312753-53-0

Basic information

• Product Name: 5,6-Diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride
• Synonyms: 1H-Inden-2-aMine,5,6-diethyl-2,3-dihydro-,hydrochloride (1:1);5,6-Diethyl-2,3-dihydro-1H-inden-2-aMino Hydrochloride;5,6-Diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride 312753-53-0;1H-Inden-2-amine,5,6-diethyl-2,3-dihydro-, hydrochloride;5-ethyl-2,3-dihydro-1H-inden-2-amine;5,6-Diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride;5,6-diethyl-2,3-dihydro-1H-inden-2-amine;Indacaterol Intermediate 1
• CAS NO: 312753-53-0
• Molecular Formula: C₁₃H₁₉N*ClH
• Molecular Weight: 225.76
• EINECS: 1308068-626-2
• Product Categories: Intermediate of Indacaterol
• Mol File: 312753-53-0.mol
• Article Data: 6

Chemical Properties

• Melting Point: >250 ºC
• Boiling Point: 285.2 °C at 760 mmHg
• Flash Point: 127.6 °C
• Appearance: /
• Vapor Pressure: 0.00285mmHg at 25°C
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 5,6-Diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 5,6-Diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride(312753-53-0)
• EPA Substance Registry System: 5,6-Diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride(312753-53-0)

Safety Data

• Hazardous Substances Data: 312753-53-0(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 312753-53-0 differently. You can refer to the following data:
1. 5,6-Diethyl-2,3-dihydro-1H-inden-2-amine Hydrochloride acts as a reagent in the synthetic preparation of quinolinone compounds and it’s formulations in combination with corticosteroids for treatment of airway disorder.
2. 5,6-Diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride is used as organic synthesis intermediate and pharmaceutical intermediate, mainly used in laboratory research and development process and chemical production process.

Synthesis

Preparation 4-5,6-Diethyl-indan-2-ylamine Hydrochloride 5,6-Diethyl-3-oxime-1H-indene-1,2(3H)-dione (4.5 g) is added to a mixture of acetic acid (150 mL), and concentrated sulphuric acid (4.5 mL). Pd/C5% (1.5 g) is added, the reaction mixture degassed with nitrogen, and hydrogenated for 5 hours. The catalyst is then removed by filtration, the pH brought to pH 10 with 4M NaOH, and the solution extracted with chloroform. The organic phase is dried with magnesium sulphate, and the solvent removed in vacuo. The residue is redisolved in a minimum amount of ether, and HCl saturated ether added. The white precipitate is filtered and dried to yield the HCl salt of 5,6-diethyl-indan-2-ylamine, a compound of formula XVII where R3, R4 and R7 are H, R5 and R6 are each CH3CH2-, R30 is hydrogen and n is 1. 5,6-Diethyl-indan-2-ylamine Hydrochloride.

InChI:InChI=1/C13H19N.ClH/c1-3-9-5-11-7-13(14)8-12(11)6-10(9)4-2;/h5-6,13H,3-4,7-8,14H2,1-2H3;1H

Synthetic route

C15H21NO → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
With hydrogenchloride In water for 10h; Reflux;	92.6%

C13H17N3 → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Stage #1: C13H17N3 With palladium 10% on activated carbon; hydrogen In methanol under 3800.26 Torr; Autoclave; Stage #2: With hydrogenchloride In ethyl acetate	92%

5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
With hydrogenchloride In diethyl ether under 760.051 Torr; Inert atmosphere;	77%
With hydrogenchloride In Isopropyl acetate at 20 - 25℃; for 2.66667h;	70.8 g

5,6-diethyl-3-oxime-1H-indene-1,2(3H)-dione → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Stage #1: 5,6-diethyl-3-oxime-1H-indene-1,2(3H)-dione With sulfuric acid; hydrogen; 5%-palladium/activated carbon In acetic acid for 5h; Stage #2: With sodium hydroxide pH=10; Stage #3: With hydrogenchloride In diethyl ether

N-(5,6-diethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (601487-90-5) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
With hydrogenchloride In Isopropyl acetate; water

N-(2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (193756-44-4) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: aluminum (III) chloride / neat (no solvent) / 0.25 h / 0 - 5 °C 1.2: 255 / 1 h / 0 - 10 °C 2.1: hydrogen; 5%-palladium/activated carbon / ethanol; water / 25 °C / 2250.23 Torr / Inert atmosphere 3.1: aluminum (III) chloride / dichloromethane / 0.75 h / 0 °C 3.2: 1 h / 0 - 5 °C 4.1: palladium 10% on activated carbon / water; ethyl acetate / 0.17 h / 25 °C / 2828.7 Torr / Inert atmosphere 5.1: sodium hydroxide / ethanol / 1.5 h / 78 °C / Inert atmosphere 6.1: hydrogenchloride / Isopropyl acetate / 2.67 h / 20 - 25 °C View Scheme

N-(5-acetyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (601487-87-0) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: hydrogen; 5%-palladium/activated carbon / ethanol; water / 25 °C / 2250.23 Torr / Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 0.75 h / 0 °C 2.2: 1 h / 0 - 5 °C 3.1: palladium 10% on activated carbon / water; ethyl acetate / 0.17 h / 25 °C / 2828.7 Torr / Inert atmosphere 4.1: sodium hydroxide / ethanol / 1.5 h / 78 °C / Inert atmosphere 5.1: hydrogenchloride / Isopropyl acetate / 2.67 h / 20 - 25 °C View Scheme

N-(5-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (601487-88-1) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: aluminum (III) chloride / dichloromethane / 0.75 h / 0 °C 1.2: 1 h / 0 - 5 °C 2.1: palladium 10% on activated carbon / water; ethyl acetate / 0.17 h / 25 °C / 2828.7 Torr / Inert atmosphere 3.1: sodium hydroxide / ethanol / 1.5 h / 78 °C / Inert atmosphere 4.1: hydrogenchloride / Isopropyl acetate / 2.67 h / 20 - 25 °C View Scheme

N-(5-acetyl-6-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (601487-89-2) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: palladium 10% on activated carbon / water; ethyl acetate / 0.17 h / 25 °C / 2828.7 Torr / Inert atmosphere 2: sodium hydroxide / ethanol / 1.5 h / 78 °C / Inert atmosphere 3: hydrogenchloride / Isopropyl acetate / 2.67 h / 20 - 25 °C View Scheme

2,3-dihydro-1H-inden-2-amine (2975-41-9) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: Isopropyl acetate / 3.17 h / 0 - 25 °C 2.1: aluminum (III) chloride / neat (no solvent) / 0.25 h / 0 - 5 °C 2.2: 255 / 1 h / 0 - 10 °C 3.1: hydrogen; 5%-palladium/activated carbon / ethanol; water / 25 °C / 2250.23 Torr / Inert atmosphere 4.1: aluminum (III) chloride / dichloromethane / 0.75 h / 0 °C 4.2: 1 h / 0 - 5 °C 5.1: palladium 10% on activated carbon / water; ethyl acetate / 0.17 h / 25 °C / 2828.7 Torr / Inert atmosphere 6.1: sodium hydroxide / ethanol / 1.5 h / 78 °C / Inert atmosphere 7.1: hydrogenchloride / Isopropyl acetate / 2.67 h / 20 - 25 °C View Scheme
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 2 h / 10 - 20 °C 2.1: aluminum (III) chloride / dichloromethane / 0.33 h / 0 - 10 °C 2.2: 1 h / 10 - 20 °C 3.1: 5%-palladium/activated carbon; hydrogen / ethanol / 6 h / 20 °C 4.1: aluminum (III) chloride / dichloromethane / 0.33 h / 0 - 10 °C 4.2: 1 h / 0 - 10 °C 5.1: 5%-palladium/activated carbon; hydrogen / ethanol / 6 h / 20 °C 6.1: hydrogenchloride / water / 10 h / Reflux View Scheme

N-indan-2-yl-acetamide (13935-80-3) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: aluminum (III) chloride / dichloromethane / 0.33 h / 0 - 10 °C 1.2: 1 h / 10 - 20 °C 2.1: 5%-palladium/activated carbon; hydrogen / ethanol / 6 h / 20 °C 3.1: aluminum (III) chloride / dichloromethane / 0.33 h / 0 - 10 °C 3.2: 1 h / 0 - 10 °C 4.1: 5%-palladium/activated carbon; hydrogen / ethanol / 6 h / 20 °C 5.1: hydrogenchloride / water / 10 h / Reflux View Scheme

N-(5-acetyl-2,3-dihydro-1H-inden-2-yl)acetamide (114149-10-9) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 5%-palladium/activated carbon; hydrogen / ethanol / 6 h / 20 °C 2.1: aluminum (III) chloride / dichloromethane / 0.33 h / 0 - 10 °C 2.2: 1 h / 0 - 10 °C 3.1: 5%-palladium/activated carbon; hydrogen / ethanol / 6 h / 20 °C 4.1: hydrogenchloride / water / 10 h / Reflux View Scheme

N-(5-ethyl-2,3-dihydro-1H-inden-2-yl)acetamide → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / dichloromethane / 0.33 h / 0 - 10 °C 1.2: 1 h / 0 - 10 °C 2.1: 5%-palladium/activated carbon; hydrogen / ethanol / 6 h / 20 °C 3.1: hydrogenchloride / water / 10 h / Reflux View Scheme

indan-2-ol (4254-29-9) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Multi-step reaction with 6 steps 1: 0 - 20 °C 2: bromine; N-Bromosuccinimide / acetonitrile / 20 °C / Darkness 3: tetrahydrofuran / 20 °C / Inert atmosphere 4: pyridine / dichloromethane / 20 °C 5: sodium azide / N,N-dimethyl-formamide / 20 °C 6: palladium 10% on activated carbon; hydrogen / methanol / 3800.26 Torr / Autoclave View Scheme

2-acetoxyindane (4254-31-3) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: bromine; N-Bromosuccinimide / acetonitrile / 20 °C / Darkness 2: tetrahydrofuran / 20 °C / Inert atmosphere 3: pyridine / dichloromethane / 20 °C 4: sodium azide / N,N-dimethyl-formamide / 20 °C 5: palladium 10% on activated carbon; hydrogen / methanol / 3800.26 Torr / Autoclave View Scheme

5,6-dibromoindan-2-ol acetate (862135-55-5) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: tetrahydrofuran / 20 °C / Inert atmosphere 2: pyridine / dichloromethane / 20 °C 3: sodium azide / N,N-dimethyl-formamide / 20 °C 4: palladium 10% on activated carbon; hydrogen / methanol / 3800.26 Torr / Autoclave View Scheme

C13H18O → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / dichloromethane / 20 °C 2: sodium azide / N,N-dimethyl-formamide / 20 °C 3: palladium 10% on activated carbon; hydrogen / methanol / 3800.26 Torr / Autoclave View Scheme

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) + di-tert-butyl dicarbonate (24424-99-5) → 2-tert-butoxycarbonylamino-(5,6-diethyl)indane

Conditions	Yield
With triethylamine In dichloromethane at 0 - 5℃; for 4.5h;	96%

(R)-8-(benzyloxy)-5-(2-bromo-1-((tert-butyldimethylsilyl)oxy)ethyl)quinolin-2(1H)-one (530084-74-3) + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) → (R)-5- [2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-benzyloxy-1H-quinolin-2-one hydrochloride

Conditions	Yield
Stage #1: (R)-8-(benzyloxy)-5-(2-bromo-1-((tert-butyldimethylsilyl)oxy)ethyl)quinolin-2(1H)-one; 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride With sodium hydrogencarbonate In dimethyl sulfoxide at 65 - 125℃; for 6h; Inert atmosphere; Large scale; Stage #2: With hydrogenchloride In ethanol; water at 0 - 72℃; for 27h; Large scale;	71%

(R)-1-carboxymethyl-3-(2-hydroxy-2,2-diphenylacetoxy)-1-azoniabicyclo[2.2.2]octane trifluoroacetate + 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) → (R)-1-[(5,6-diethylindan-2-ylcarbamoyl)methyl]-3-(2-hydroxy-2,2-diphenylacetoxy)-1-azoniabicyclo[2.2.2]octane trifluoroacetate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In DMF (N,N-dimethyl-formamide) at 20℃;

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) + N,N'-(1,1'-(6-chloro-1,3,5-triazine-2,4-diyl)bis(piperidine-4,1-diyl))bis(azanediyl)bis(iminomethylene)bis(3,5-diamino-6-chloropyrazine-2-carboxamide) (1080018-19-4) → N,N'-(1,1'-(6-(dimethylamino)-1,3,5-triazine-2,4-diyl)bis(piperidine-4,1-diyl))bis(azanediyl)bis(aminomethan-1-yl-1-ylidene)bis(3,5-diamino-6-chloropyrazine-2-carboxamide) (1080018-54-7) + N,N'-(1,1'-(6-(5,6-diethyl-2,3-dihydro-1H-inden-2-ylamino)-1,3,5-triazine-2,4-diyl)bis(piperidine-4,1-diyl))bis(azanediyl)bis(aminomethan-1-yl-1-ylidene)bis(3,5-diamino-6-chloropyrazine-2-carboxamide) (1080018-53-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 60 - 70℃; for 44.5h; Microwave irradiation;

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) + C24H28BrNO4 (1585234-56-5) → C36H44N2O4

Conditions	Yield
With sodium carbonate In water at 100℃; for 20h;

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) → C31H34N2O3*BrH

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / water; methanol / 0.5 h 2: butan-1-ol / 3 h / 100 - 110 °C 3: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 0 - 3 °C / Inert atmosphere View Scheme

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) → indacaterol maleate

Conditions

Yield

Multi-step reaction with 6 steps 1: sodium hydroxide / water; methanol / 0.5 h 2: butan-1-ol / 3 h / 100 - 110 °C 3: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 0 - 3 °C / Inert atmosphere 4: potassium carbonate / water; methanol / 1 h 5: acetic acid; palladium 10% on activated carbon; hydrogen / methanol / 6 h / 0 - 8 °C / 750.08 - 1500.15 Torr / Inert atmosphere 6: methanol / 0.5 h / 60 °C View Scheme

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) → 5,6-diethyl-2,3-dihydro-1H-inden-2-amine (312753-70-1)

Conditions	Yield
With sodium hydroxide In methanol; water for 0.5h;

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) → C31H32N2O3*BrH

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water; methanol / 0.5 h 2: butan-1-ol / 3 h / 100 - 110 °C View Scheme

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) → (R)-8-(benzyloxy)-5-[2-[(5,6-diethyl-2,3-dihydro-1H-indole-2-yl)amino]-1-hydroxyethyl]quinolin-2(1H)-one (435273-75-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydroxide / water; methanol / 0.5 h 2: butan-1-ol / 3 h / 100 - 110 °C 3: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 0 - 3 °C / Inert atmosphere 4: potassium carbonate / water; methanol / 1 h View Scheme

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) → indacaterol (312753-06-3)

Conditions

Yield

Multi-step reaction with 5 steps 1: sodium hydroxide / water; methanol / 0.5 h 2: butan-1-ol / 3 h / 100 - 110 °C 3: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 0 - 3 °C / Inert atmosphere 4: potassium carbonate / water; methanol / 1 h 5: acetic acid; palladium 10% on activated carbon; hydrogen / methanol / 6 h / 0 - 8 °C / 750.08 - 1500.15 Torr / Inert atmosphere View Scheme

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) → (R)-5- [2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-benzyloxy-1H-quinolin-2-one hydrochloride

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 4.5 h / 0 - 5 °C 2.1: potassium tert-butylate / N,N-dimethyl-formamide / 4 h / -5 - 20 °C 2.2: 2 h / 20 °C View Scheme

5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride (312753-53-0) → (R)-5- [2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-benzyloxy-1H-quinolin-2-one benzoic acid salt

Conditions	Yield
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 4.5 h / 0 - 5 °C 2.1: potassium tert-butylate / N,N-dimethyl-formamide / 4 h / -5 - 20 °C 2.2: 2 h / 20 °C 3.1: potassium carbonate / ethyl acetate / pH 9 / Cooling with ice 3.2: 2 h View Scheme

Upstream product

• 862135-55-5 5,6-dibromoindan-2-ol acetate 
• 4254-31-3 2-acetoxyindane 
• 4254-29-9 indan-2-ol 
• 114149-10-9 N-(5-acetyl-2,3-dihydro-1H-inden-2-yl)acetamide 
• 13935-80-3 N-indan-2-yl-acetamide 
• 2975-41-9 2,3-dihydro-1H-inden-2-amine 
• 601487-89-2 N-(5-acetyl-6-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide 
• 601487-88-1 N-(5-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide 
• 601487-87-0 N-(5-acetyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide 
• 193756-44-4 N-(2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide 
• 312753-70-1 5,6-diethyl-2,3-dihydro-1H-inden-2-amine 
• 601487-90-5 N-(5,6-diethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide 

Downstream Products

• 312753-06-3 indacaterol 
• 435273-75-9 (R)-8-(benzyloxy)-5-[2-[(5,6-diethyl-2,3-dihydro-1H-indole-2-yl)amino]-1-hydroxyethyl]quinolin-2(1H)-one 
• 312753-70-1 5,6-diethyl-2,3-dihydro-1H-inden-2-amine 
• 753498-25-8 indacaterol maleate 

Relevant articles and documents

Method for preparing 5,6-diethyl-2,3-dihydro-1H-indene-2-amino hydrochloride

The invention relates to a novel synthesis route of a method for preparing 5,6-diethyl-2,3-dihydro-1H-indene-2-amino hydrochloride. 2-indanol is adopted as a raw material, and 5,6-diethyl-2,3-dihydro-1H-indene-2-amino hydrochloride is synthesized with a high yield through seven steps of an acetylation reaction, a substitution reaction, a coupling reaction, a hydroxyl protection reaction, a substitution reaction, a reduction reaction and a salting reaction. The preparation method of the 5,6-diethyl-2,3-dihydro-1H-indene-2-amino hydrochloride, which is provided by the invention, is a preparationmethod which is high in yield, low in cost, friendly to the environment, easy to operate and applicable to industrialization.

The identification of indacaterol as an ultralong-acting inhaled β2-adrenoceptor agonist

Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of β2-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human β2-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference β2-adrenoceptor agonists. Further assessment with an in vitro superfused electrically stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses, which could be rationalized by considering the lipophilicity, potency, and intrinsic efficacy of the compounds. From these studies the 5,6-diethylindan analogue indacaterol 1c was shown to possess a unique profile of combining a rapid onset of action with a long duration of action. Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung, which led to the compound being selected as a development candidate.

Beta2-adrenoceptor agonists

Compounds of formula in free or salt or solvate form, where Ar is a group of formula Y is carbon or nitrogen and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X, n, p, q and r are as defined in the specification, their preparation and their use as pharmaceuticals, particularly for the treatment of obstructive or inflammatory airways diseases.