50492-22-3

Basic information

• Product Name: 4-Perhydroazepinone hydrochloride
• Synonyms: PERHYDROAZEPIN-4-ONEHYDROCHLORIDE;4-PERHYDROAZEPINONE HYDROCHLORIDE;4H-AZEPIN-4-ONE, HEXAHYDRO-, HYDROCHLORIDE;HEXAHYDRO-4H-AZEPIN-4-ONE HCL;HEXAHYDRO-4H-AZEPIN-4-ONE HYDROCHLORIDE;Hexahydro-4-azepin-4-one hydrochloride;4-PerhydroazepinoneHCl;4-PERHYDROAZEPINONE HYDROCHLORIDE HEXAHY
• CAS NO: 50492-22-3
• Molecular Formula: C₆H₁₁NO*ClH
• Molecular Weight: 149.62
• Product Categories: Miscellaneous;pharmacetical;Heterocycles;Miscellaneous Reagents
• Mol File: 50492-22-3.mol
• Article Data: 12

Chemical Properties

• Melting Point: 176-181℃
• Flash Point: 152°(306°F)
• Appearance: /Solid
• Storage Temp.: Inert atmosphere,Room Temperature
• CAS DataBase Reference: 4-Perhydroazepinone hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Perhydroazepinone hydrochloride(50492-22-3)
• EPA Substance Registry System: 4-Perhydroazepinone hydrochloride(50492-22-3)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-41-37/38-20/22
• Safety Statements: 26-36/37/39-36/39
• WGK Germany: 3
• Hazardous Substances Data: 50492-22-3(Hazardous Substances Data)

Usage

Chemical Properties

Yellow Solid

InChI:InChI=1/C6H11NO.ClH/c8-6-2-1-4-7-5-3-6;/h7H,1-5H2;1H

Synthetic route

5-oxo-azepane-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (141642-82-2) → azepan-4-one hydrochloride (50492-22-3)

Conditions	Yield
With hydrogenchloride In water for 15h; Reflux;	100%
With hydrogenchloride for 6h; Heating;	84%
With hydrogenchloride; water for 4h; Heating / reflux;

diazoacetic acid ethyl ester (623-73-4) + N-ethoxycarbonyl-4-piperidone (29976-53-2) → azepan-4-one hydrochloride (50492-22-3)

Conditions	Yield
Stage #1: diazoacetic acid ethyl ester; N-ethoxycarbonyl-4-piperidone With boron trifluoride diethyl etherate In diethyl ether at -35℃; for 1.5h; Stage #2: With hydrogenchloride In water for 6h; Heating / reflux;	88%
Stage #1: diazoacetic acid ethyl ester; N-ethoxycarbonyl-4-piperidone With boron trifluoride diethyl etherate In diethyl ether at -35℃; for 1.5h; Stage #2: With hydrogenchloride; water for 6h; Heating / reflux;	88%

5-oxoazepane-1,4-dicarboxylic acid diethyl ester (19786-58-4) → azepan-4-one hydrochloride (50492-22-3)

Conditions	Yield
With hydrogenchloride for 6h; Heating;

N-ethoxycarbonyl-4-piperidone (29976-53-2) → azepan-4-one hydrochloride (50492-22-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 52.5 g / BF3*Et2O / diethyl ether / 1 h / -30 - -25 °C 2: 4 N HCl / 6 h / Heating View Scheme

tert-butyl 4-oxoazepane-1-carboxylate (188975-88-4) → azepan-4-one hydrochloride (50492-22-3)

Conditions	Yield
With hydrogenchloride In methanol; water at 15℃; for 12h;

1-phenylprop-2-ynyl acetate (16169-88-3, 84681-19-6, 116119-86-9, 116182-55-9) + azepan-4-one hydrochloride (50492-22-3) → (R)-1-(1-phenylprop-2-yn-1-yl)azepan-4-one

Conditions	Yield
With tetrakis(acetonitrile)copper(I) hexafluorophosphate; C32H27N2P; N-ethyl-N,N-diisopropylamine In methanol at -20℃; Inert atmosphere; enantioselective reaction;	96%

azepan-4-one hydrochloride (50492-22-3) + chloroformic acid ethyl ester (541-41-3) → ethyl hexahydro-4-oxo-1H-azepine-1-carboxylate (56515-89-0)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 25℃; for 3h;	95%
With potassium carbonate In water at -5℃; for 4h; Yield given;

azepan-4-one hydrochloride (50492-22-3) + benzyl bromide (100-39-0) → 1-benzylazepan-4-one (1208-75-9)

Conditions	Yield
With potassium carbonate In acetone at 20℃; for 16h;	95%
With potassium carbonate In tetrahydrofuran; water at 50℃; for 3h;	41.5%
With potassium carbonate In tetrahydrofuran; water at 50℃; for 5h;	5 g
With potassium carbonate In tetrahydrofuran; water at 50℃; for 5h;	5 g
With potassium carbonate In tetrahydrofuran; water at 50℃; for 5h;	5 g

azepan-4-one hydrochloride (50492-22-3) + p-toluenesulfonyl chloride (98-59-9) → 1-[(4-methylphenyl)sulfonyl]-4-azepanone (16803-02-4)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	95%
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Reflux;	65%

di-tert-butyl dicarbonate (24424-99-5) + azepan-4-one hydrochloride (50492-22-3) → tert-butyl 4-oxoazepane-1-carboxylate (188975-88-4)

Conditions	Yield
With sodium carbonate In 1,4-dioxane; water at 80℃; for 2h; Product distribution / selectivity;	93%
With sodium hydroxide In methanol; water	93%
With triethylamine In tetrahydrofuran at 60℃; for 6h;	93%

azepan-4-one hydrochloride (50492-22-3) → 5-bromo-azepan-4-one hydrobromide

Conditions	Yield
With hydrogen bromide; bromine; acetic acid at 20℃;	87%
With hydrogen bromide; bromine; acetic acid In water at 20℃;	87%
With hydrogen bromide; bromine; acetic acid	79 mg

azepan-4-one hydrochloride (50492-22-3) + di-tert-butyl dicarbonate (55130-19-3) → tert-butyl 4-oxoazepane-1-carboxylate (188975-88-4)

Conditions	Yield
With sodium hydroxide In water; tert-butyl alcohol at 20℃;	84%

azepan-4-one hydrochloride (50492-22-3) + trifluoroacetic anhydride (407-25-0) → 1-(trifluoroacetyl)-4-azepanone (910325-71-2)

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Reflux;	81%
With triethylamine In dichloromethane at -5 - 20℃; for 18h;

azepan-4-one hydrochloride (50492-22-3) + benzoyl chloride (98-88-4) → 1-benzoylazepan-4-one (15923-40-7)

Conditions	Yield
With triethylamine In dichloromethane for 16h;	76%
With triethylamine In dichloromethane at 0 - 15℃; for 3h;

azepan-4-one hydrochloride (50492-22-3) + benzyl chloroformate (501-53-1) → benzyl 4-oxo-1-azepanecarboxylate (83621-33-4)

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Reflux;	72%

1-amino-1,2,3,4-tetrahydroquinoline (5825-45-6) + azepan-4-one hydrochloride (50492-22-3) → 5,6,9,10,11,12-hexahydro-4H,8H-azepino[4',5':4,5]pyrrolo[3,2,1-ij]quinoline (303799-42-0)

Conditions	Yield
With hydrogenchloride	45%

Upstream product

• 188975-88-4 tert-butyl 4-oxoazepane-1-carboxylate 
• 623-73-4 diazoacetic acid ethyl ester 
• 29976-53-2 N-ethoxycarbonyl-4-piperidone 
• 141642-82-2 5-oxo-azepane-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester 
• 19786-58-4 5-oxoazepane-1,4-dicarboxylic acid diethyl ester 

Downstream Products

• 1116679-91-4 C₁₆H₂₃NO₃S 
• 1186613-83-1 C₁₄H₁₉NO₃S 
• 1186613-84-2 C₁₂H₁₄ClNO₃S 
• 1186613-85-3 C₁₃H₁₇NO₄S 
• 1148136-72-4 1-(4-methoxy-benzyl)-azepan-4-one 
• 1087311-72-5 (S)-2-(dibenzylamino)propyl 4-oxoazepane-1-carboxylate 
• 214613-17-9 1-(4-Fluorophenethyl)-4-(3-methoxyphenylamino)homopiperidine 
• 857677-46-4 1-(trans-3-(4-chlorophenyl)allyl)-perhydroazepin-4-one 
• 143943-98-0 1-<2-(1-hydroxy-1-phenyl)ethyl>-4-(propananilido)perhydroazepine 
• 143943-96-8 1-<2-(1-hydroxy-1-phenyl)ethyl>-4-anilinoperhydroazepine 
• 143943-97-9 1-<2-(1-propoxy-1-phenyl)ethyl>-4-(propananilido)perhydroazepine 
• 143943-99-1 1-carbethoxy-4-(propananilido)perhydroazepine 
• 74134-09-1 1-benzyl-4-anilinoperhydroazepine 
• 74134-06-8 1-(carbethoxy)-4-anilinoperhydroazepine 

Relevant articles and documents

CONJUGATED PROTEINS AND USES THEREOF

Disclosed herein, in certain embodiments, are protein-probe adducts and synthetic ligands that inhibit protein-probe adduct formation, in which the proteins are regulated by NRF2. In some instances, also described herein are protein-binding domains that interact with a probe and/or a ligand described herein, in which the proteins are regulated by NRF2.

NOVEL COMPOUNDS

This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.

1,2,4 -TRIAZOLES AS ALLOSTERIC MODULATORS OF MGLU5 RECEPTOR ACTIVITY FOR THE TREATMENT OF SCHIZOPHRENIA OF DEMENTIA

This invention relates to compounds of formula (I) their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.