6052-73-9

Basic information

• Product Name: 5,6-dihydro-1H-pyridin-2-one
• Synonyms: 5,6-dihydro-1H-pyridin-2-one;5,6-Dihydro-2(1H)-pyridinone;1,5,6-trihydropyridin-2-one;2(1H)-Pyridinone, 5,6-dihydro-;3,4-Dehydro-2-piperidone;5,6-Dihydro-2(1H)-pyridone;5,6-Dihydropyridin-2(1H)-one;5-AMino-2-pentenoic Acid LactaM
• CAS NO: 6052-73-9
• Molecular Formula: C₅H₇NO
• Molecular Weight: 97.1152
• Product Categories: Amines;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 6052-73-9.mol
• Article Data: 22

Chemical Properties

• Melting Point: 187-188℃
• Boiling Point: 287 °C at 760 mmHg
• Flash Point: 158 °C
• Appearance: /
• Density: 1.052 g/cm³
• Vapor Pressure: 0.00256mmHg at 25°C
• Refractive Index: 1.478
• Storage Temp.: 2-8°C
• PKA: 15.07±0.20(Predicted)
• CAS DataBase Reference: 5,6-dihydro-1H-pyridin-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: 5,6-dihydro-1H-pyridin-2-one(6052-73-9)
• EPA Substance Registry System: 5,6-dihydro-1H-pyridin-2-one(6052-73-9)

Safety Data

• Hazardous Substances Data: 6052-73-9(Hazardous Substances Data)

Usage

Uses

A new pyridone alkaloid as an intermediate in the synthesis of Piperlongumine (P482850).

InChI:InChI=1/C5H7NO/c7-5-3-1-2-4-6-5/h1,3H,2,4H2,(H,6,7)

Synthetic route

6-oxo-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (128372-89-4) → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
With hydrogenchloride In methanol; water at 0℃; for 1h; Inert atmosphere;	98%
With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 2h;	72%
With trifluoroacetic acid In dichloromethane at 20℃; Inert atmosphere;

3-(phenylselanyl)-1-(trimethylsilyl)piperidin-2-one → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
With dihydrogen peroxide In tetrahydrofuran at 0 - 20℃; for 2h;	97.7%
In tetrahydrofuran at 0 - 20℃; for 2h;	0.55 g

(E)-N-(but-3-en-1-yl)but-2-enamide → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In dichloromethane for 2h; Reflux;	94%
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In dichloromethane at 40℃; for 2h;	56%

3-(phenylthio)piperidin-2-one (104261-03-2) → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
Stage #1: 3-(phenylthio)piperidin-2-one With sodium hydrogencarbonate In dichloromethane for 0.166667h; Stage #2: With 3-chloro-benzenecarboperoxoic acid for 1h; Further stages.;	90%
Stage #1: 3-(phenylthio)piperidin-2-one With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 2h; Stage #2: In toluene for 1h; Reflux;	80%
Multi-step reaction with 2 steps 1: m-CPBA, aq.NaHCO3 / CH2Cl2 / 1 h / 0 °C 2: 1.17 g / benzene / 1 h / Heating View Scheme

N-(but-3-en-1-yl)prop-2-enamide (1415686-28-0) → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In toluene at 85 - 90℃; for 7h;	75%
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In dichloromethane for 6h; Grubbs Olefin Metathesis; Reflux;	70%
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In dichloromethane for 6h; Reflux;	70%

2-oxopiperidin-3-yl dimethyldithiocarbamate → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
at 260℃; under 1 Torr;	68%

1-(perfluorobenzoyl)-5,6-dihydropyridin-2(1H)-one → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
With lithium hydroxide monohydrate In tetrahydrofuran at 50℃; for 4h;	68%

(E)-2,4-pentadienoic acid (21651-12-7) → 5,6-dihydro-2(1H)-pyridinone (6052-73-9) + 1,6-dihydropyridin-2(3H)-one (61892-77-1)

Conditions	Yield
With ammonia Yield given. Yields of byproduct given;

3-Benzenesulfonyl-piperidin-2-one → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
In benzene for 1h; Heating;	1.17 g

3-(Phenylselenenyl)-2-piperidinone → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
With dihydrogen peroxide In tetrahydrofuran 1.) 0 deg C, 30 min, 2.) 25 deg C, 1.5 h; Yield given;

1-(trimethylsilyl)piperidin-2-one (3553-93-3) → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: LDA / tetrahydrofuran; hexane / 1.) -50 deg C, 45 min, 2.) -78 deg C, 7 h 2: 50percent H2O2 / tetrahydrofuran / 1.) 0 deg C, 30 min, 2.) 25 deg C, 1.5 h View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 0.75 h / -50 °C / Inert atmosphere 1.2: 7 h / -78 °C / Inert atmosphere 2.1: dihydrogen peroxide / tetrahydrofuran / 2 h / 0 - 20 °C View Scheme

1-(methoxymethyl)-3-(phenylthio)piperidin-2-one (1026076-90-3) → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 78 percent / conc.HCl / ethanol / 6 h / Heating 2: m-CPBA, aq.NaHCO3 / CH2Cl2 / 1 h / 0 °C 3: 1.17 g / benzene / 1 h / Heating View Scheme
Multi-step reaction with 2 steps 1.1: hydrogenchloride / ethanol; water / 6 h / Reflux 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 2 h / 0 - 20 °C 2.2: 1 h / Reflux View Scheme

C2HF3O2*C11H8F5NO2 → 5,6-dihydro-2(1H)-pyridinone (6052-73-9) + (3E,9E,15E)-1,7,13-Triaza-cyclooctadeca-3,9,15-triene-2,8,14-trione

Conditions	Yield
With 4-methyl-morpholine In 1,4-dioxane at 80℃; for 18h;	A 6 mg B 36 mg

C8H13NO → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride Grubbs Olefin Metathesis;

2-oxopiperidine-1-carboxylic acid tert-butyl ester (85908-96-9) → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium; diisopropylamine / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 1.5 h / Inert atmosphere 2.1: 3-chloro-benzenecarboperoxoic acid; sodium hydrogencarbonate / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 2.2: 3 h / 80 °C / Inert atmosphere 3.1: hydrogenchloride / methanol; water / 1 h / 0 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 1.5 h / -78 °C / Inert atmosphere 2.1: 3-chloro-benzenecarboperoxoic acid; sodium hydrogencarbonate / dichloromethane / 2 h / 0 °C 3.1: toluene / 3 h / 80 °C 4.1: trifluoroacetic acid / dichloromethane / 2 h / 0 - 20 °C View Scheme

N-(tert-butyloxycarbonyl)-3-(phenylthio)piperidine-2-one (358732-56-6) → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 3-chloro-benzenecarboperoxoic acid; sodium hydrogencarbonate / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 1.2: 3 h / 80 °C / Inert atmosphere 2.1: hydrogenchloride / methanol; water / 1 h / 0 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: 3-chloro-benzenecarboperoxoic acid; sodium hydrogencarbonate / dichloromethane / 2 h / 0 °C 2: toluene / 3 h / 80 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 0 - 20 °C View Scheme

piperidin-2-one (675-20-7) → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 16 h / 20 °C / Inert atmosphere 2.1: n-butyllithium; diisopropylamine / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 1.5 h / Inert atmosphere 3.1: 3-chloro-benzenecarboperoxoic acid; sodium hydrogencarbonate / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 3.2: 3 h / 80 °C / Inert atmosphere 4.1: hydrogenchloride / methanol; water / 1 h / 0 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 13 h / 0 - 20 °C 2: 2,5-di-tert-butyl-p-benzoquinone; palladium(II) trifluoroacetate; racemic methyl phenyl sulfoxide; zinc(II) trifluoroacetate; di-n-butylboryl trifluoromethanesulfonate; N-ethyl-N,N-diisopropylamine / dichloromethane; 1,4-dioxane / 24 h / 20 °C / Inert atmosphere; Sealed tube 3: lithium hydroxide monohydrate / tetrahydrofuran / 4 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine / toluene / 4 h / Inert atmosphere 2.1: tetrahydrofuran / 0.75 h / -50 °C / Alkaline conditions; Enzymatic reaction 2.2: 7 h 3.1: tetrahydrofuran / 2 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine / toluene / 4 h / 50 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran / 0.75 h / -50 °C / Inert atmosphere 2.2: 7 h / -78 °C / Inert atmosphere 3.1: dihydrogen peroxide / tetrahydrofuran / 2 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / dichloromethane; tetrahydrofuran / 0.5 h / 0 °C 1.2: 3 h 2.1: lithium diisopropyl amide / tetrahydrofuran / 0.75 h / -78 °C / Inert atmosphere 2.2: -78 - 20 °C 3.1: hydrogenchloride / ethanol; water / 6 h / Reflux 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 2 h / 0 - 20 °C 4.2: 1 h / Reflux View Scheme

1-(perfluorobenzoyl)piperidin-2-one → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 2,5-di-tert-butyl-p-benzoquinone; palladium(II) trifluoroacetate; racemic methyl phenyl sulfoxide; zinc(II) trifluoroacetate; di-n-butylboryl trifluoromethanesulfonate; N-ethyl-N,N-diisopropylamine / dichloromethane; 1,4-dioxane / 24 h / 20 °C / Inert atmosphere; Sealed tube 2: lithium hydroxide monohydrate / tetrahydrofuran / 4 h / 50 °C View Scheme

1-(methoxymethyl)piperidin-2-one (50902-27-7) → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 0.75 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C 2.1: hydrogenchloride / ethanol; water / 6 h / Reflux 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 2 h / 0 - 20 °C 3.2: 1 h / Reflux View Scheme

3-benzenesulfinyl-2-oxo-piperidine-1-carboxylic acid tert-butyl ester → 5,6-dihydro-2(1H)-pyridinone (6052-73-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 3 h / 80 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 0 - 20 °C View Scheme

5,6-dihydro-2(1H)-pyridinone (6052-73-9) → cis-3,4-dihydroxy-2-piperidinone (139374-43-9)

Conditions	Yield
osmium(VIII) oxide; 4-methylmorpholine N-oxide In tert-butyl alcohol Ambient temperature;	100%
With osmium(VIII) oxide; 4-methylmorpholine N-oxide In tert-butyl alcohol for 27h; Ambient temperature;	64 mg

[2-(hydroxymethyl)phenyl]dimethyl(4-fluorophenyl)silane (853955-70-1) + 5,6-dihydro-2(1H)-pyridinone (6052-73-9) → (R)-4-(4-fluorophenyl)-2-piperidinone

Conditions	Yield
With potassium hydroxide; (1R,4R)-2,5-diphenylbicyclo[2.2.2]octa-2,5-diene; bis(ethylene)rhodium(I) chloride dimer In tetrahydrofuran at 50℃; for 12h;	92%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + tris(4-chlorophenyl)boroxine (7519-91-7) → (R)-4-(4-chlorophenyl)-2-piperidinone

Conditions	Yield
With (R)-2,2'-bis(diarylphosphino)-1,1'-binaphthyl; water; bis(ethylene)rhodium acetylacetonate In 1,4-dioxane at 60℃; for 12h;	88%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + tris(4-fluorophenyl)boroxine (448-59-9) → (R)-4-(4-fluorophenyl)-2-piperidinone

Conditions	Yield
With (R)-2,2'-bis(diphenylphosphino)-octahydro-1,1'-binaphthyl; water; bis(ethylene)rhodium acetylacetonate In 1,4-dioxane at 40℃; for 12h;	84%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + C13H11ClN2O → (E)-1-(3-(4-((1H-imidazol-1-yl)methyl)phenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one

Conditions	Yield
Stage #1: 5,6-dihydro-2(1H)-pyridinone With sodium hydride In tetrahydrofuran; mineral oil at -5 - 0℃; for 2h; Stage #2: C13H11ClN2O In tetrahydrofuran; mineral oil for 21h;	82%
With triethylamine In tetrahydrofuran at 0℃; for 3h;

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + formic acid ethyl ester (109-94-4) → N-formyl-5,6-dihydropyridine-2(1H)-one

Conditions	Yield
With titanium tetrachloride; triethylamine In dichloromethane at 0℃; for 1h;	76%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + C23H24Cl2O7 → piperarborenine B

Conditions	Yield
In toluene at 20 - 80℃; for 12h; Inert atmosphere; Molecular sieve;	75%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + C16H9ClO5 → C21H15NO6

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 10h;	75%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) → 1-chloro-5,6-dihydropyridin-2(1H)-one (1215765-27-7)

Conditions	Yield
With N-chloro-succinimide; potassium tert-butylate In tetrahydrofuran at 20℃; for 0.666667h; Inert atmosphere;	74%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + p-phenylenediacrylic diacid dichloride (35288-49-4) → C22H20N2O4

Conditions	Yield
Stage #1: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #2: p-phenylenediacrylic diacid dichloride In tetrahydrofuran; hexane at -78℃; for 3h;	72%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + 2-Nitrobenzenesulfonyl chloride (1694-92-4) → 1-nosyl-5,6-dihydropyridin-2(1H)-one (1266568-91-5)

Conditions	Yield
Stage #1: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2-Nitrobenzenesulfonyl chloride In tetrahydrofuran; hexane at -78℃; for 1.5h; Inert atmosphere;	71%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + 2,2-diethoxy-ethanamine (645-36-3) → 5,6-Dihydroimidazo<1,2-a>pyridine

Conditions	Yield
titanium tetrachloride In 1,3,5-trimethyl-benzene for 74h; Heating;	68.9%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + C19H31NO5 → tert-butyl (E)-4-(2-methyl-3-oxo-3-(6-oxo-3,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)piperidine-1-carboxylate

Conditions	Yield
Stage #1: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: C19H31NO5 In tetrahydrofuran at -78 - 20℃; for 1h;	67.8%
Stage #1: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: C19H31NO5 In tetrahydrofuran at 20℃; for 1h;	67.8%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + chloroacetyl chloride (79-04-9) → 1-(2-chloroacetyl)-5,6-dihydropyridin-2(1H)-one

Conditions	Yield
Stage #1: 5,6-dihydro-2(1H)-pyridinone With sodium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: chloroacetyl chloride In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	65%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + C13H14Cl3NO → C18H20Cl2N2O2

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 10h;	65%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + cinnamyl chloride (2687-12-9) → 1-cinnamoyl-5,6-dihydropyridin-2(1H)-one (1057962-70-5)

Conditions	Yield
Stage #1: 5,6-dihydro-2(1H)-pyridinone With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Inert atmosphere; Stage #2: cinnamyl chloride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere;	64%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + mesitylenecarbonitrile oxide (2904-57-6) → 3-(2,4,6-trimethyl-phenyl)-5,6,7,7a-tetrahydro-3aH-isoxazolo[4,5-c]pyridin-4-one

Conditions	Yield
In benzene at 20℃; for 504000h; Cycloaddition;	62%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + C10H11ClN2O → (E)-1-{3-[(3,5,6-trimethylpyrazin-2-yl)]prop-2-enoyl}-5,6-dihydropyridin-2(1H)-one

Conditions	Yield
Stage #1: C10H11ClN2O With pivaloyl chloride; triethylamine In tetrahydrofuran at -20℃; for 0.75h; Stage #2: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran at -70℃; for 1.75h;	53%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + (2E)-3-(3,5,6-trimethylpyrazin-2-yl)prop-2-enoic acid → (E)-1-{3-[(3,5,6-trimethylpyrazin-2-yl)]prop-2-enoyl}-5,6-dihydropyridin-2(1H)-one

Conditions	Yield
Stage #1: (2E)-3-(3,5,6-trimethylpyrazin-2-yl)prop-2-enoic acid With pivaloyl chloride; triethylamine In tetrahydrofuran; dichloromethane at -20℃; Stage #2: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran for 1h;	53%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + (E)-(E)-3-(5-methoxypyrimidin-2-yl)acrylic pivalic anhydride → (E)-1-(3-(5-methoxypyrimidin-2-yl)acryloyl)-5,6-dihydropyridin-2(1H)-one

Conditions	Yield
Stage #1: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: (E)-(E)-3-(5-methoxypyrimidin-2-yl)acrylic pivalic anhydride In tetrahydrofuran; hexane at -78℃; for 1h;	52.23%
Stage #1: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: (E)-(E)-3-(5-methoxypyrimidin-2-yl)acrylic pivalic anhydride In tetrahydrofuran; hexane at -78℃; for 1h;	52.23%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + benzohydroximoyl chloride (698-16-8) → 3-phenyl-5,6,7,7a-tetrahydro-3aH-isoxazolo[4,5-c]pyridin-4-one

Conditions	Yield
With triethylamine In benzene at 20℃; for 48h; Cycloaddition; dehydrochlorination;	51%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + C19H31NO5 → (Z)-tert-butyl 4-(2-methyl-3-oxo-3-(2-oxo-5,6-dihydropyridin-1(2H)-yl)prop-1-enyl)piperidine-1-carboxylate

Conditions	Yield
Stage #1: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: C19H31NO5 In tetrahydrofuran at -78 - 20℃; for 1h;	49.6%
Stage #1: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: C19H31NO5 In tetrahydrofuran at 20℃; for 1h;	49.6%

5,6-dihydro-2(1H)-pyridinone (6052-73-9) + (E)-(E)-3-(3,5-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)acrylic pivalic anhydride → (E)-1-(3-(3,5-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)acryloyl)-5,6-dihydropyridin-2(1H)-one

Conditions	Yield
Stage #1: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: (E)-(E)-3-(3,5-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)acrylic pivalic anhydride In tetrahydrofuran; hexane at -78℃; for 1.5h;	48.92%
Stage #1: 5,6-dihydro-2(1H)-pyridinone With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: (E)-(E)-3-(3,5-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)acrylic pivalic anhydride In tetrahydrofuran at -78℃; for 1.5h;	48.92%

Upstream product

• 21651-12-7 (E)-2,4-pentadienoic acid 
• 128372-89-4 6-oxo-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 1415686-28-0 N-(but-3-en-1-yl)prop-2-enamide 
• 85908-96-9 2-oxopiperidine-1-carboxylic acid tert-butyl ester 
• 358732-56-6 N-(tert-butyloxycarbonyl)-3-(phenylthio)piperidine-2-one 
• 675-20-7 piperidin-2-one 
• 1026076-90-3 1-(methoxymethyl)-3-(phenylthio)piperidin-2-one 
• 104261-03-2 3-(phenylthio)piperidin-2-one 
• 3553-93-3 1-(trimethylsilyl)piperidin-2-one 
• 50902-27-7 1-(methoxymethyl)piperidin-2-one 

Downstream Products

• 20069-09-4 piperlongumine 
• 132143-27-2 1-(4-Nitrobenzoyl)-5,6-dihydropyridin-2(1H)-one (2d) 
• 1057962-70-5 1-cinnamoyl-5,6-dihydropyridin-2(1H)-one 
• 1415686-29-1 (E)-1-(3-(2,5-dimethoxylphenyl)prop-2-enoyl)-5,6-dihydropyridin-2(1H)-one 
• 1415686-30-4 (E)-1-(3-(4-bromophenyl)prop-2-enoyl)-5,6-dihydropyridin-2(1H)-one 
• 1415686-32-6 (E)-1-(3-(4-chlorophenyl)prop-2-enoyl)-5,6-dihydropyridin-2(1H)-one 
• 1415686-34-8 (E)-1-(3-mesitylacryloyl)-5,6-dihydropyridin-2(1H)-one 
• 1415686-35-9 C₂₀H₁₇NO₃ 
• 1415686-39-3 C₁₂H₁₀FNO₂ 
• 1415686-40-6 C₁₂H₁₀ClNO₂ 
• 1415686-41-7 C₁₂H₁₀INO₂ 
• 1415686-42-8 C₂₃H₁₉N₃O₂ 
• 1415686-43-9 C₁₈H₁₇N₃O₂ 
• 1415686-45-1 C₂₁H₂₃NO₅ 

Relevant articles and documents

Design, synthesis, and biological evaluation of a novel indoleamine 2,3-dioxigenase 1 (IDO1) and thioredoxin reductase (TrxR) dual inhibitor

Targeting the Trp-Kyn pathway is an attractive approach for cancer immunotherapy. Thioredoxin reductase (TrxR) enzymes are reactive oxygen species (ROS) modulators that are involved in the tumor cell growth and survival processes. The 4-phenylimidazole scaffold is well-established as useful for indoleamine 2,3-dioxygenase 1 (IDO1) inhibition, while piperlongumine (PL) and its derivatives have been reported to be inhibitors of TrxR. To take advantage of both immunotherapy and TrxR inhibition, we designed a first-generation dual IDO1 and TrxR inhibitor (ZC0101) using the structural combination of 4-phenylimidazole and PL scaffolds. ZC0101 exhibited better dual inhibition against IDO1 and TrxR in vitro and in cell enzyme assays than the uncombined forms of 4-phenylimidazole and PL. It also showed antiproliferative activity in various cancer cell lines, and a selective killing effect between normal and cancer cells. Furthermore, ZC0101 effectively induced apoptosis and ROS accumulation in cancer cells. Knockdown of TrxR1 and IDO1 expression induced cellular enzyme inhibition and ROS accumulation effects during ZC0101 treatment, but only reduced TrxR1 expression was able to improve ZC0101′s antiproliferation effect. This proof-of-concept study provides a novel strategy for cancer treatment. ZC0101 represents a promising lead compound for the development of novel antitumor agents that can also be used as a valuable probe to clarify the relationships and mechanisms of cancer immunotherapy and ROS modulators.

Activity-based protein profiling reveals GSTO1 as the covalent target of piperlongumine and a promising target for combination therapy for cancer

Through systematic target identification for piperlongumine, a cancer-selective killing molecule, we identified GSTO1 as its major covalent target for cancer cell death induction. We also reveal that GSTO1 inhibition is a promising combination strategy with other anti-cancer agents by drug combination screening in which piperlongumine exhibits broad-spectrum synergistic effects with a large proportion of the tested anti-cancer agents, especially with PI3K/Akt/mTOR pathway inhibitors.