230615-52-8

Basic information

• Product Name: 2,3,4,5-TETRAHYDRO-1H-1,5-METHANO-3-BENZAZEPINE HYDROCHLORIDE
• Synonyms: 2,3,4,5-TETRAHYDRO-1H-1,5-METHANO-3-BENZAZEPINE HYDROCHLORIDE;1,5-Methano-1H-3-benzazepine, 2,3,4,5-tetrahydro-, hydrochloride;2,3,4,5-Tetrahydro-1,5-methano-1H-3-benzazepine hydrochloride;hydrochloride (1:1);2,3,4,5-tetrahydro-1H-1,5-methanobenzo[d]azepine hydrochloride
• CAS NO: 230615-52-8
• Molecular Formula: C₁₁H₁₃N*ClH
• Molecular Weight: 195.69
• Mol File: 230615-52-8.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 277.9 °C at 760 mmHg
• Flash Point: 128.9 °C
• Appearance: /
• Vapor Pressure: 0.00439mmHg at 25°C
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Chloroform (Slightly, Heated), Methanol (Slightly)
• CAS DataBase Reference: 2,3,4,5-TETRAHYDRO-1H-1,5-METHANO-3-BENZAZEPINE HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 2,3,4,5-TETRAHYDRO-1H-1,5-METHANO-3-BENZAZEPINE HYDROCHLORIDE(230615-52-8)
• EPA Substance Registry System: 2,3,4,5-TETRAHYDRO-1H-1,5-METHANO-3-BENZAZEPINE HYDROCHLORIDE(230615-52-8)

Safety Data

• Hazardous Substances Data: 230615-52-8(Hazardous Substances Data)

Usage

Uses

2,3,4,5-Tetrahydro-1H-1,5-methano-3-benzazepine Hydrochloride is used in the preparation of the main band impurity of Varenicline (V098490), a nicotinic α4β2 acetylcholine receptor partial agonist. Aid in smoking cessation.

InChI:InChI=1/C11H13N.ClH/c1-2-4-11-9-5-8(6-12-7-9)10(11)3-1;/h1-4,8-9,12H,5-7H2;1H

Synthetic route

10-Aza-tricyclo[6.3.1.02.7]dodeca-2(7),3,5-triene (69718-72-5) → 2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8)

Conditions	Yield
With hydrogenchloride In methanol at 0 - 5℃; Solvent;	96%

3-benzyl-2,3,4,5-tetrahydro-1,5-methano-1H-3-benzazepine (230615-48-2) → 2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8)

Conditions	Yield
With hydrogenchloride; hydrogen; palladium(II) hydroxide In methanol at 20 - 40℃; under 3677.86 - 4413.43 Torr;	89.24%
Stage #1: 3-benzyl-2,3,4,5-tetrahydro-1,5-methano-1H-3-benzazepine With ammonium formate; palladium(II) hydroxide In methanol for 0.5h; Inert atmosphere of nitrogen; Reflux; Stage #2: With hydrogenchloride In ethyl acetate at 0 - 5℃; for 1h; pH=1 - 2;

2-indanone (615-13-4) → 2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: acetic acid; bromine / 2 h / 25 °C / Cooling with ice 2.1: ethanol; water / 5 h / 20 °C 3.1: potassium hydroxide; water / ethanol / 4 h / 75 °C 4.1: acetic anhydride / 5 h / 100 °C 4.2: 3 h / 75 °C 5.1: sodium tetrahydroborate / tetrahydrofuran / 6 h / 20 °C / Cooling with ice 6.1: hydrogenchloride / methanol / 0 - 5 °C View Scheme

1,3-dibromo-indan-2-one (39094-23-0) → 2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: ethanol; water / 5 h / 20 °C 2.1: potassium hydroxide; water / ethanol / 4 h / 75 °C 3.1: acetic anhydride / 5 h / 100 °C 3.2: 3 h / 75 °C 4.1: sodium tetrahydroborate / tetrahydrofuran / 6 h / 20 °C / Cooling with ice 5.1: hydrogenchloride / methanol / 0 - 5 °C View Scheme

C11H6N2O → 2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium hydroxide; water / ethanol / 4 h / 75 °C 2.1: acetic anhydride / 5 h / 100 °C 2.2: 3 h / 75 °C 3.1: sodium tetrahydroborate / tetrahydrofuran / 6 h / 20 °C / Cooling with ice 4.1: hydrogenchloride / methanol / 0 - 5 °C View Scheme

C11H8O5 → 2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: acetic anhydride / 5 h / 100 °C 1.2: 3 h / 75 °C 2.1: sodium tetrahydroborate / tetrahydrofuran / 6 h / 20 °C / Cooling with ice 3.1: hydrogenchloride / methanol / 0 - 5 °C View Scheme

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) + 2-chloro-5-(chloromethyl)pyridine (70258-18-3) → C17H17ClN2

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In acetone for 6h; pH=10; Reflux;	78.2%

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) + C11H7BrF7NO → C22H19F7N2O

Conditions	Yield
With potassium carbonate; sodium iodide In acetonitrile at 60℃; for 18h;	70%

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) + 4-methoxy-3-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride (1184086-20-1) → 2-methoxy-5-((1,2,4,5-tetrahydro-3H-1,5-methanobenzo[d]azepin-3-yl)sulfonyl)aniline

Conditions	Yield
Stage #1: 2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride; 4-methoxy-3-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride With dmap; triethylamine In dichloromethane for 1h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol; water for 16h; Inert atmosphere; Reflux;	65%

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) + trifluoroacetic anhydride (407-25-0) → 1-(10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone (230615-51-7)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; Product distribution / selectivity;
With pyridine In dichloromethane at 0℃; for 0.166667h;
With pyridine In dichloromethane

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) → (+/-)-2,2,2-trifluoro-1-(4-nitro-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-10-yl)-ethanone (230615-53-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / dichloromethane 2: trifluorormethanesulfonic acid; nitric acid / dichloromethane View Scheme

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) → 1-(4-Iodo-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone (230615-77-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine / dichloromethane 2: trifluorormethanesulfonic acid; nitric acid / dichloromethane 3: palladium-carbon / methanol 4: potassium iodide / sulfuric acid; water View Scheme

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) → 1-(4-amino-10-aza-tricyclo[6.3.1.02,7]dodeca-2,4,6-trien-10-yl)-2,2,2-trifluoro-ethanone (230615-56-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / dichloromethane 2: trifluorormethanesulfonic acid; nitric acid / dichloromethane 3: palladium-carbon / methanol View Scheme

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) → 4-Acetyl-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-10-carboxylic acid tert-butyl ester (230615-81-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / dichloromethane 2: acetyl chloride 3: 1,4-dioxane; methanol; water View Scheme

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) → 1-(4-Acetyl-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone (230615-80-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / dichloromethane 2: acetyl chloride View Scheme

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) → N-(10-Trifluorothioacetyl-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-4-yl)-thioacetamide (357425-94-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: pyridine / dichloromethane 2: trifluorormethanesulfonic acid; nitric acid / dichloromethane 3: palladium-carbon / methanol 4: triethylamine / dichloromethane 5: toluene View Scheme

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) → N-(10-Trifluoroacetyl-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-4-yl)-acetamide (230615-57-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine / dichloromethane 2: trifluorormethanesulfonic acid; nitric acid / dichloromethane 3: palladium-carbon / methanol 4: triethylamine / dichloromethane View Scheme

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) → 1-(10-AZATRICYCLO[6.3.1.02,7]DODECA-2(7),3,5-TRIEN-4-YL)-1-ETHANONE HYDROCHLORIDE (230615-31-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine / dichloromethane 2: acetyl chloride 3: 1,4-dioxane; methanol; water 4: methanol View Scheme

2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine hydrochloride (230615-52-8) → N1-[10-AZATRICYCLO[6.3.1.02,7]DODECA-2(7),3,5-TRIEN-4-YL]-ACETAMIDE HYDROCHLORIDE (230615-06-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: pyridine / dichloromethane 2: trifluorormethanesulfonic acid; nitric acid / dichloromethane 3: palladium-carbon / methanol 4: triethylamine / dichloromethane 5: sodium carbonate / methanol; water View Scheme

Upstream product

• 69718-72-5 10-Aza-tricyclo[6.3.1.02.7]dodeca-2⁽⁷⁾,3,5-triene 
• 39094-23-0 1,3-dibromo-indan-2-one 
• 615-13-4 2-indanone 
• 230615-48-2 3-benzyl-2,3,4,5-tetrahydro-1,5-methano-1H-3-benzazepine 

Downstream Products

• 230615-53-9 1-(4-nitro-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone 
• 230615-51-7 1-(10-aza-tricyclo[6.3.1.0^2,7]dodeca-2⁽⁷⁾,3,5-trien-10-yl)-2,2,2-trifluoro-ethanone 

Relevant articles and documents

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