160129-45-3

Basic information

• Product Name: 7-CHLORO-1,2,3,4-TETRAHYDRO-BENZO[B]AZEPIN-5-ONE
• Synonyms: 7-CHLORO-1,2,3,4-TETRAHYDRO-BENZO[B]AZEPIN-5-ONE;7-chloro-1, 2, 3, 4-benzo [b] AZA Zhuo-5-ketone;7-Chloro-1,2,3,4-tetrahydro-5H-1-benzozepin-5-one;5H-1-Benzazepin-5-one,7-chloro-1,2,3,4-tetrahydro-;7-Chlorobenzo[b]azepan-5-one;7-chloro-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one;7-Chloro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one;7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one
• CAS NO: 160129-45-3
• Molecular Formula: C₁₀H₁₀ClNO
• Molecular Weight: 195.65
• EINECS: 1312995-182-4
• Product Categories: Building Blocks/Intermediates;Tolvaptan intermediate
• Mol File: 160129-45-3.mol
• Article Data: 10

Chemical Properties

• Melting Point: 103.0 to 107.0 °C
• Boiling Point: 356.5 °C at 760 mmHg
• Flash Point: 169.4 °C
• Appearance: /
• Density: 1.234 g/cm³
• Vapor Pressure: 2.9E-05mmHg at 25°C
• Refractive Index: 1.562
• Storage Temp.: 2-8°C(protect from light)
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 2.36±0.20(Predicted)
• CAS DataBase Reference: 7-CHLORO-1,2,3,4-TETRAHYDRO-BENZO[B]AZEPIN-5-ONE(CAS DataBase Reference)
• NIST Chemistry Reference: 7-CHLORO-1,2,3,4-TETRAHYDRO-BENZO[B]AZEPIN-5-ONE(160129-45-3)
• EPA Substance Registry System: 7-CHLORO-1,2,3,4-TETRAHYDRO-BENZO[B]AZEPIN-5-ONE(160129-45-3)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• Hazardous Substances Data: 160129-45-3(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 160129-45-3 differently. You can refer to the following data:
1. 7-Chloro-1,2,3,4-tetrahydrobenzo[b]azepin-5-one is an intermediate in the synthesis of Tolvaptan (T536650) (OPC-41061), an orally active nonpeptide arginine vasopressin V2 receptor antagonist
2. 7-Chloro-1,2,3,4-tetrahydrobenzo[b]azepin-5-one is an intermediate in the synthesis of 7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5 -tetrahydro-1H-1-benzazepine (OPC-41061) , an orally active nonpeptide arginine vasopressin V2 receptor antagonist

InChI:InChI=1/C10H10ClNO/c11-7-3-4-9-8(6-7)10(13)2-1-5-12-9/h3-4,6,12H,1-2,5H2

Synthetic route

methyl 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carboxylate → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
With hydrogenchloride In water at 50℃; for 3h; Reagent/catalyst; Temperature;	90.3%

7-chloro-1-(4-methylbenzenesulfonyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (193686-76-9) → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
Stage #1: 7-chloro-1-(4-methylbenzenesulfonyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one With sulfuric acid In water at 0 - 10℃; for 2.5h; Stage #2: With sodium hydroxide In water	89%
With PPA at 80 - 100℃; for 1.5h; detosylation;	81%
With PPA at 100℃;

ethyl 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carboxylate → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
With formic acid at 150℃; for 3h;	88.1%

1-allyl-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzoazepine → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
With 1,3-dimethylbarbituric acid; palladium diacetate; triphenylphosphine In dichloromethane at 35℃; for 8h; Inert atmosphere;	88%

methyl 7-chloro-5-oxo-1-p-toluenesulfonyl-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carboxylate → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
With sulfuric acid at 50℃; for 2h; Temperature;	84.6%
Multi-step reaction with 2 steps 1: sulfuric acid / 2 h / 40 °C 2: hydrogenchloride / water / 3 h / 50 °C View Scheme

4-chlorobenzenesulfonyl chloride (5202-89-1) → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 85 percent / pyridine / 20 °C 2.1: 94 percent / K2CO3 / dimethylformamide / 4 h / 120 °C 3.1: t-BuOK / toluene / 0.5 h / Heating 3.2: 60 percent / conc. HCl / acetic acid / 5 h / Heating 4.1: 81 percent / polyphosphoric acid / 1.5 h / 80 - 100 °C View Scheme

5-chloro-2-nitrobenzoic acid (2516-95-2) → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: 100 percent / K2CO3 / acetone / 0.5 h / Heating 2.1: SnCl2*2H2O; conc. HCl / ethanol / 20 °C 3.1: 85 percent / pyridine / 20 °C 4.1: 94 percent / K2CO3 / dimethylformamide / 4 h / 120 °C 5.1: t-BuOK / toluene / 0.5 h / Heating 5.2: 60 percent / conc. HCl / acetic acid / 5 h / Heating 6.1: 81 percent / polyphosphoric acid / 1.5 h / 80 - 100 °C View Scheme

methyl 5-chloro-2-nitrobenzoate (51282-49-6) → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: SnCl2*2H2O; conc. HCl / ethanol / 20 °C 2.1: 85 percent / pyridine / 20 °C 3.1: 94 percent / K2CO3 / dimethylformamide / 4 h / 120 °C 4.1: t-BuOK / toluene / 0.5 h / Heating 4.2: 60 percent / conc. HCl / acetic acid / 5 h / Heating 5.1: 81 percent / polyphosphoric acid / 1.5 h / 80 - 100 °C View Scheme

N-p-toluenesulfonyl-5-chloro-anthranilic acid methyl ester (247237-38-3) → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 94 percent / K2CO3 / dimethylformamide / 4 h / 120 °C 2.1: t-BuOK / toluene / 0.5 h / Heating 2.2: 60 percent / conc. HCl / acetic acid / 5 h / Heating 3.1: 81 percent / polyphosphoric acid / 1.5 h / 80 - 100 °C View Scheme

methyl 5-chloro-2-[N-(3-ethoxycarbonyl)propyl-N-p-toluenesulfonyl]aminobenzoate (247237-43-0) → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: t-BuOK / toluene / 0.5 h / Heating 1.2: 60 percent / conc. HCl / acetic acid / 5 h / Heating 2.1: 81 percent / polyphosphoric acid / 1.5 h / 80 - 100 °C View Scheme

ethyl 7-chloro-5-oxo-1-p-toluenesulfonyl-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carboxylate → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
Stage #1: ethyl 7-chloro-5-oxo-1-p-toluenesulfonyl-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carboxylate With sulfuric acid In water at 75℃; for 2h; Stage #2: With sodium hydroxide In water pH=7.5 - 8;
Stage #1: ethyl 7-chloro-5-oxo-1-p-toluenesulfonyl-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carboxylate With sulfuric acid; water at 75℃; for 2h; Stage #2: With sodium hydroxide In water at 20℃; pH=7.5 - 8.0;	160 g

5-chloro-2-(diallylamino)benzaldehyde → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 5,5-dimethyl-1,3-cyclohexadiene / 18 h / 175 °C / Sealed tube 2: sulfuric acid / water / 11 h / 90 °C 3: 1,3-dimethylbarbituric acid; palladium diacetate; triphenylphosphine / dichloromethane / 8 h / 35 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: 5,5-dimethyl-1,3-cyclohexadiene / 18 h / 175 °C 2.1: sulfuric acid / water / 11 h / 90 °C 3.1: 1,3-dimethylbarbituric acid; palladium diacetate; triphenylphosphine / dichloromethane / 8 h / Inert atmosphere; Reflux 3.2: Cooling with ice 4.1: sodium hydrogencarbonate / water View Scheme

1-allyl-7-chloro-2,3,4,5-tetrahydro-1H-2,5-epoxybenzo[b]azepine → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid / water / 11 h / 90 °C 2: 1,3-dimethylbarbituric acid; palladium diacetate; triphenylphosphine / dichloromethane / 8 h / 35 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: sulfuric acid / water / 11 h / 90 °C 2.1: 1,3-dimethylbarbituric acid; palladium diacetate; triphenylphosphine / dichloromethane / 8 h / Inert atmosphere; Reflux 2.2: Cooling with ice 3.1: sodium hydrogencarbonate / water View Scheme

5-chloro-2-fluorobenzaldehyde (96515-79-6) → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium carbonate / water; acetonitrile / 72 h / Reflux 2: 5,5-dimethyl-1,3-cyclohexadiene / 18 h / 175 °C / Sealed tube 3: sulfuric acid / water / 11 h / 90 °C 4: 1,3-dimethylbarbituric acid; palladium diacetate; triphenylphosphine / dichloromethane / 8 h / 35 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / acetonitrile; water / 60 h / Reflux 2.1: 5,5-dimethyl-1,3-cyclohexadiene / 18 h / 175 °C 3.1: sulfuric acid / water / 11 h / 90 °C 4.1: 1,3-dimethylbarbituric acid; palladium diacetate; triphenylphosphine / dichloromethane / 8 h / Inert atmosphere; Reflux 4.2: Cooling with ice 5.1: sodium hydrogencarbonate / water View Scheme

7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine hydrochloride → 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3)

Conditions	Yield
With sodium hydrogencarbonate In water	745 mg

2-methyl-4-nitrobenzoyl chloride (30459-70-2) + 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 1-(4-nitro-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137982-91-3)

Conditions	Yield
Stage #1: 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one With magnesium hydroxide In acetonitrile at 10℃; for 0.5h; Stage #2: 2-methyl-4-nitrobenzoyl chloride In acetonitrile for 5h;	95%
With sodium hydroxide In acetonitrile at 20℃; for 1h;	73%
With triethylamine In dichloromethane at 20℃; for 2h; Acylation;	32%

carbon monoxide (201230-82-2) + 2-bromo-5-nitrotoluene (7149-70-4) + 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 1-(4-nitro-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137982-91-3)

Conditions	Yield
With palladium diacetate; potassium carbonate; triphenylphosphine In water; N,N-dimethyl-formamide at 120℃; under 22502.3 Torr; for 8h; Temperature; Pressure; Autoclave;	92.7%

2-methoxy-4-nitrobenzoyl chloride (39787-83-2) + 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 7-chloro-1-(2-methoxy-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (247237-91-8)

Conditions	Yield
With pyridine Acylation;	92%

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) + 2-bromoethanol (540-51-2) → C12H14ClNO2

Conditions	Yield
With triethylamine In ethanol for 15h; Reflux;	90.4%

3-chloro-4-nitro-benzoic acid chloride (55737-29-6) + 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 7-chloro-1-(3-chloro-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (247237-89-4)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h; Acylation;	89%

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) + 1-bromo-3-propanol (627-18-9) → C13H16ClNO2

Conditions	Yield
With potassium hydrogencarbonate In N,N-dimethyl-formamide for 12h; Reflux;	87.9%

carbon monoxide (201230-82-2) + 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) + 2-bromo-5-(2-methylbenzoylamino)toluene (317374-07-5) → MOP-21826 (137973-76-3)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene; triphenylphosphine; palladium diacetate In N,N-dimethyl-formamide at 125℃; for 3h;	85%
With 1,8-diazabicyclo[5.4.0]undec-7-ene; palladium diacetate; triphenylphosphine In N,N-dimethyl-formamide at 20 - 125℃; for 3h;	85%

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 7-chloro-2,3,4,5-tetrahydro-1H-benzo[b]azepine (313673-94-8)

Conditions	Yield
With hydrazine hydrate; potassium hydroxide In 1,2-dimethoxyethane at 160℃; for 4h;	77%

carbon monoxide (201230-82-2) + 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) + 2-bromo-5-(2-methylbenzoylamino)toluene (317374-07-5) → MOP-21826 (137973-76-3) + 2-methyl-4-(2-methylbenzoylamino)benzoic acid (317374-08-6)

Conditions	Yield
With cesium acetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; triphenylphosphine; palladium diacetate In N,N-dimethyl-formamide Heating;	A n/a B 75%

4-nitro-benzoyl chloride (122-04-3) + 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 7-chloro-1-(4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137984-92-0)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h; Acylation;	57%

2-chloro-4-nitrobenzoyl chloride (7073-36-1) + 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 7-chloro-1-(2-chloro-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137977-93-6)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h; Acylation;	57%

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → (±)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-ol

Conditions	Yield
With C19H29N4Ru(1+)*C24H20B(1-); potassium hydroxide In isopropyl alcohol at 80℃; for 2h; Inert atmosphere; Schlenk technique;	56%

3-methoxy-4-nitrobenzoic acid chloride (67579-92-4) + 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 7-chloro-1-(3-methoxy-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137982-83-3)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h; Acylation;	31%

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → tolvaptan (150683-30-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 32 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 39 percent / SnCl2*2H2O; conc. HCl / ethanol / 20 °C 3: 53 percent / Et3N / CH2Cl2 / 1.5 h / 20 °C 4: 30 percent / NaBH4 / methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydrogencarbonate / dichloromethane; water / pH 7 - 8 2.1: tin(ll) chloride / methanol / 16 h / 20 °C 3.1: sodium hydrogencarbonate / dichloromethane / 0 - 5 °C / pH 7 - 8 4.1: sodium tetrahydroborate; methanol / 1 h / 20 °C 4.2: pH 6 - 7 View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydrogencarbonate / water; dichloromethane / 0 - 5 °C / pH 7.0 - 8.0 2.1: tin(IV) chloride / methanol / 16 h / 20 °C 3.1: sodium hydrogencarbonate / water; dichloromethane / 0 - 5 °C / pH 7.0 - 8.0 4.1: sodium tetrahydroborate / methanol / 1 h / 20 °C 4.2: pH 6.0 - 7.0 View Scheme
Multi-step reaction with 4 steps 1: potassium carbonate; triphenylphosphine; palladium diacetate / N,N-dimethyl-formamide; water / 8 h / 120 °C / 22502.3 Torr / Autoclave 2: iron; ammonium chloride / water; methanol / 6 h / 35 - 40 °C 3: pyridine / dichloromethane / 2 h / 0 - 10 °C 4: sodium tetrahydroborate; methanol / 1 h / 15 - 30 °C View Scheme
Multi-step reaction with 4 steps 1.1: magnesium hydroxide / acetonitrile / 0.5 h / 10 °C 1.2: 5 h 2.1: methanol; tin(II) chloride dihdyrate / 23 h / 10 °C 3.1: magnesium hydroxide / dichloromethane; water / 0.5 h / 10 °C 3.2: 3 h 4.1: sodium tetrahydroborate; methanol / 1 h View Scheme

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 1-(4-aminobenzoyl)-7-chloro-5-methoxy-2,3,4,5-tetrahydro-1H-1-benzazepine (247237-83-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 57 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 99 percent / NaBH4 / methanol / 1 h / 20 °C 3: 71 percent / NaH / dimethylformamide / 1 h / 20 °C 4: 93 percent / SnCl2*2H2O; conc. HCl / ethanol / 20 °C View Scheme

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 7-chloro-5-methoxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine (247237-79-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 57 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 99 percent / NaBH4 / methanol / 1 h / 20 °C 3: 71 percent / NaH / dimethylformamide / 1 h / 20 °C View Scheme

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 1-(4-aminobenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137984-95-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 57 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 66 percent / conc. HCl; H2 / PtO2 / acetic acid / 760 Torr View Scheme

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 7-chloro-5-hydroxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine (247237-78-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 57 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 99 percent / NaBH4 / methanol / 1 h / 20 °C View Scheme

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137977-97-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 32 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 39 percent / SnCl2*2H2O; conc. HCl / ethanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / dichloromethane; water / pH 7 - 8 2: tin(ll) chloride / methanol / 16 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water; dichloromethane / 0 - 5 °C / pH 7.0 - 8.0 2: tin(IV) chloride / methanol / 16 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate; triphenylphosphine; palladium diacetate / N,N-dimethyl-formamide; water / 8 h / 120 °C / 22502.3 Torr / Autoclave 2: iron; ammonium chloride / water; methanol / 6 h / 35 - 40 °C View Scheme
Multi-step reaction with 2 steps 1.1: magnesium hydroxide / acetonitrile / 0.5 h / 10 °C 1.2: 5 h 2.1: methanol; tin(II) chloride dihdyrate / 23 h / 10 °C View Scheme

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 1-(4-amino-3-chlorobenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (247237-93-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 89 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 86 percent / SnCl2*2H2O; conc. HCl / ethanol / 20 °C View Scheme

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 1-(4-amino-2-methoxybenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137976-75-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 92 percent / pyridine 2: 89 percent / SnCl2*2H2O; conc. HCl / ethanol / 20 °C View Scheme

7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one (160129-45-3) → 1-(4-amino-3-methoxybenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137982-87-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 31 percent / Et3N / CH2Cl2 / 2 h / 20 °C 2: 83 percent / conc. HCl; H2 / PtO2 / acetic acid / 760 Torr View Scheme

Upstream product

• 51282-49-6 methyl 5-chloro-2-nitrobenzoate 
• 1133419-00-7 ethyl 7-chloro-5-oxo-1-p-toluenesulfonyl-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carboxylate 
• 1127-74-8 1,2,3,4-tetrahydro-5H-benzo[b] azepin-5-one 
• 792931-76-1 ethyl 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carboxylate 
• 96515-79-6 5-chloro-2-fluorobenzaldehyde 
• 247237-43-0 methyl 5-chloro-2-[N-(3-ethoxycarbonyl)propyl-N-p-toluenesulfonyl]aminobenzoate 
• 247237-38-3 N-p-toluenesulfonyl-5-chloro-anthranilic acid methyl ester 
• 2516-95-2 5-chloro-2-nitrobenzoic acid 
• 5202-89-1 4-chlorobenzenesulfonyl chloride 
• 193686-76-9 7-chloro-1-(4-methylbenzenesulfonyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one 

Downstream Products

• 137982-83-3 7-chloro-1-(3-methoxy-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 247237-89-4 7-chloro-1-(3-chloro-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 247237-91-8 7-chloro-1-(2-methoxy-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 137977-93-6 7-chloro-1-(2-chloro-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 137973-76-3 MOP-21826 
• 313673-94-8 7-chloro-2,3,4,5-tetrahydro-1H-benzo[b]azepine 
• 137982-91-3 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 154890-90-1 5-(N-allylamino)-7-chloro-1-[4-[(2-methylbenzoyl)amino]benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 247237-98-5 7-chloro-1-[3-chloro-4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 137978-52-0 7-chloro-1-[3-methoxy-4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 137974-15-3 7-chloro-1-[2-methoxy-4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 137973-86-5 7-chloro-1-[2-chloro-4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 

Relevant articles and documents

Halogenated method of aromatic compound

The invention belongs to the field of organic synthesis, and particularly relates to synthesis of aromatic halogens, in particular to arylamine. The invention discloses a synthesis method of a corresponding ortho-halogenated product from aromatic compounds such as carbazole and phenol. The method comprises the following steps: adding a metal sulfonate salt catalyst, aromatic amine, carbazole, phenol and other hydrogen - heteroatom-containing aromatic compound reaction substrates, a halogenation reagent and a reaction solvent at a specific reaction temperature. After the drying agent is dried, the yield of the reaction product and the nuclear magnetic characterization determining structure are determined by column chromatography. The reaction product yield is determined by gas chromatography. By adopting the method, under the cheap metal salt catalyst, a plurality of ortho-substituted brominated and chloro products can be obtained with moderate to excellent yield.

A the request cuts down the Pu Tanzania intermediate and its preparation method

The invention discloses a 7-chloro-5-oxo-2, 3, 4, 5-tetrahydro-1H-1-benzoazepine carboxylic ester compound, its preparation method, and a method of utilizing the compound to prepare another tolvaptan intermediate 7-chloro-5-oxo-2, 3, 4, 5-tetrahydro-1H-1-benzoazepine. The 7-chloro-5-oxo-2, 3, 4, 5-tetrahydro-1H-1-benzoazepine prepared by the method provided in the invention has a high yield, and can be prepared by a one-pot process, thus greatly simplifying the reaction operation. Also, the used materials and reagents are cheap and commercially available, the reaction is mild and environment-friendly, so that the method is suitable for large-scale production.

A Cascade of acid-promoted c-o bond cleavage and redox reactions: From oxa-bridged benzazepines to benzazepinones

A sequence of C-O bond cleavage and redox reactions in oxa-bridged azepines was realized under acid promoted conditions. This protocol provides an atom-economical and straightforward approach to access benzo[b]azepin-5(2H)-ones in high yields. The formal synthesis of tolvaptan was achieved by exploiting this new transformation.