116673-95-1

Basic information

• Product Name: 5-Benzyl-3,4-dihydro-3,3-dimethyl-2H-pyrrole
• Synonyms: 5-Benzyl-3,4-dihydro-3,3-dimethyl-2H-pyrrole;2H-Pyrrole,3,4-dihydro-3,3-diMethyl-5-(phenylMethyl)-;5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole;5-benzyl-3,3-dimethyl-2,4-dihydropyrrole
• CAS NO: 116673-95-1
• Molecular Formula: C₁₃H₁₇N
• Molecular Weight: 187.284
• Mol File: 116673-95-1.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 271.509 °C at 760 mmHg
• Flash Point: 109.789 °C
• Appearance: /
• Density: 0.96
• Vapor Pressure: 0.011mmHg at 25°C
• Refractive Index: 1.54
• Storage Temp.: 2-8°C
• PKA: 7.90±0.40(Predicted)
• CAS DataBase Reference: 5-Benzyl-3,4-dihydro-3,3-dimethyl-2H-pyrrole(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Benzyl-3,4-dihydro-3,3-dimethyl-2H-pyrrole(116673-95-1)
• EPA Substance Registry System: 5-Benzyl-3,4-dihydro-3,3-dimethyl-2H-pyrrole(116673-95-1)

Safety Data

• Hazardous Substances Data: 116673-95-1(Hazardous Substances Data)

Usage

General Description

5-Benzyl-3,4-dihydro-3,3-dimethyl-2H-pyrrole, also known as vilazodone, is a chemical compound used in the treatment of depression. It is a selective serotonin reuptake inhibitor and partial serotonin receptor agonist, which means it works by increasing the levels of serotonin in the brain to improve mood and reduce symptoms of depression. Vilazodone is also used to treat anxiety disorders, and is commonly sold under the brand name Viibryd. It is typically taken orally in tablet form and has been found to be effective in improving symptoms of depression in clinical trials. However, like all medications, it may have potential side effects and should be used under the guidance of a healthcare professional.

InChI:InChI=1/C13H17N/c1-13(2)9-12(14-10-13)8-11-6-4-3-5-7-11/h3-7H,8-10H2,1-2H3

Synthetic route

2,2-dimethyl-5-phenylpent-4-yn-1-amine oxalate → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
With silver tetrafluoroborate In dichloromethane for 6h; Reflux;	100%

(E)-N-(2,2-dimethyl-5-phenylpent-4-yn-1-ylidene)benzylamine (1198092-67-9) + oxalic acid (144-62-7) → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
Stage #1: (E)-N-(2,2-dimethyl-5-phenylpent-4-yn-1-ylidene)benzylamine With potassium 3,7-dimethyloctan-3-olate In tetrahydrofuran at 0℃; for 1h; Stage #2: oxalic acid With water In toluene for 0.5h; Reflux; Stage #3: With silver tetrafluoroborate In dichloromethane at 40℃; for 6h;	100%

benzyl chloride (100-44-7) + 4-chloro-3,3-dimethylbutyronitrile (116673-94-0) → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
Stage #1: benzyl chloride With magnesium Stage #2: 4-chloro-3,3-dimethylbutyronitrile In diethyl ether; toluene for 5h; Reflux;	70%
With magnesium 1.) ether, reflux, 2 h, 2.) DMSO, 110-120 deg C, 3 h; Yield given. Multistep reaction;
Stage #1: benzyl chloride With magnesium In diethyl ether Grignard reaction; Stage #2: 4-chloro-3,3-dimethylbutyronitrile In diethyl ether; toluene for 5h; Grignard reaction; Reflux;

4-chloro-3,3-dimethylbutyronitrile (116673-94-0) + benzylmagnesium chloride (6921-34-2) → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
Stage #1: 4-chloro-3,3-dimethylbutyronitrile; benzylmagnesium chloride In diethyl ether for 2h; Reflux; Stage #2: In toluene for 3h; Reflux;	70%

(E)-2,2-dimethyl-5-phenyl-4-pentenyl-1-amine (399559-70-7) → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
With N-methylcyclohexylamine; Allyl acetate; potassium carbonate; [RuCl2(CO)3]2*1,3-bis(diphenylphosphino)propane at 120℃; for 22h;

3,3-dimethyl-4-hydroxy butyronitrile (103804-80-4) → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 71 percent / SOCl2, pyridine / 0.17 h / Heating 2: 1.) Mg / 1.) ether, reflux, 2 h, 2.) DMSO, 110-120 deg C, 3 h View Scheme
Multi-step reaction with 2 steps 1.1: pyridine; thionyl chloride / 0 °C 2.1: diethyl ether / 2 h / Reflux 2.2: 3 h / Reflux View Scheme

2,2-Dimethyl-3-chlor-propanol-1-ol → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 21 percent / dimethylsulfoxide / 6 h / 150 - 160 °C 2: 71 percent / SOCl2, pyridine / 0.17 h / Heating 3: 1.) Mg / 1.) ether, reflux, 2 h, 2.) DMSO, 110-120 deg C, 3 h View Scheme

C13H18ClN → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
With hydrogenchloride In water at 0 - 45℃; for 1.75 - 2h; pH=0.5 - 1.5; Industry scale;

2,2-dimethyl-4-oxo-5-phenyl-1-nitropentane (950672-88-5) → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
Stage #1: 2,2-dimethyl-4-oxo-5-phenyl-1-nitropentane With hydrogen; Raney nickel In methanol at 50 - 60℃; under 750.075 - 3000.3 Torr; Stage #2: With hydrogenchloride In water; toluene at 15 - 45℃; for 0.25 - 0.333333h; Stage #3: In water at 5 - 10℃; pH=10 - 11; Alkaline conditions;

5.5-dimethyl-1,3,2-dioxathiane-2-oxide (1003-85-6) → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dimethyl sulfoxide / 36 h / 100 °C 2.1: pyridine; thionyl chloride / 0 °C 3.1: diethyl ether / 2 h / Reflux 3.2: 3 h / Reflux View Scheme

2,2-Dimethyl-1,3-propanediol (126-30-7) → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: thionyl chloride / dichloromethane / 5 - 10 °C 2.1: dimethyl sulfoxide / 36 h / 100 °C 3.1: pyridine; thionyl chloride / 0 °C 4.1: diethyl ether / 2 h / Reflux 4.2: 3 h / Reflux View Scheme

C13H17N → 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1)

Conditions	Yield
With [(η5-C5Me4CH2CH2NZrNMe2)3] In benzene-d6 at 40℃; for 2h; Glovebox; Inert atmosphere;	> 95 %Spectr.

4-chlorobenzoylmethyl bromide (536-38-9) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-56-5)

Conditions	Yield
Stage #1: 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole With sodium hydrogencarbonate In methanol Stage #2: 4-chlorobenzoylmethyl bromide In methanol for 20h; Stage #3: With water at 40℃; for 1h;	84%
With sodium hydrogencarbonate In ethanol at 20℃; for 36h;	25%
With sodium hydrogencarbonate In ethanol; water at 20℃; for 36h;	25%

2-bromo-1-(5-chloro-thiophen-2-yl)-ethanone (57731-17-6) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 6-(5-chloro-thiophen-2-yl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (174347-68-3)

Conditions	Yield
In dichloromethane for 4h; Ambient temperature;	46%

α-bromoacetophenone (70-11-1) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 2,2-Dimethyl-6,7-diphenyl-2,3-dihydro-1H-pyrrolizin (116673-96-2)

Conditions	Yield
With sodium hydrogencarbonate In ethanol 1.) room temp., 24 h, 2.) 24 h;	42%
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

2-bromo-1-thiophen-3-yl-ethanone (1468-82-2) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 2,2-dimethyl-7-phenyl-6-(thiophen-3-yl)-2,3-dihydro-1H-pyrrolizine (174347-70-7)

Conditions	Yield
In dichloromethane for 4h; Ambient temperature;	34%

1-(benzofuran-2-yl)-2-bromoethan-1-one (23489-36-3) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 6-(benzo[b]furan-2-yl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (174347-72-9)

Conditions	Yield
In dichloromethane for 4h; Ambient temperature;	27.5%

1-(2-furyl)-2-bromoethanone (15109-94-1) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 2,2-dimethyl-6-(furan-2-yl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (174347-74-1)

Conditions	Yield
In dichloromethane for 4h; Ambient temperature;	19%

α-bromophenylacetaldehyde (16927-13-2) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 2,2-Dimethyl-5,7-diphenyl-2,3-dihydro-1H-pyrrolizin (116673-97-3)

Conditions	Yield
	15%

2-bromo-1-(4'-hydroxyphenyl)-1-ethanone (2491-38-5) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 4-(6,6-Dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-2-yl)-phenol (156897-31-3)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

2-bromo-1-(2,5-dichlorophenyl)ethanone (4571-25-9) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 6-(2,5-Dichloro-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (156897-24-4)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

2-bromo-1-(3-chloro-phenyl)-ethanone (41011-01-2) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 6-(3-Chloro-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (156897-21-1)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

4-(phenoxy)phenacyl bromide (28179-33-1) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 2,2-Dimethyl-6-(4-phenoxy-phenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-57-6)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

4-Nitrophenacyl bromide (99-81-0) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 2,2-Dimethyl-6-(4-nitro-phenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine (156897-27-7)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;
Stage #1: 4-Nitrophenacyl bromide; 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole In ethanol at 20℃; for 24h; Stage #2: With sodium hydrogencarbonate In ethanol; water at 20℃; for 24h;

2-bromo-1-(2,3,4-trichlorophenyl)ethanone (79779-66-1) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 2,2-Dimethyl-7-phenyl-6-(2,3,4-trichloro-phenyl)-2,3-dihydro-1H-pyrrolizine (156897-25-5)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

2,4-dichlorophenacyl bromide (2631-72-3) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 6-(2,4-Dichloro-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (156897-22-2)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

2-bromo-1-(4-(tert-butyl)phenyl)ethanone (30095-47-7) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 6-(4-tert-Butyl-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (156897-26-6)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;
Stage #1: 2-bromo-1-(4-(tert-butyl)phenyl)ethanone; 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole In ethanol at 20℃; for 24h; Stage #2: With sodium hydrogencarbonate In ethanol; water at 20℃; for 24h;

2-bromo-1-(3,4-dichlorophenyl)ethanone (2632-10-2) + 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 6-(3,4-Dichloro-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (156897-23-3)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) + 2-chlorophenacyl bromide (5000-66-8) → 6-(2-Chloro-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (156897-20-0)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) + 2-bromo-4'-fluoroacetophenone (403-29-2) → 6-(4-Fluoro-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (133111-60-1)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 6-(4-Methoxy-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (156897-29-9)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) + 4-aminophenacyl bromide (23442-14-0) → 4-(6,6-Dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-2-yl)-phenylamine (1026837-71-7)

Conditions	Yield
With sodium hydrogencarbonate In diethyl ether; ethanol; water for 36h; Ambient temperature;

5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → (2,2-Dimethyl-6,7-diphenyl-2,3-dihydro-1H-pyrrolizin-5-yl)essigsaeure

Conditions	Yield
Multi-step reaction with 3 steps 1: NaHCO3 / diethyl ether; ethanol; H2O / 36 h / Ambient temperature 2: Cu / toluene / 0.25 h / Heating 3: 44 percent / 10percent aq. NaOH / ethanol / 0.17 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 42 percent / 2.) NaHCO3 / ethanol / 1.) room temp., 24 h, 2.) 24 h 2: 39 percent / Cu / toluene / 0.25 h / Heating 3: 58 percent / 1.) 10percent KOH, 2.) 6percent H3PO4 / ethanol / 1.) reflux, 15 min View Scheme

5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → (2,2-Dimethyl-6,7-diphenyl-2,3-dihydro-1H-pyrrolizin-5-yl)-essigsaeureethylester (116674-01-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaHCO3 / diethyl ether; ethanol; H2O / 36 h / Ambient temperature 2: Cu / toluene / 0.25 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 42 percent / 2.) NaHCO3 / ethanol / 1.) room temp., 24 h, 2.) 24 h 2: 39 percent / Cu / toluene / 0.25 h / Heating View Scheme

5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → licofelone (156897-06-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaHCO3 / diethyl ether; ethanol; H2O / 36 h / Ambient temperature 2: Cu / toluene / 0.25 h / Heating 3: 75.5 percent / 10percent aq. NaOH / ethanol / 0.17 h / Heating View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydrogencarbonate / ethanol / 36 h / 20 °C 2.1: tetrahydrofuran / 10 - 15 °C 2.2: 0.33 h / 25 - 30 °C 3.1: hydrazine hydrate; potassium hydroxide / ethylene diglycol / 7 h / 85 - 145 °C View Scheme
Multi-step reaction with 4 steps 1: sodium hydrogencarbonate / ethanol; water / 36 h / 20 °C 2: tetrahydrofuran / 10 - 15 °C 3: water / tetrahydrofuran / 0.33 h / 25 - 30 °C 4: hydrazine hydrate; potassium hydroxide / diethylene glycol / 7 h / 85 - 145 °C View Scheme
Multi-step reaction with 3 steps 1.1: ethanol / 0.5 h 2.1: tetrahydrofuran / 18 - 25 °C / Inert atmosphere 2.2: 0.33 h / 25 - 30 °C 3.1: hydrazine hydrate; potassium hydroxide / diethylene glycol / 50 - 145 °C View Scheme

5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → 2-(6-(4-tert-butylphenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: NaHCO3 / diethyl ether; ethanol; H2O / 36 h / Ambient temperature 2: Cu / toluene / 0.25 h / Heating 3: 58.8 percent / 10percent aq. NaOH / ethanol / 0.17 h / Heating View Scheme

5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole (116673-95-1) → [2-(4-Amino-phenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl]-acetic acid (156897-13-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaHCO3 / diethyl ether; ethanol; H2O / 36 h / Ambient temperature 2: Cu / toluene / 0.25 h / Heating 3: 73.4 percent / 10percent aq. NaOH / ethanol / 0.17 h / Heating View Scheme

Upstream product

• 1198092-67-9 (E)-N-(2,2-dimethyl-5-phenylpent-4-yn-1-ylidene)benzylamine 
• 144-62-7 oxalic acid 
• 950672-88-5 2,2-dimethyl-4-oxo-5-phenyl-1-nitropentane 
• 103804-80-4 3,3-dimethyl-4-hydroxy butyronitrile 
• 399559-70-7 (E)-2,2-dimethyl-5-phenyl-4-pentenyl-1-amine 
• 100-44-7 benzyl chloride 
• 116673-94-0 4-chloro-3,3-dimethylbutyronitrile 
• 6921-34-2 benzylmagnesium chloride 
• 126-30-7 2,2-Dimethyl-1,3-propanediol 
• 1003-85-6 5.5-dimethyl-1,3,2-dioxathiane-2-oxide 

Downstream Products

• 156897-31-3 4-(6,6-Dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-2-yl)-phenol 
• 156897-22-2 6-(2,4-Dichloro-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine 
• 156897-26-6 6-(4-tert-Butyl-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine 
• 156897-29-9 6-(4-Methoxy-phenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine 
• 1026837-71-7 4-(6,6-Dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-2-yl)-phenylamine 
• 116674-02-3 (2,2-Dimethyl-5,7-diphenyl-2,3-dihydro-1H-pyrrolizin-6-yl)-essigsaeureethylester 
• 911060-89-4 5-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine 
• 133111-56-5 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine 
• 1281816-29-2 1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)ethanone 
• 1281816-31-6 1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)propan-1-one 
• 1281816-32-7 1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)hexan-1-one 
• 1281816-34-9 2-chloro-1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)ethanone 
• 1281816-35-0 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl formate 
• 1281816-36-1 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl acetate 

Relevant articles and documents

An efficient synthesis of 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3- dihydro-lh-pyrrolizine, a key intermediate in the licofelone synthesis

An efficient synthesis of 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3- dihydro-1H-pyrrolizine, a key intermediate for the synthesis of licofelone, an anti-inflammatory drug currently undergoing evaluation of the phase-III clinical studies, is described. The method is based on a novel synthesis of unstable 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole, which is then treated with 2-bromo-1-(4-chlorophenyl)ethan-1-one. 2,2-Dimethyl-5-phenylpent-4-ynal with benzylamines provides the corresponding Schiff bases. Migration of the C=N double bond in these N-(2,2-dimethyl-5-phenylpent-4-yn-1-ylidene)benzylamines into conjugation with the aromatic ring using various base/solvent systems was studied. Acid hydrolysis of the formed Schiff bases then provided 2,2-dimethyl-5-phenylpent-4-yn-1-amine and 2,2-dimethyl-5-phenylpenta-3,4-dien- 1-amine; their ratio was influenced mainly by the reaction conditions. Cyclization of these amines using Ag or Au catalysts then led to 5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole.

Selective Incorporation of Primary Amines into a Trizirconium Imido System and Catalyic Cyclization of Aminoalkynes

The trinuclear zirconium imido complex [{LZr(NMe2)}3] (2, L = C5Me4CH2CH2N) was synthesized by amine elimination between Zr(NMe2)4 and endo-olefinic isomers of (tetramethylcyclopentadienyl)ethanamine (LH3) (1). To study the fundamental reactivity of the trizirconium system, reactions of 2 with primary amines were examined. Selective incorporations of the primary amines were observed, depending on steric and electronic natures of the amine substrates. The amine-incorporated complexes [(LZrNHR)(LHZrNHR)(LHZr)(μ-NHR)(μ3-NR)] (3, R = Pr, Et), [(LZrNHR)2(LHZr)(μ-NR)] (4, R = Pr, i-Bu), [(LZr)2(LZrNMe2)(μ-NR)] (5, R = neo-Pen), and [(LZr)(LZrNHAr)(LH2Zr)(μ-NAr)2] (6, Ar = Ph, C6H4-4-Br, C6H4-4-OMe) were structurally characterized by NMR and XRD analysis and showed several coordination modes of the substrate nitrogen ligands: i.e., terminal amides, bridging amides, and bridging imides but not terminal imides. Thermolysis of a mixture of 3 and 4 led to C-H bond activation, giving rise to the zirconaaziridines [{LZr(η2-NCHR)}(LZr)(LHZr)(μ-NHCH2R)] (12, R = Et, Me). Complex 2 proved to be a competent precatalyst in the hydroamination of the aminoalkynes (H2NCH2CR12CH2C=CR2) (13, R1 = H, R2 = Bu, Ph, t-Bu; 14, R1 = Me, R2 = Et, Ph). Stoichiometric or semicatalytic reactions of 2 and the aminoalkynes were studied to explore the reactivity of in situ formed Zr3 species.

Licofelone-nitric oxide donors as anticancer agents

Five licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H- pyrrolizin-5-yl]acetic acid) nitric oxide donor conjugates were developed by a parallel synthesis approach. The biological screening revealed that compounds with a propyl (6b), butyl (6c), or octyl (6d) chain between licofelone and the nitric oxide donor exhibited high antiproliferative potency at MCF-7 and MDA-MB-231 breast cancer as well as at HT-29 colon cancer cells. Moreover, 6b-d possessed at least 2-fold higher cytotoxicity at MDA-MB-231 cells than the parent compound licofelone although they showed less inhibitory activity at COX-1 and COX-2. A correlation between COX inhibition and growth inhibitory properties is not visible. However, the high levels of nitric oxide production of the compounds may result in their high cytotoxic activity. Non-steroidal anti-inflammatory drugs possessing nitric oxide donors are promising anti-inflammatory and anticancer drugs. Herein, a series of licofelone-nitric oxide donors was synthesized and evaluated for their primary biological activities.