41419-12-9

Basic information

• Product Name: 3,3-dichloropiperidin-2-one
• CAS NO: 41419-12-9
• Molecular Formula: C₅H₇Cl₂NO
• Molecular Weight: 168.0212
• Mol File: 41419-12-9.mol
• Article Data: 27

Chemical Properties

• Boiling Point: 316.7°C at 760 mmHg
• Flash Point: 145.3°C
• Density: 1.38g/cm³
• Vapor Pressure: 0.000403mmHg at 25°C
• Refractive Index: 1.515
• CAS DataBase Reference: 3,3-dichloropiperidin-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: 3,3-dichloropiperidin-2-one(41419-12-9)
• EPA Substance Registry System: 3,3-dichloropiperidin-2-one(41419-12-9)

Safety Data

• Hazardous Substances Data: 41419-12-9(Hazardous Substances Data)

Usage

General Description

3,3-dichloropiperidin-2-one is a chemical compound with the molecular formula C5H8Cl2NO. It belongs to the class of organic compounds known as piperidinones, which are compounds containing a piperidine ring, a six-membered saturated aliphatic heterocycle, with one ketone group. The piperidinone ring in this compound is dichlorinated, meaning it has two chlorine atoms attached. 3,3-dichloropiperidin-2-one exhibits specialty in various fields such as in the pharma industry for drug synthesis, particularly for its antifungal and other activity. 3,3-dichloropiperidin-2-one should be handled with adequate safety measures given its potential risk in causing skin and eye irritation, and toxicity to specific target organs after prolonged or repeated exposure.

Synthetic route

piperidin-2-one (675-20-7) → 3,3-dichloro-piperidin-2-one (41419-12-9)

Conditions	Yield
With phosphorus pentachloride In chloroform Reflux;	85%
With phosphorus pentachloride In chloroform at 0℃; for 3h; Heating / reflux;	85%
With phosphorus pentachloride In chloroform at 0 - 70℃; for 4h;	77%

chloroform (67-66-3) + Cyclopentanone oxime (1192-28-5) → 3,3-dichloro-piperidin-2-one (41419-12-9)

Conditions	Yield
With phosphorus pentachloride; trichlorophosphate at 0 - 70℃; for 4h;	81%

5,5,6-trichloro-2,3,4,5-tetrahydro-pyridine (876490-05-0) → 3,3-dichloro-piperidin-2-one (41419-12-9)

Conditions	Yield
With water

Cyclopentanone oxime (1192-28-5) → 3,3-dichloro-piperidin-2-one (41419-12-9)

Conditions	Yield
With phosphorus pentachloride; xylene Behandeln des Reaktionsgemisches mit Eis;

5,5,6-trichloro-2,3,4,5-tetrahydro-pyridine (876490-05-0) + water (7732-18-5) → 3,3-dichloro-piperidin-2-one (41419-12-9)

3-chloro-piperidin-2-one (16834-22-3) → 3,3-dichloro-piperidin-2-one (41419-12-9)

Conditions	Yield
With phosphorus pentachloride In chloroform at 20℃;

3,3-dichloro-piperidin-2-one (41419-12-9) → 3,3-dihydroxypiperidin-2-one

Conditions	Yield
With sodium carbonate In water at 20℃; for 2h;	96%

morpholine (110-91-8) + 3,3-dichloro-piperidin-2-one (41419-12-9) → 3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (545445-40-7)

Conditions	Yield
With triethylamine In 1,4-dioxane at 110℃; for 4.5h;	92%
for 2h; Reflux;	74%
at 140℃; for 12h;	55%

3,3-dichloro-piperidin-2-one (41419-12-9) → 3-chloro-5,6-dihydro-1H-pyridin-2-one (207976-92-9)

Conditions	Yield
With lithium carbonate; lithium chloride In N,N-dimethyl-formamide at 130℃; for 4h;	90%
With lithium carbonate In N,N-dimethyl-formamide at 120℃; for 24h;	87%
With lithium carbonate; lithium chloride In N,N-dimethyl-formamide Inert atmosphere; Heating;	65.6%

3,3-dichloro-piperidin-2-one (41419-12-9) → 3-chloro-5,6-dihydro-2(1H)-pyridinone (1314925-89-7)

Conditions	Yield
With lithium carbonate In DMF (N,N-dimethyl-formamide) at 120℃; for 24h; Heating / reflux;	87%

3,3-dichloro-piperidin-2-one (41419-12-9) → Δ1-pyrroline-5-carboxylate (2906-39-0)

Conditions	Yield
With barium dihydroxide

3,3-dichloro-piperidin-2-one (41419-12-9) → rac-Pro-OH (609-36-9)

Conditions	Yield
With barium dihydroxide anschliessend Erhitzen mit wss. H2SO4 und Hydrieren des Reaktionsprodukts an Platin in H2O;

3,3-dichloro-piperidin-2-one (41419-12-9) + water (7732-18-5) + barium hydroxide → Δ1-pyrroline-5-carboxylate (2906-39-0)

3,3-dichloro-piperidin-2-one (41419-12-9) → 3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (545445-40-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium carbonate / N,N-dimethyl-formamide / 7 h / 120 °C 2: lithium carbonate / N,N-dimethyl-formamide / 3 h / 130 °C View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → (E)-3-morpholino-1-(3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one (1571062-01-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium carbonate / N,N-dimethyl-formamide / 7 h / 120 °C 2: lithium carbonate / N,N-dimethyl-formamide / 3 h / 130 °C 3: tetrahydrofuran / 12 h / 20 °C / Inert atmosphere View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → (E)-1-(2-methyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-3-morpholino-5,6-dihydropyridine-2(1H)-one (1571062-06-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium carbonate / N,N-dimethyl-formamide / 7 h / 120 °C 2: lithium carbonate / N,N-dimethyl-formamide / 3 h / 130 °C 3: tetrahydrofuran / 12 h / 20 °C / Inert atmosphere View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → (E)-3-morpholino-1-(2-(3,4,5-trimethoxybenzylidene)butanoyl)-5,6-dihydropyridine-2(1H)-one (1571062-07-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium carbonate / N,N-dimethyl-formamide / 7 h / 120 °C 2: lithium carbonate / N,N-dimethyl-formamide / 3 h / 130 °C 3: tetrahydrofuran / 12 h / 20 °C / Inert atmosphere View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → (E)-3-morpholino-1-(2-(3,4,5-trimethoxybenzylidene)pentanoyl)-5,6-dihydropyridine-2(1H)-one (1571062-08-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium carbonate / N,N-dimethyl-formamide / 7 h / 120 °C 2: lithium carbonate / N,N-dimethyl-formamide / 3 h / 130 °C 3: tetrahydrofuran / 12 h / 20 °C / Inert atmosphere View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → (Ε)-3-chloro-1-(3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1Η)-one (1571062-00-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium carbonate / N,N-dimethyl-formamide / 7 h / 120 °C 2: tetrahydrofuran / 12 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: lithium carbonate; lithium chloride / N,N-dimethyl-formamide / 120 °C 2.1: n-butyllithium / tetrahydrofuran / 0.25 h / -78 °C / Schlenk technique; Inert atmosphere 2.2: -78 - 23 °C / Schlenk technique; Inert atmosphere View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → (E)-3-chloro-1-(2-methyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridine-2(1H)-one (1571062-03-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium carbonate / N,N-dimethyl-formamide / 7 h / 120 °C 2: tetrahydrofuran / 12 h / 20 °C / Inert atmosphere View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → (E)-3-chloro-1-(2-ethyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one (1571062-04-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium carbonate / N,N-dimethyl-formamide / 7 h / 120 °C 2: tetrahydrofuran / 12 h / 20 °C / Inert atmosphere View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → (E)-3-chloro-1-(2-propyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one (1571062-05-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium carbonate / N,N-dimethyl-formamide / 7 h / 120 °C 2: tetrahydrofuran / 12 h / 20 °C / Inert atmosphere View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → (E)-3-chloro-1-(2-butyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one (1571062-19-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium carbonate / N,N-dimethyl-formamide / 7 h / 120 °C 2: tetrahydrofuran / 12 h / 20 °C / Inert atmosphere View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → 1-(4-methoxyphenyl)-6-(4-(N-methyl-N-isobutyrylamino)phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium carbonate / N,N-dimethyl-formamide / 12 h / 20 - 120 °C 2: triethylamine / toluene / 12 h / Reflux 3: potassium carbonate; 1,10-Phenanthroline / dimethyl sulfoxide / 12 h / 20 - 120 °C / Inert atmosphere View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → 1-(4-methoxyphenyl)-6-(4-(N-methyl-N-isobutyrylamino)phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide

Conditions	Yield
Multi-step reaction with 4 steps 1: lithium carbonate / N,N-dimethyl-formamide / 12 h / 20 - 120 °C 2: triethylamine / toluene / 12 h / Reflux 3: potassium carbonate; 1,10-Phenanthroline / dimethyl sulfoxide / 12 h / 20 - 120 °C / Inert atmosphere 4: ammonia / ethylene glycol / 3.5 h / 120 °C / Sealed tube View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → 1-(4-methoxyphenyl)-6-(4-(6-bromohexanoylamino)phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium carbonate / N,N-dimethyl-formamide / 12 h / 20 - 120 °C 2: triethylamine / toluene / 12 h / Reflux 3: dmap / dichloromethane / 4 h / 20 °C View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → 1-(4-methoxyphenyl)-6-(4-(2-oxoazepan-1-yl)phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 4 steps 1: lithium carbonate / N,N-dimethyl-formamide / 12 h / 20 - 120 °C 2: triethylamine / toluene / 12 h / Reflux 3: dmap / dichloromethane / 4 h / 20 °C 4: potassium tert-butylate / tetrahydrofuran / 3 h / 0 - 20 °C View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → 1-(4-methoxyphenyl)-6-(4-(2-oxoazepan-1-yl)phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide

Conditions	Yield
Multi-step reaction with 5 steps 1: lithium carbonate / N,N-dimethyl-formamide / 12 h / 20 - 120 °C 2: triethylamine / toluene / 12 h / Reflux 3: dmap / dichloromethane / 4 h / 20 °C 4: potassium tert-butylate / tetrahydrofuran / 3 h / 0 - 20 °C 5: ammonia / ethylene glycol / 3.5 h / 120 °C / Sealed tube View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → 1-(4-methoxyphenyl)-6-(4-(5-methyl-2-oxopyridin-1(2H)-yl)phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-3-formamide

Conditions	Yield
Multi-step reaction with 4 steps 1: lithium carbonate / N,N-dimethyl-formamide / 12 h / 20 - 120 °C 2: triethylamine / toluene / 12 h / Reflux 3: potassium carbonate; 1,10-Phenanthroline; copper(l) iodide / dimethyl sulfoxide / 12 h / 120 °C / Inert atmosphere 4: ammonia / ethylene glycol / 3.5 h / 120 °C / Sealed tube View Scheme

3,3-dichloro-piperidin-2-one (41419-12-9) → C28H26N4O5

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium carbonate / N,N-dimethyl-formamide / 12 h / 20 - 120 °C 2: triethylamine / toluene / 12 h / Reflux 3: potassium carbonate; 1,10-Phenanthroline; copper(l) iodide / dimethyl sulfoxide / 12 h / 120 °C / Inert atmosphere View Scheme

Upstream product

• 675-20-7 piperidin-2-one 
• 876490-05-0 5,5,6-trichloro-2,3,4,5-tetrahydro-pyridine 
• 1192-28-5 Cyclopentanone oxime 
• 7732-18-5 water 
• 16834-22-3 3-chloro-piperidin-2-one 
• 67-66-3 chloroform 

Downstream Products

• 2906-39-0 Δ¹-pyrroline-5-carboxylate 
• 609-36-9 rac-Pro-OH 
• 545445-40-7 3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one 
• 207976-92-9 3-chloro-5,6-dihydro-1H-pyridin-2-one 
• 1571062-01-5 (E)-3-morpholino-1-(3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one 
• 1571062-06-0 (E)-1-(2-methyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-3-morpholino-5,6-dihydropyridine-2(1H)-one 
• 1571062-07-1 (E)-morpholino-1-(2-ethyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one 
• 1571062-08-2 (E)-morpholino-1-(2-propyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one 
• 1571062-00-4 (Ε)-3-chloro-1-(3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1Η)-one 
• 1571062-03-7 (E)-3-chloro-1-(2-methyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridine-2(1H)-one 
• 1571062-04-8 (E)-3-chloro-1-(2-ethyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one 
• 1571062-05-9 (E)-3-chloro-1-(2-propyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one 
• 1571062-19-5 (E)-3-chloro-1-(2-butyl-3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one 

Relevant articles and documents

Radiosensitization of human pancreatic cancer by piperlongumine analogues

Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by 2 months in combination with gemcitabine. However, prognosis and survival improvement remain unsatisfactory, and effective therapies are urgently needed. Piperlongumine has been demonstrated to have therapeutic potentials against various cancers. In this study, we synthesized a series of piperlongumine derivatives and provided evidence that piperlongumine derivatives could be used as effective radiosensitizers in pancreatic cancer. Two compounds enhanced the radiosensitivity of Panc-1 and SW1990 cells. In a pancreatic bi-flank xenograft tumor model, they significantly inhibited tumor growth. Piperlongumine derivatives could induce reactive oxygen species (ROS) expression and regulate the Keap1-Nrf2 protective pathway with enhancement of radiation-induced DNA damage, G2/M-phase cell cycle arrest, and apoptosis. Collectively, our data offer a proof of concept for the use of piperlongumine derivatives as a novel class of radiosensitizers for the treatment of pancreatic cancer.

DERIVATIVES OF PIPERLONGUMINE AND USES THEREOF

The present invention relates to a group of 1-[(E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoyl]-2,3-dihydropyridin-6-one (piperlongumine) derivatives, analogs and pharmaceutically acceptable salts thereof. The present invention also relates to a pharmaceutical composition and formulation containing a derivative of piperlongumine; and use of the derivatives and analogs for treating cancer, reducing inflammation and/or treating an autoimmune or inflammatory disease.

Novel Ligustrazine-Based Analogs of Piperlongumine Potently Suppress Proliferation and Metastasis of Colorectal Cancer Cells in Vitro and in Vivo

Piperlongumine 1 increases reactive oxygen species (ROS) levels and preferably induces cancer cell apoptosis by triggering different pathways. However, the poor solubility of 1 limits its intensive investigation and clinical application. Ligustrazine possesses a water-soluble pyrazine skeleton and can inhibit proliferation and metastasis of cancer cells. We synthesized compound 3 by replacement of the trimethoxyphenyl of 1 with ligustrazine moiety and further introduced 2-Cl, -Br, and -I to 3 for synthesis of 4-6, respectively. Compound 4 possessed 14-fold greater aqueous solubility than 1 and increased ROS levels in colorectal cancer HCT-116 cells. Additionally, 4 preferably inhibited proliferation, migration, invasion, and heteroadhesion of HCT-116 cells. Treatment with 4 suppressed tumor growth and lung metastasis in vivo and prolonged the survival of tumor-bearing mice. Furthermore, 4 mitigated TGF-β1-induced epithelial-mesenchymal transition and Wnt/β-catenin activation by inhibiting the Akt and GSK-3β phosphorylation in HCT-116 cells. Collectively, 4 displayed significant antiproliferation and antimetastasis activities, superior to 1.