115661-82-0

Usage

Uses

Used in Pharmaceutical Industry:
7-Indolinecarbonitrile is used as a reactant for the preparation of silodosin (S465000), an α1a-adrenoceptor antagonist. It plays a crucial role in the treatment of benign prostatic hyperplasia (BPH), a common condition in aging men that causes enlarged prostate and urinary problems. The compound's reactivity and structural features make it a valuable building block in the development of new drugs targeting this medical condition.

InChI:InChI=1/C9H8N2/c10-6-8-3-1-2-7-4-5-11-9(7)8/h1-3,11H,4-5H2

Synthetic route

1-indoline (496-15-1) + methanolic sodium methanolate + trichloroacetonitrile (545-06-2) → 7-cyanoindoline (115661-82-0)

Conditions	Yield
With BCl3 In methanol; hexane; pentan-1-ol; water; toluene	60.5%

1-indoline (496-15-1) + trichloroacetonitrile (545-06-2) → 7-cyanoindoline (115661-82-0)

Conditions	Yield
With boron trichloride; potassium carbonate In methanol; dichloromethane; toluene	58%

7-cyanoindoline (115661-82-0) + 3-chloropropyl benzoate (942-95-0) → 1-(benzoyloxypropyl)-7-cyanoindoline hydrochloride

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 100℃; for 10h;	91%

7-cyanoindoline (115661-82-0) + 3-chloropropyl benzoate (942-95-0) → 1-[3-(benzoyloxy)propyl]-7-cyanoindoline

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate; potassium iodide In N,N-dimethyl acetamide at 140℃; for 24h; Inert atmosphere;	84%

7-cyanoindoline (115661-82-0) → 1H-indole-7-carbonitrile (96631-87-7)

Conditions	Yield
With oxygen; sodium t-butanolate In dimethyl sulfoxide at 60℃; under 760.051 Torr; for 4h;	58%

7-cyanoindoline (115661-82-0) → 2,3-dihydro-1H-indole-7-carboxylic acid (15861-40-2)

Conditions	Yield
With sulfuric acid

7-cyanoindoline (115661-82-0) → (2-{1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-7-cyano-2,3-dihydro-1H-indol-5-yl}-1-methyl-2-oxo-ethyl)-carbamic acid ethyl ester (1269801-81-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 70 °C 2.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / -15 - 20 °C / Inert atmosphere 2.2: -15 °C View Scheme
Multi-step reaction with 2 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 70 °C 2.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 2.2: -15 °C View Scheme

7-cyanoindoline (115661-82-0) → (2-{1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-7-cyano-2,3-dihydro-1H-indol-5-yl}-1-methyl-ethyl)-carbamic acid ethyl ester (1269801-83-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 70 °C 2.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / -15 - 20 °C / Inert atmosphere 2.2: -15 °C 3.1: trifluoroacetic acid; triethylsilane / toluene / 6 h / 25 - 30 °C View Scheme
Multi-step reaction with 3 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 70 °C 2.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 2.2: -15 °C 3.1: trifluoroacetic acid; triethylsilane / toluene / 6 h / 25 - 30 °C View Scheme

7-cyanoindoline (115661-82-0) → (2-{1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-7-carbamoyl-2,3-dihydro-1H-indol-5-yl}-1-methyl-ethyl)-carbamic acid ethyl ester (1269801-84-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 70 °C 2.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / -15 - 20 °C / Inert atmosphere 2.2: -15 °C 3.1: trifluoroacetic acid; triethylsilane / toluene / 6 h / 25 - 30 °C 4.1: dihydrogen peroxide / dimethyl sulfoxide / 0.25 h / 25 - 30 °C View Scheme
Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 70 °C 2.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 2.2: -15 °C 3.1: trifluoroacetic acid; triethylsilane / toluene / 6 h / 25 - 30 °C 4.1: dihydrogen peroxide / dimethyl sulfoxide / 0.25 h / 25 - 30 °C 4.2: 3 h / 25 - 30 °C View Scheme

7-cyanoindoline (115661-82-0) → 5-(2-amino-propyl)-1-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2,3-dihydro-1H-indole-7-carboxylic acid amide (1269801-85-5)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 70 °C 2.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / -15 - 20 °C / Inert atmosphere 2.2: -15 °C 3.1: trifluoroacetic acid; triethylsilane / toluene / 6 h / 25 - 30 °C 4.1: dihydrogen peroxide / dimethyl sulfoxide / 0.25 h / 25 - 30 °C 5.1: potassium hydroxide / toluene / 3 h / Reflux View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 70 °C 2.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 2.2: -15 °C 3.1: trifluoroacetic acid; triethylsilane / toluene / 6 h / 25 - 30 °C 4.1: dihydrogen peroxide / dimethyl sulfoxide / 0.25 h / 25 - 30 °C 4.2: 3 h / 25 - 30 °C 5.1: potassium hydroxide; water / toluene / 3 h / Reflux View Scheme

7-cyanoindoline (115661-82-0) + N-<3-(tert-butyldimethylsiloxy)propyl>-p-toluenesulfonate (115306-83-7) → 1-[3-(t-butyl-dimethyl-silanyloxy)-propyl]-2,3-dihydro-1H-indole-7-carbonitrile (1269801-75-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 70℃;
With potassium carbonate In N,N-dimethyl-formamide at 70℃;

7-cyanoindoline (115661-82-0) → silodosin (160970-54-7)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: triethylamine / N,N-dimethyl-formamide / 10 h / 100 °C 2.1: aluminum (III) chloride / dichloromethane / 0.17 h / 0 °C 2.2: 5 h / 30 °C 3.1: triethylsilane; trifluoroacetic acid / toluene / 6 h / 30 °C 4.1: hydrogen; palladium 10% on activated carbon / methanol / 2 h / 40 °C / 750.08 Torr 5.1: potassium carbonate; tetrabutylammomium bromide; potassium iodide / water / 6 h / 80 °C 6.1: dihydrogen peroxide; sodium hydroxide / dimethyl sulfoxide / 4 h / 18 - 30 °C View Scheme

7-cyanoindoline (115661-82-0) → 5-[(2R)-2-(benzylamino)-1-propanoyl]-1-[3-(benzoyloxy)propyl]-7-cyanoindoline

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / N,N-dimethyl-formamide / 10 h / 100 °C 2.1: aluminum (III) chloride / dichloromethane / 0.17 h / 0 °C 2.2: 5 h / 30 °C View Scheme

7-cyanoindoline (115661-82-0) → 5-[(2R)-2-(benzylamino)propyl]-1-[3-(benzoyloxy)propyl]-7-cyanoindoline

Conditions	Yield
Multi-step reaction with 3 steps 1.1: triethylamine / N,N-dimethyl-formamide / 10 h / 100 °C 2.1: aluminum (III) chloride / dichloromethane / 0.17 h / 0 °C 2.2: 5 h / 30 °C 3.1: triethylsilane; trifluoroacetic acid / toluene / 6 h / 30 °C View Scheme

7-cyanoindoline (115661-82-0) → 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-carbonitrile (239463-72-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine / N,N-dimethyl-formamide / 10 h / 100 °C 2.1: aluminum (III) chloride / dichloromethane / 0.17 h / 0 °C 2.2: 5 h / 30 °C 3.1: triethylsilane; trifluoroacetic acid / toluene / 6 h / 30 °C 4.1: hydrogen; palladium 10% on activated carbon / methanol / 2 h / 40 °C / 750.08 Torr View Scheme
Multi-step reaction with 4 steps 1.1: potassium iodide; potassium carbonate; tetrabutylammomium bromide / N,N-dimethyl acetamide / 24 h / 140 °C / Inert atmosphere 2.1: trichlorophosphate / 0.5 h / 0 °C / Inert atmosphere; Cooling with ice 2.2: 3 h / 25 °C 3.1: C24H22F3NO2 / tetrahydrofuran / 0.25 h / -10 °C / Inert atmosphere 3.2: 12 h / 0 °C 4.1: palladium 10% on activated carbon / methanol / 6 h / 50 °C / 3750.38 Torr View Scheme

7-cyanoindoline (115661-82-0) → 2,3-dihydro-1-[3-(benzoyloxy)propyl]-5-[(2R)-2-[[2-[(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-1H-indole-7-carbonitrile (885340-11-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: triethylamine / N,N-dimethyl-formamide / 10 h / 100 °C 2.1: aluminum (III) chloride / dichloromethane / 0.17 h / 0 °C 2.2: 5 h / 30 °C 3.1: triethylsilane; trifluoroacetic acid / toluene / 6 h / 30 °C 4.1: hydrogen; palladium 10% on activated carbon / methanol / 2 h / 40 °C / 750.08 Torr 5.1: potassium carbonate; tetrabutylammomium bromide; potassium iodide / water / 6 h / 80 °C View Scheme
Multi-step reaction with 5 steps 1.1: potassium iodide; potassium carbonate; tetrabutylammomium bromide / N,N-dimethyl acetamide / 24 h / 140 °C / Inert atmosphere 2.1: trichlorophosphate / 0.5 h / 0 °C / Inert atmosphere; Cooling with ice 2.2: 3 h / 25 °C 3.1: C24H22F3NO2 / tetrahydrofuran / 0.25 h / -10 °C / Inert atmosphere 3.2: 12 h / 0 °C 4.1: palladium 10% on activated carbon / methanol / 6 h / 50 °C / 3750.38 Torr 5.1: sodium carbonate / tert-butyl alcohol; ethanol / 34 h / 50 - 90 °C / Inert atmosphere View Scheme

7-cyanoindoline (115661-82-0) → C20H18N2O3

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium iodide; potassium carbonate; tetrabutylammomium bromide / N,N-dimethyl acetamide / 24 h / 140 °C / Inert atmosphere 2.1: trichlorophosphate / 0.5 h / 0 °C / Inert atmosphere; Cooling with ice 2.2: 3 h / 25 °C View Scheme

7-cyanoindoline (115661-82-0) → C22H23N3O5

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium iodide; potassium carbonate; tetrabutylammomium bromide / N,N-dimethyl acetamide / 24 h / 140 °C / Inert atmosphere 2.1: trichlorophosphate / 0.5 h / 0 °C / Inert atmosphere; Cooling with ice 2.2: 3 h / 25 °C 3.1: C24H22F3NO2 / tetrahydrofuran / 0.25 h / -10 °C / Inert atmosphere 3.2: 12 h / 0 °C View Scheme

7-cyanoindoline (115661-82-0) → 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carbonitrile (885340-13-6)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: potassium iodide; potassium carbonate; tetrabutylammomium bromide / N,N-dimethyl acetamide / 24 h / 140 °C / Inert atmosphere 2.1: trichlorophosphate / 0.5 h / 0 °C / Inert atmosphere; Cooling with ice 2.2: 3 h / 25 °C 3.1: C24H22F3NO2 / tetrahydrofuran / 0.25 h / -10 °C / Inert atmosphere 3.2: 12 h / 0 °C 4.1: palladium 10% on activated carbon / methanol / 6 h / 50 °C / 3750.38 Torr 5.1: sodium carbonate / tert-butyl alcohol; ethanol / 34 h / 50 - 90 °C / Inert atmosphere 6.1: sodium hydroxide / methanol / 2.75 h / 0 - 25 °C / Inert atmosphere 6.2: 2.5 h / 25 °C / Cooling with ice View Scheme

Upstream product

• 496-15-1 1-indoline 
• 545-06-2 trichloroacetonitrile 

Downstream Products

• 1423218-40-9 tert-butyl (2R)-(1-(1-(3-benzyloxypropyl)-7-cyanoindolin-5-yl)propane-2-yl)-N-(2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)carbamate 
• 1096141-54-6 1-(3-(benzyloxy)propyl)-5-bromoindoline-7-carbonitrile 
• 885340-11-4 2,3-dihydro-1-[3-(benzoyloxy)propyl]-5-[(2R)-2-[[2-[(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-1H-indole-7-carbonitrile 
• 239463-72-0 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-carbonitrile 
• 160970-54-7 silodosin 
• 15861-40-2 2,3-dihydro-1H-indole-7-carboxylic acid 

Relevant academic research and scientific papers

PROCESS FOR THE PREPARATION OF SILODOSIN

The present invention relates to a new process of preparation of Silodosin, or a pharmaceutically acceptable salt thereof. Another aspect of the invention concerns compounds of formula II: or their pharmaceutically acceptable salts thereof, and their use for the preparation of Silodosin or a pharmaceutically acceptable salt thereof.

Process for the production of 7-acylindoles

A process for the production of 7-acylindoles of the general formula: STR1 starting from indoline of the formula: STR2 Indoline is cyanized in a first stage to 7-cyanoindoline of the formula: STR3 The latter is catalytically dehydrogenated in a second stage to 7-cyanindole of the formula: STR4 The latter is then acylated in a third stage with an organometallic compound of the formula: into the end product according to formula I.

Process for ortho-cyanation of phenols or phenylamines

A process for ortho-cyanation of phenols or phenylamines which comprises reacting a phenyl compound having hydroxy or optionally substituted amino or cyclic amino, of which ortho position is vacant, with trichloroacetonitrile, C1 -C5 alkyl thiocyanate or C6 -C12 aryl thiocyanate in the presence of a boron trihalide and treating the resultant product with an alkali is provided, and said process is useful in the synthesis of intermediates for medicinals or pesticides.