxylic acid ethyl ester (135980-84-6) + 1-methyl-2-phenoxy-3-ethoxycarbonyl-5-(1-methyl-3-ethoxycarbonyl-5-acetoxy-6-bromoindolyl-2-methoxy)-6-bromoindole (135980-77-7)

Conditions	Yield
With potassium hydroxide In acetone for 5h; Heating;	A 72.5% B 4.1%

4-methoxy-aniline (104-94-9) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 5-Acetoxy-6-bromo-2-[(4-methoxy-phenylamino)-methyl]-1-methyl-1H-indole-3-carboxylic acid ethyl ester (132629-01-7)

Conditions	Yield
With triethylamine In benzene at 20℃;	71.1%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + aniline (62-53-3) → 5-Acetoxy-6-bromo-1-methyl-2-phenylaminomethyl-1H-indole-3-carboxylic acid ethyl ester (132629-00-6) + C30H31Br2N3O8

Conditions	Yield
With triethylamine In benzene at 20℃;	A 69.1% B 3.2%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + 4-methoxy-phenol (150-76-5) → 5-Acetoxy-6-bromo-2-(4-methoxy-phenoxymethyl)-1-methyl-1H-indole-3-carboxylic acid ethyl ester (135980-85-7)

Conditions	Yield
With potassium hydroxide In acetone for 5h; Heating;	68.3%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + N-methylaniline (100-61-8) → 5-Acetoxy-6-bromo-1-methyl-2-[(methyl-phenyl-amino)-methyl]-1H-indole-3-carboxylic acid ethyl ester (132628-99-0)

Conditions	Yield
With triethylamine In benzene at 20℃;	65%

4-bromo-phenol (106-41-2) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 5-Acetoxy-6-bromo-2-(4-bromo-phenoxymethyl)-1-methyl-1H-indole-3-carboxylic acid ethyl ester (135980-82-4)

Conditions	Yield
With potassium hydroxide In acetone for 5h; Heating;	64.5%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + thiourea (17356-08-0) → 1-methyl-2-thioureidomethyl-3-ethoxycarbonyl-5-acetoxy-6-bromoindole hydrobromide

Conditions	Yield
In ethanol for 24h; Heating;	64.2%

3-aminothiophenol (22948-02-3) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → ethyl 2-(((3-aminophenyl)thio)methyl)-6-bromo-5-hydroxy-1-methyl-1H-indole-3-carboxylate

Conditions	Yield
Stage #1: 3-aminothiophenol With potassium hydroxide In methanol at 20℃; for 0.25h; Inert atmosphere; Stage #2: 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester In methanol; dichloromethane for 3h; Inert atmosphere; Cooling with ice;	62%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + 4-nitro-aniline (100-01-6) → 5-Acetoxy-6-bromo-1-methyl-2-[(4-nitro-phenylamino)-methyl]-1H-indole-3-carboxylic acid ethyl ester (132629-03-9)

Conditions	Yield
With triethylamine In benzene at 20℃;	60.1%

1,2-dimethyl-5-acetoxy-1H-indole-3-carboxylic acid ethyl ester (40945-79-7) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
With bromine In tetrachloromethane for 16h; Inert atmosphere; Reflux;	99%
With bromine In tetrachloromethane for 2h; Heating;	87%
With bromine; dibenzoyl peroxide In chloroform for 3h; Reagent/catalyst; Reflux;	85%

1,2-dimethyl-5-acetoxy-1H-indole-3-carboxylic acid ethyl ester (40945-79-7) → 5-acetoxy-6,7-dibromo-2-bromomethyl-1-methyl-1H-indole-3-carboxylic acid ethyl ester (1312943-26-2) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
With bromine In 1,2-dichloro-ethane at 85℃; for 4h;	A 28% B 20 %Chromat.
With bromine In 1,2-dichloro-ethane at 85℃; for 3h;	A 23 %Chromat. B 53 %Chromat.

mecarbinate (15574-49-9) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine 2: bromine / tetrachloromethane / Heating View Scheme
Multi-step reaction with 2 steps 1: sodium acetate / dichloromethane / 3 h / Reflux 2: hydrogen bromide; dihydrogen peroxide / 1,2-dichloro-ethane / 4.5 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: 4 h / Reflux 2: [RhCl2(p-cymene)]2; N-Bromosuccinimide / water; N,N-dimethyl acetamide / 24 h / 90 °C / Inert atmosphere View Scheme

C14H17NO4 → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate; palladium diacetate; copper diacetate / N,N-dimethyl-formamide / 3 h / 80 °C 2: potassium carbonate / N,N-dimethyl-formamide / 6 h / 100 °C 3: dibenzoyl peroxide; bromine / chloroform / 3 h / Reflux View Scheme

ethyl 5-acetyloxy-2-methyl-1H-indole-3-carboxylate (20862-91-3) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 6 h / 100 °C 2: dibenzoyl peroxide; bromine / chloroform / 3 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: sodium hydride / N,N-dimethyl-formamide / 1.5 h / Inert atmosphere; Cooling with ice 2: bromine / tetrachloromethane / 16 h / Inert atmosphere; Reflux View Scheme

4-nitro-phenol (100-02-7) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions

Yield

Multi-step reaction with 6 steps 1: pyridine / acetone / 4 h / 20 °C / Reflux 2: iron; ammonium chloride / ethanol; water / 2 h / Reflux 3: indium(III) bromide / dichloromethane / 3 h / Reflux 4: potassium carbonate; palladium diacetate; copper diacetate / N,N-dimethyl-formamide / 3 h / 80 °C 5: potassium carbonate / N,N-dimethyl-formamide / 6 h / 100 °C 6: dibenzoyl peroxide; bromine / chloroform / 3 h / Reflux View Scheme

4-nitrophenol acetate (830-03-5) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: iron; ammonium chloride / ethanol; water / 2 h / Reflux 2: indium(III) bromide / dichloromethane / 3 h / Reflux 3: potassium carbonate; palladium diacetate; copper diacetate / N,N-dimethyl-formamide / 3 h / 80 °C 4: potassium carbonate / N,N-dimethyl-formamide / 6 h / 100 °C 5: dibenzoyl peroxide; bromine / chloroform / 3 h / Reflux View Scheme

p-aminophenyl acetate (13871-68-6) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: indium(III) bromide / dichloromethane / 3 h / Reflux 2: potassium carbonate; palladium diacetate; copper diacetate / N,N-dimethyl-formamide / 3 h / 80 °C 3: potassium carbonate / N,N-dimethyl-formamide / 6 h / 100 °C 4: dibenzoyl peroxide; bromine / chloroform / 3 h / Reflux View Scheme

ethyl 3-methylaminocrotonate (870-85-9) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1,2-dichloro-ethane / 8 h / Reflux 2: pyridine / acetone / 4 h / 30 °C 3: dibenzoyl peroxide; bromine / tetrachloromethane / 5 h / Reflux View Scheme
Multi-step reaction with 2 steps 2: bromine View Scheme

ethyl 5-hydroxy-2-methylindole-3-carboxylate (7598-91-6) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / 1 h / Inert atmosphere; Reflux 2: sodium hydride / N,N-dimethyl-formamide / 1.5 h / Inert atmosphere; Cooling with ice 3: bromine / tetrachloromethane / 16 h / Inert atmosphere; Reflux View Scheme

ethyl acetoacetate (141-97-9) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide 3: bromine View Scheme
Multi-step reaction with 4 steps 1: 3 h / 20 - 30 °C / Cooling with ice 2: zinc(II) chloride / dichloromethane / 4 h / 10 - 20 °C 3: sodium acetate / dichloromethane / 3 h / Reflux 4: hydrogen bromide; dihydrogen peroxide / 1,2-dichloro-ethane / 4.5 h / Reflux View Scheme

ethyl N-methyl β-aminocrotonate (65578-36-1) → 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: zinc(II) chloride / dichloromethane / 4 h / 10 - 20 °C 2: sodium acetate / dichloromethane / 3 h / Reflux 3: hydrogen bromide; dihydrogen peroxide / 1,2-dichloro-ethane / 4.5 h / Reflux View Scheme

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + thiophenol (108-98-5) → 6-bromo-5-hydroxy-1-methyl-2-phenylthiomethylindole-3-carboxylic acid ethyl ester (131707-24-9)

Conditions	Yield
With potassium hydroxide In methanol for 3h; Ambient temperature;	96.4%
Stage #1: thiophenol With sodium hydroxide In methanol for 2h; Stage #2: 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester In methanol for 3h;	90.8%
Stage #1: 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester; thiophenol With sodium hydroxide In methanol at 15 - 20℃; for 1h; Stage #2: With acetic acid In methanol; acetone for 1h; Reflux;	88.6%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + dibutylamine (111-92-2) → 1-Methyl-2-dibutylaminomethyl-3-ethoxycarbonyl-5-acetoxy-6-bromoindole (110566-59-1)

Conditions	Yield
In benzene for 22h; Ambient temperature;	91.9%

4-nitro-phenol (100-02-7) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 5-Acetoxy-6-bromo-1-methyl-2-(4-nitro-phenoxymethyl)-1H-indole-3-carboxylic acid ethyl ester (135980-83-5)

Conditions	Yield
With potassium hydroxide In acetone for 5h; Heating;	79.2%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + 2-mercapto-4-hydroxy-5-ethoxycarbonylpyrimidine sodium salt → 1-methyl-2-(4-hydroxy-5-ethoxycarbonylpyrimidyl-2)thiomethyl-3-ethoxycarbonyl-5-hydroxy-6-bromoindole

Conditions	Yield
In N,N-dimethyl-formamide for 0.5h; Ambient temperature;	77.1%

4-chloro-aniline (106-47-8) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 5-Acetoxy-6-bromo-2-[(4-chloro-phenylamino)-methyl]-1-methyl-1H-indole-3-carboxylic acid ethyl ester (132629-02-8)

Conditions	Yield
With triethylamine In benzene at 20℃;	76.8%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + phenol (108-95-2) → 5-Acetoxy-6-bromo-1-methyl-2-phenoxymethyl-1H-indole-3-carboxylic acid ethyl ester (135980-84-6) + 1-methyl-2-phenoxy-3-ethoxycarbonyl-5-(1-methyl-3-ethoxycarbonyl-5-acetoxy-6-bromoindolyl-2-methoxy)-6-bromoindole (135980-77-7)

Conditions	Yield
With potassium hydroxide In acetone for 5h; Heating;	A 72.5% B 4.1%

4-methoxy-aniline (104-94-9) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 5-Acetoxy-6-bromo-2-[(4-methoxy-phenylamino)-methyl]-1-methyl-1H-indole-3-carboxylic acid ethyl ester (132629-01-7)

Conditions	Yield
With triethylamine In benzene at 20℃;	71.1%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + aniline (62-53-3) → 5-Acetoxy-6-bromo-1-methyl-2-phenylaminomethyl-1H-indole-3-carboxylic acid ethyl ester (132629-00-6) + C30H31Br2N3O8

Conditions	Yield
With triethylamine In benzene at 20℃;	A 69.1% B 3.2%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + 4-methoxy-phenol (150-76-5) → 5-Acetoxy-6-bromo-2-(4-methoxy-phenoxymethyl)-1-methyl-1H-indole-3-carboxylic acid ethyl ester (135980-85-7)

Conditions	Yield
With potassium hydroxide In acetone for 5h; Heating;	68.3%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + N-methylaniline (100-61-8) → 5-Acetoxy-6-bromo-1-methyl-2-[(methyl-phenyl-amino)-methyl]-1H-indole-3-carboxylic acid ethyl ester (132628-99-0)

Conditions	Yield
With triethylamine In benzene at 20℃;	65%

4-bromo-phenol (106-41-2) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 5-Acetoxy-6-bromo-2-(4-bromo-phenoxymethyl)-1-methyl-1H-indole-3-carboxylic acid ethyl ester (135980-82-4)

Conditions	Yield
With potassium hydroxide In acetone for 5h; Heating;	64.5%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + thiourea (17356-08-0) → 1-methyl-2-thioureidomethyl-3-ethoxycarbonyl-5-acetoxy-6-bromoindole hydrobromide

Conditions	Yield
In ethanol for 24h; Heating;	64.2%

3-aminothiophenol (22948-02-3) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → ethyl 2-(((3-aminophenyl)thio)methyl)-6-bromo-5-hydroxy-1-methyl-1H-indole-3-carboxylate

Conditions	Yield
Stage #1: 3-aminothiophenol With potassium hydroxide In methanol at 20℃; for 0.25h; Inert atmosphere; Stage #2: 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester In methanol; dichloromethane for 3h; Inert atmosphere; Cooling with ice;	62%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + 4-nitro-aniline (100-01-6) → 5-Acetoxy-6-bromo-1-methyl-2-[(4-nitro-phenylamino)-methyl]-1H-indole-3-carboxylic acid ethyl ester (132629-03-9)

Conditions	Yield
With triethylamine In benzene at 20℃;	60.1%

3-methoxybenzenethiol (15570-12-4) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → ethyl 5-acetyloxy-6-bromo-2-(((3-methoxyphenyl)thio)methyl)-1-methyl-1H-indole-3-carboxylate

Conditions	Yield
With sodium carbonate In ethyl acetate at 50℃; for 2h; Inert atmosphere;	59%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) + 2-Naphthalenethiol (91-60-1) → C23H20BrNO3S

Conditions	Yield
Stage #1: 2-Naphthalenethiol With potassium hydroxide In methanol at 20℃; for 0.25h; Inert atmosphere; Stage #2: 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester In methanol; dichloromethane for 3h; Inert atmosphere; Cooling with ice;	50%

3-mercaptophenol (40248-84-8) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → ethyl 5-acetyloxy-6-bromo-2-(((3-hydroxyphenyl)thio)methyl)-1-methyl-1H-indole-3-carboxylate

Conditions	Yield
With sodium carbonate In ethyl acetate at 100℃; for 5h; Inert atmosphere;	44%

5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 5-acetoxy-6,7-dibromo-2-bromomethyl-1-methyl-1H-indole-3-carboxylic acid ethyl ester (1312943-26-2)

Conditions	Yield
With bromine In 1,2-dichloro-ethane at 85℃; for 4.5h;	28%

ortho-mercaptophenol (1121-24-0) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → ethyl 6-bromo-5-hydroxy-2-(((2-hydroxyphenyl)thio)methyl)-1-methyl-1H-indole-3-carboxylate

Conditions	Yield
Stage #1: ortho-mercaptophenol; 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester With sodium carbonate In ethyl acetate at 50℃; for 2h; Inert atmosphere; Stage #2: With methanol; potassium hydroxide at 20℃; for 3h; Inert atmosphere;	18%

aniline hydrochloride (142-04-1) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → C30H31Br2N3O8

Conditions	Yield
In water for 3h; Heating;	10.6%

4-sulfanylphenol (637-89-8) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → ethyl 6-bromo-5-hydroxy-2-(((4-hydroxyphenyl)thio)methyl)-1-methyl-1H-indole-3-carboxylate

Conditions	Yield
Stage #1: 4-sulfanylphenol; 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester With sodium carbonate In ethyl acetate at 50℃; for 2h; Inert atmosphere; Stage #2: With methanol; potassium hydroxide at 20℃; for 3h; Inert atmosphere;	2%

morpholine (110-91-8) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 5-Acetoxy-6-bromo-1-methyl-2-morpholin-4-ylmethyl-1H-indole-3-carboxylic acid ethyl ester (110543-92-5)

Conditions	Yield
In benzene for 22h; Ambient temperature;
In benzene for 1h;

Thiophene-2-thiol (7774-74-5) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 1-methyl-2-(thienyl-2')-thiomethyl-3-ethoxycarbonyl-5-hydroxy-6-bromoindole

Conditions	Yield
With potassium hydroxide 1.) MeOH, RT, 10 min, 2.) MeOH, RT, 3 h; Yield given. Multistep reaction;

thiophene-3-thiol (7774-73-4) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 1-methyl-2-(thienyl-3')-thiomethyl-3-ethoxycarbonyl-5-hydroxy-6-bromoindole

Conditions	Yield
With potassium hydroxide 1.) MeOH, RT, 10 min, 2.) MeOH, RT, 3 h; Yield given. Multistep reaction;

2-Mercaptopyridine (2637-34-5) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 1-methyl-2-(pyridyl-2')-thiomethyl-3-ethoxycarbonyl-5-hydroxy-6-bromoindole

Conditions	Yield
With potassium hydroxide 1.) MeOH, RT, 10 min, 2.) MeOH, RT, 3 h; Yield given. Multistep reaction;

Cyclohexanethiol (1569-69-3) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 1-methyl-2-cyclohexylthiomethyl-3-ethoxycarbonyl-5-hydroxy-6-bromoindole

Conditions	Yield
With potassium hydroxide 1.) MeOH, RT, 10 min, 2.) MeOH, RT, 3 h; Yield given. Multistep reaction;

4-hydroxy-3,5-di-tert-butylthiophenol (950-59-4) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 1-methyl-2-(3',5'-di-tert-butyl-4'-hydroxyphenyl)-thiomethyl-3-ethoxycarbonyl-5-hydroxy-6-bromoindole

Conditions	Yield
With potassium hydroxide 1.) MeOH, RT, 10 min, 2.) MeOH, RT, 3 h; Yield given. Multistep reaction;

3-cyano-4,6-dimethyl-2-mercaptopyridine (54585-47-6) + 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid ethyl ester (110543-98-1) → 1-methyl-2-(3'-cyano-4',6'-dimethylpyridyl-2')-thiomethyl-3-ethoxycarbonyl-5-hydroxy-6-bromoindole

Conditions	Yield
With potassium hydroxide 1.) MeOH, RT, 10 min, 2.) MeOH, RT, 3 h; Yield given. Multistep reaction;

Upstream product

• 40945-79-7 1,2-dimethyl-5-acetoxy-1H-indole-3-carboxylic acid ethyl ester 
• 65578-36-1 ethyl N-methyl β-aminocrotonate 
• 7598-91-6 ethyl 5-hydroxy-2-methylindole-3-carboxylate 
• 870-85-9 ethyl 3-methylaminocrotonate 
• 13871-68-6 p-aminophenyl acetate 
• 830-03-5 4-nitrophenol acetate 
• 100-02-7 4-nitro-phenol 
• 20862-91-3 ethyl 5-acetyloxy-2-methyl-1H-indole-3-carboxylate 
• 15574-49-9 mecarbinate 
• 141-97-9 ethyl acetoacetate 

Downstream Products

• 153633-10-4 6,7-dibromo-4-dimethylaminomethyl-5-hydroxy-1-methyl-2-phenylsulfanyl-methyl-1H-indole-3-carboxylic acid ethyl ester 
• 1312943-24-0 (6,7-dibromo-3-ethoxycarbonyl-5-hydroxy-1-methyl-2-phenylsulfanylmethyl-1H-indol-4-ylmethyl)-dimethyl-ammonium chloride 
• 2126032-35-5 ethyl 6-bromo-4-((dimethylamino)methyl)-5-hydroxy-2-(((3-hydroxyphenyl)thio)methyl)-1-methyl-1H-indole-3-carboxylate 
• 842162-68-9 ethyl 6-bromo-5-hydroxy-2-(((3-methoxyphenyl)thio)methyl)-1-methyl-1H-indole-3-carboxylate 
• 131707-23-8 Arbidol hydrochloride 
• 135980-97-1 6-Bromo-4-dimethylaminomethyl-5-hydroxy-1-methyl-2-(4-nitro-phenoxymethyl)-1H-indole-3-carboxylic acid ethyl ester 
• 135980-94-8 6-Bromo-4-dimethylaminomethyl-5-hydroxy-2-(4-methoxy-phenoxymethyl)-1-methyl-1H-indole-3-carboxylic acid ethyl ester 
• 135980-95-9 6-Bromo-2-(4-bromo-phenoxymethyl)-4-dimethylaminomethyl-5-hydroxy-1-methyl-1H-indole-3-carboxylic acid ethyl ester 
• 135980-96-0 6-Bromo-2-(4-bromo-phenoxymethyl)-5-hydroxy-1-methyl-4-morpholin-4-ylmethyl-1H-indole-3-carboxylic acid ethyl ester 
• 135980-87-9 6-Bromo-5-hydroxy-1-methyl-2-(4-nitro-phenoxymethyl)-1H-indole-3-carboxylic acid ethyl ester 

Relevant articles and documents

SYNTHESIS OF A NEW ANTIVIRAL AGENT, ARBIDOLE

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Preparation method of arbidol intermediate

The invention discloses a preparation method of an arbidol intermediate. Ethyl acetoacetate, monomethylamine and p-benzoquinone used as initial raw materials undergo methylation, cyclization, acetylation, bromination and benzene vulcanization to prepare the target compound ethyl 5-hydroxy-6-bromo-2-phenylthiomethyl-1-methylindole-3-carboxylate. The preparation method of the arbidol intermediate issimple and convenient to operate, cheap and easily available in raw materials, high in yield, low in cost, good in quality, environment-friendly, mild in reaction condition, high in safety productioncoefficient and suitable for large-scale industrial production.

ARBIDOL ANALOGS WITH IMPROVED INFLUENZA HEMAGGLUTININ POTENCY

The invention provides a series of analogs of arbidol having enhanced binding activity with respect to influenza hemagglutinin. Accordingly, the invention can provide a method of inhibiting the bioactivity of viral hemagglutinin activity, which is an essential step in the entry of infectious viral particles into host cells. The invention also can provide a method of treatment of influence, comprising administering an effective amount of a compound of formula (A), wherein X is S or O, to a patient afflicted therewith.