160970-64-9

Basic information

• Product Name: Silodosin
• Synonyms: 2,3-Dihydro-1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-1H-indole-7-carboxamide;rac-Silodosin
• CAS NO: 160970-64-9
• Molecular Formula: C₂₅H₃₂F₃N₃O₄
• Molecular Weight: 495.5344896
• Mol File: 160970-64-9.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 601.4 °C at 760 mmHg
• Flash Point: 317.5 °C
• Appearance: colorless to pink solid
• Density: 1.249
• Vapor Pressure: 2.58E-15mmHg at 25°C
• Refractive Index: 1.552
• PKA: 14.85±0.10(Predicted)
• CAS DataBase Reference: Silodosin(CAS DataBase Reference)
• NIST Chemistry Reference: Silodosin(160970-64-9)
• EPA Substance Registry System: Silodosin(160970-64-9)

Safety Data

• Hazardous Substances Data: 160970-64-9(Hazardous Substances Data)

Usage

General Description

Silodosin is a medication that belongs to a class of drugs known as alpha-1 adrenergic blockers. It is primarily used to treat the symptoms of benign prostatic hyperplasia (BPH) by relaxing the muscles in the prostate and bladder. Silodosin works by blocking the alpha-1 adrenergic receptors, which are found in the smooth muscles of the prostate and bladder neck, leading to improved urine flow and reduced symptoms such as difficulty urinating, frequent urination, and a weak stream. It is important to follow the dosage and usage instructions provided by a healthcare professional when taking Silodosin in order to avoid potential side effects and interactions with other medications.

InChI:InChI=1/C25H32F3N3O4/c1-17(30-8-12-34-21-5-2-3-6-22(21)35-16-25(26,27)28)13-18-14-19-7-10-31(9-4-11-32)23(19)20(15-18)24(29)33/h2-3,5-6,14-15,17,30,32H,4,7-13,16H2,1H3,(H2,29,33)/t17-/m1/s1

Synthetic route

1-(3-hydroxypropyl)-5(R)-[2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]-ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carbonitrile → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions	Yield
With water; dihydrogen peroxide; sodium hydroxide In dimethyl sulfoxide at 0 - 25℃;	87%

C22H25N3O5 → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: acetic anhydride / tetrahydrofuran / 24 h / 70 °C 2: hydrogen; palladium 10% on activated carbon / methanol; tetrahydrofuran / 48 h / 40 °C 3: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 12 h / 20 °C 4: sodium hydroxide; water / methanol / 2 h / 20 °C 5: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

3-(indolin-1-yl)propan-1-ol → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions

Yield

Multi-step reaction with 11 steps 1.1: triethylamine / dichloromethane / 8 h / 0 - 25 °C / Inert atmosphere 2.1: trichlorophosphate / 1,2-dichloro-ethane / 1 h / 0 °C / Inert atmosphere 2.2: 2 h / 0 - 80 °C / Inert atmosphere 3.1: ammonium acetate; acetic acid / 4 h / 80 °C 4.1: sodium tetrahydroborate / dichloromethane; methanol / 1 h / 0 - 25 °C 5.1: trichlorophosphate / 1 h / 0 °C / Inert atmosphere 5.2: 2 h / 0 - 80 °C / Inert atmosphere 6.1: hydroxylamine hydrochloride; pyridine / tetrahydrofuran / 12 h / 70 °C 7.1: acetic anhydride / tetrahydrofuran / 24 h / 70 °C 8.1: hydrogen; palladium 10% on activated carbon / methanol; tetrahydrofuran / 48 h / 40 °C 9.1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 12 h / 20 °C 10.1: sodium hydroxide; water / methanol / 2 h / 20 °C 11.1: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

3-(indolin-1-yl)propyl benzoate → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions

Yield

Multi-step reaction with 10 steps 1.1: trichlorophosphate / 1,2-dichloro-ethane / 1 h / 0 °C / Inert atmosphere 1.2: 2 h / 0 - 80 °C / Inert atmosphere 2.1: ammonium acetate; acetic acid / 4 h / 80 °C 3.1: sodium tetrahydroborate / dichloromethane; methanol / 1 h / 0 - 25 °C 4.1: trichlorophosphate / 1 h / 0 °C / Inert atmosphere 4.2: 2 h / 0 - 80 °C / Inert atmosphere 5.1: hydroxylamine hydrochloride; pyridine / tetrahydrofuran / 12 h / 70 °C 6.1: acetic anhydride / tetrahydrofuran / 24 h / 70 °C 7.1: hydrogen; palladium 10% on activated carbon / methanol; tetrahydrofuran / 48 h / 40 °C 8.1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 12 h / 20 °C 9.1: sodium hydroxide; water / methanol / 2 h / 20 °C 10.1: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

1-(3-benzoyloxypropyl)-5-formyl-2,3-dihydroindole (350797-52-3) → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: ammonium acetate; acetic acid / 4 h / 80 °C 2.1: sodium tetrahydroborate / dichloromethane; methanol / 1 h / 0 - 25 °C 3.1: trichlorophosphate / 1 h / 0 °C / Inert atmosphere 3.2: 2 h / 0 - 80 °C / Inert atmosphere 4.1: hydroxylamine hydrochloride; pyridine / tetrahydrofuran / 12 h / 70 °C 5.1: acetic anhydride / tetrahydrofuran / 24 h / 70 °C 6.1: hydrogen; palladium 10% on activated carbon / methanol; tetrahydrofuran / 48 h / 40 °C 7.1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 12 h / 20 °C 8.1: sodium hydroxide; water / methanol / 2 h / 20 °C 9.1: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

1-(3-benzoyloxypropyl)-5-(2-nitro-1-propenyl)-2,3-dihydroindole (350797-53-4) → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sodium tetrahydroborate / dichloromethane; methanol / 1 h / 0 - 25 °C 2.1: trichlorophosphate / 1 h / 0 °C / Inert atmosphere 2.2: 2 h / 0 - 80 °C / Inert atmosphere 3.1: hydroxylamine hydrochloride; pyridine / tetrahydrofuran / 12 h / 70 °C 4.1: acetic anhydride / tetrahydrofuran / 24 h / 70 °C 5.1: hydrogen; palladium 10% on activated carbon / methanol; tetrahydrofuran / 48 h / 40 °C 6.1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 12 h / 20 °C 7.1: sodium hydroxide; water / methanol / 2 h / 20 °C 8.1: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

1-indoline (496-15-1) → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions

Yield

Multi-step reaction with 12 steps 1.1: potassium carbonate / acetonitrile / 12 h / 90 °C 2.1: triethylamine / dichloromethane / 8 h / 0 - 25 °C / Inert atmosphere 3.1: trichlorophosphate / 1,2-dichloro-ethane / 1 h / 0 °C / Inert atmosphere 3.2: 2 h / 0 - 80 °C / Inert atmosphere 4.1: ammonium acetate; acetic acid / 4 h / 80 °C 5.1: sodium tetrahydroborate / dichloromethane; methanol / 1 h / 0 - 25 °C 6.1: trichlorophosphate / 1 h / 0 °C / Inert atmosphere 6.2: 2 h / 0 - 80 °C / Inert atmosphere 7.1: hydroxylamine hydrochloride; pyridine / tetrahydrofuran / 12 h / 70 °C 8.1: acetic anhydride / tetrahydrofuran / 24 h / 70 °C 9.1: hydrogen; palladium 10% on activated carbon / methanol; tetrahydrofuran / 48 h / 40 °C 10.1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 12 h / 20 °C 11.1: sodium hydroxide; water / methanol / 2 h / 20 °C 12.1: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

1-(3-benzoyloxypropyl)-5-(2-nitropropyl)-2,3-dihydroindole (350797-54-5) → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: trichlorophosphate / 1 h / 0 °C / Inert atmosphere 1.2: 2 h / 0 - 80 °C / Inert atmosphere 2.1: hydroxylamine hydrochloride; pyridine / tetrahydrofuran / 12 h / 70 °C 3.1: acetic anhydride / tetrahydrofuran / 24 h / 70 °C 4.1: hydrogen; palladium 10% on activated carbon / methanol; tetrahydrofuran / 48 h / 40 °C 5.1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 12 h / 20 °C 6.1: sodium hydroxide; water / methanol / 2 h / 20 °C 7.1: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

1-(3-benzoyloxypropyl)-7-formyl-5-(2-nitropropyl)-2,3-dihydroindole (350797-55-6) → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions

Yield

Multi-step reaction with 6 steps 1: hydroxylamine hydrochloride; pyridine / tetrahydrofuran / 12 h / 70 °C 2: acetic anhydride / tetrahydrofuran / 24 h / 70 °C 3: hydrogen; palladium 10% on activated carbon / methanol; tetrahydrofuran / 48 h / 40 °C 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 12 h / 20 °C 5: sodium hydroxide; water / methanol / 2 h / 20 °C 6: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

1-(3-benzoyloxypropyl)-7-cyano-5-(2-nitropropyl)-2,3-dihydroindole (350797-56-7) → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogen; palladium 10% on activated carbon / methanol; tetrahydrofuran / 48 h / 40 °C 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 12 h / 20 °C 3: sodium hydroxide; water / methanol / 2 h / 20 °C 4: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

Benzoic acid-3-[7-cyano-5(R)-(2-{2-[2-(2,2,2-trifluoro-ethoxy)-phenoxy]-ethylamino}-propyl)-2,3-dihydro-indol-1-yl]-propyl ester → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide; water / methanol / 2 h / 20 °C 2: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

5-(2-aminopropyl)-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-cyano-1H-indole (1338365-54-0) → 1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 12 h / 20 °C 2: sodium hydroxide; water / methanol / 2 h / 20 °C 3: sodium hydroxide; water; dihydrogen peroxide / dimethyl sulfoxide / 0 - 25 °C View Scheme

1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide (160970-64-9) → silodosin (160970-54-7)

Conditions	Yield
In ethyl acetate at 15 - 55℃;	7.2g

Upstream product

• 350797-52-3 1-(3-benzoyloxypropyl)-5-formyl-2,3-dihydroindole 
• 350797-53-4 1-(3-benzoyloxypropyl)-5-(2-nitro-1-propenyl)-2,3-dihydroindole 
• 496-15-1 1-indoline 
• 350797-54-5 1-(3-benzoyloxypropyl)-5-(2-nitropropyl)-2,3-dihydroindole 
• 350797-55-6 1-(3-benzoyloxypropyl)-7-formyl-5-(2-nitropropyl)-2,3-dihydroindole 
• 350797-56-7 1-(3-benzoyloxypropyl)-7-cyano-5-(2-nitropropyl)-2,3-dihydroindole 
• 1338365-54-0 5-(2-aminopropyl)-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-cyano-1H-indole 

Downstream Products

• 160970-54-7 silodosin 

Relevant articles and documents

Design, Synthesis, and Biological Evaluation of Indoline and Indole Derivatives as Potent and Selective α1A-Adrenoceptor Antagonists

A series of indoline and indole derivatives were designed, synthesized, and evaluated as selective α1A-adrenergic receptor (α1A-AR) antagonists for the treatment of benign prostatic hyperplasia (BPH). In this study, two highly selective and potent α1A-AR antagonists, compounds (R)-14r (IC50 = 2.7 nM, α1B/α1A = 640.1, α1D/α1A = 408.2) and (R)-23l (IC50 = 1.9 nM, α1B/α1A = 1506, α1D/α1A = 249.6), which exhibited similar activities and better selectivities in cell-based calcium assays as compared with the marketed drug silodosin (IC50 = 1.9 nM, α1B/α1A = 285.9, α1D/α1A = 14.4), were identified. In the functional assays with isolated rat tissues, compounds (R)-14r and (R)-23l also showed high potency and uroselectivity. Most importantly, (R)-14r and (R)-23l can significantly decrease the micturition frequency and increase the mean voided volume of the BPH rats in a dose-dependent manner, making them worthy of further investigation for the development of anti-BPH agents.