158681-13-1

Basic information

• Product Name: Rimonabant hydrochloride
• Synonyms: RIMONABANT HYDROCHLORIDE;5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-n-1-piperidinyl-1h-pyrazole-3-carboxamide monohydrochloride;ACOMPLIA;ACOMPLIA (RIMONABANT;RIMONABANT HCL;Rimonabant(Acomplia);RimonabantConsultedStandard;Acomplia, SR141716
• CAS NO: 158681-13-1
• Molecular Formula: C₂₂H₂₁Cl₃N₄O*ClH
• Molecular Weight: 500.25
• EINECS: 233-720-0
• Product Categories: API;Cnbio;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Aromatics;Heterocycles;SR141716
• Mol File: 158681-13-1.mol
• Article Data: 12

Chemical Properties

• Melting Point: 230-240°C
• Boiling Point: 627.6 °C at 760 mmHg
• Flash Point: 333.3 °C
• Appearance: white to beige/
• Storage Temp.: -20°C Freezer
• Solubility: DMSO: soluble20mg/mL, clear
• CAS DataBase Reference: Rimonabant hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Rimonabant hydrochloride(158681-13-1)
• EPA Substance Registry System: Rimonabant hydrochloride(158681-13-1)

Safety Data

• Hazard Codes: T,Xi
• Statements: 25-36
• Safety Statements: 26-45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 158681-13-1(Hazardous Substances Data)

Usage

Chemical Properties

White to Off-White Crystalline Solid

Uses

Different sources of media describe the Uses of 158681-13-1 differently. You can refer to the following data:
1. The first of a new class of selective (Cannabinoid-1 (CB-1) receptor antagonists
2. A brain cannabinoid receptor (CB1) antagonist. Antiobesity agent.
3. Rimonabant hydrochloride has been used as an antagonist of cannabinoid 1 (CB1) receptor:to study its effects on protein synthesis in C2C12 myotubesto analyze its effects on human astrogliain combination with methanandamide (mAEA) to study its effects on murine gastric vagal afferent mechanosensitivity

Hazard

A poison.

Biochem/physiol Actions

Rimonabant acts as a mycobacterial membrane protein large 3 (MMPL3) inhibitor. Rimonabant hydrochloride exhibits therapeutic activity against weight reduction and smoking cessation.

InChI:InChI=1/C22H21Cl3N4O.ClH/c1-14-20(22(30)27-28-11-3-2-4-12-28)26-29(19-10-9-17(24)13-18(19)25)21(14)15-5-7-16(23)8-6-15;/h5-10,13H,2-4,11-12H2,1H3,(H,27,30);1H

Synthetic route

N-aminopiperidine hydrochloride (63234-70-8) + rimonabant acid (162758-35-2) + rimonabant (168273-06-1) → rimonabant hydrochloride (158681-13-1)

Conditions	Yield
Stage #1: rimonabant acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 6h; Stage #2: N-aminopiperidine hydrochloride With triethylamine In tetrahydrofuran at 60℃; for 1.5h; Stage #3: rimonabant With hydrogenchloride	92.7%

1-Aminopiperidine (2213-43-6) + 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbonyl chloride (168273-05-0) → rimonabant hydrochloride (158681-13-1)

Conditions	Yield
Stage #1: 1-Aminopiperidine; 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbonyl chloride With sodium hydroxide; tetrabutylammomium bromide In dichloromethane; water at 10 - 25℃; for 2 - 3.5h; Stage #2: With hydrogenchloride In water; acetone at 20 - 25℃; for 0.5h;
Stage #1: 1-Aminopiperidine; 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbonyl chloride With triethylamine In dichloromethane at 10 - 20℃; for 1h; Stage #2: With hydrogenchloride pH=1;	33 g
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 3 h / 0 - 20 °C 2: hydrogenchloride / diethyl ether / pH 1 View Scheme
With TEA In dichloromethane at 0 - 20℃; for 0.5h;

rimonabant (168273-06-1) → rimonabant hydrochloride (158681-13-1)

Conditions	Yield
With hydrogenchloride In methanol; water at 20℃;
With hydrogenchloride In water; acetone at 0 - 55℃; for 0.25 - 1.25h; Product distribution / selectivity;
With hydrogenchloride In methanol; butyl methyl ether at 20℃; for 2h; pH=1.0;

4'-chloropropiophenone (6285-05-8) → rimonabant hydrochloride (158681-13-1)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: triethylamine; methyl iodide / acetonitrile / 24 h / 20 - 45 °C / Inert atmosphere 2.1: tetrahydrofuran / 5 h / 10 - 20 °C 3.1: triethylamine / toluene / 12 h / 20 °C 4.1: toluene-4-sulfonic acid / toluene / 12 h / Reflux 5.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / 20 °C / Cooling with ice 6.1: triethylamine / dichloromethane / 1 h / 10 - 20 °C 6.2: pH 1 View Scheme

C17H13Cl3N2O3 → rimonabant hydrochloride (158681-13-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 12 h / Reflux 2.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / 20 °C / Cooling with ice 3.1: triethylamine / dichloromethane / 1 h / 10 - 20 °C 3.2: pH 1 View Scheme

2,4-dichlorophenyl hydrazine hydrochloride (5446-18-4) → rimonabant hydrochloride (158681-13-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine / toluene / 12 h / 20 °C 2.1: toluene-4-sulfonic acid / toluene / 12 h / Reflux 3.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / 20 °C / Cooling with ice 4.1: triethylamine / dichloromethane / 1 h / 10 - 20 °C 4.2: pH 1 View Scheme
Multi-step reaction with 3 steps 2.1: propionic acid / 16 h / Heating / reflux 2.2: 20 h / 140 - 145 °C 3.1: hydrogenchloride / water; isopropyl alcohol / 9.08 h / 10 - 20 °C View Scheme

5-(4-chlorophenyl)-4-methyl-2,3-furandione → rimonabant hydrochloride (158681-13-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine / toluene / 12 h / 20 °C 2.1: toluene-4-sulfonic acid / toluene / 12 h / Reflux 3.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / 20 °C / Cooling with ice 4.1: triethylamine / dichloromethane / 1 h / 10 - 20 °C 4.2: pH 1 View Scheme

[[1-(4-chlorophenyl)-1-propenyl]oxy]trimethylsilane → rimonabant hydrochloride (158681-13-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: tetrahydrofuran / 5 h / 10 - 20 °C 2.1: triethylamine / toluene / 12 h / 20 °C 3.1: toluene-4-sulfonic acid / toluene / 12 h / Reflux 4.1: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 2 h / 20 °C / Cooling with ice 5.1: triethylamine / dichloromethane / 1 h / 10 - 20 °C 5.2: pH 1 View Scheme

4-(4-chlorophenyl)-3-methyl-2,4-dioxobutyric acid ethyl ester (169544-41-6) → rimonabant hydrochloride (158681-13-1)

Conditions	Yield
Multi-step reaction with 3 steps 2.1: propionic acid / 16 h / Heating / reflux 2.2: 20 h / 140 - 145 °C 3.1: hydrogenchloride / water; isopropyl alcohol / 9.08 h / 10 - 20 °C View Scheme

rimonabant acid (162758-35-2) → rimonabant hydrochloride (158681-13-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / toluene / 3 h / Heating / reflux 2: triethylamine / dichloromethane / 3 h / 0 - 20 °C 3: hydrogenchloride / diethyl ether / pH 1 View Scheme

ethyl 1-(2,4-dichlorophenyl)-4-methyl-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylate (158941-22-1) → rimonabant hydrochloride (158681-13-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium hydroxide; water / methanol / 3 h / Heating / reflux 2: thionyl chloride / toluene / 3 h / Heating / reflux 3: triethylamine / dichloromethane / 3 h / 0 - 20 °C 4: hydrogenchloride / diethyl ether / pH 1 View Scheme

rimonabant hydrochloride (158681-13-1) → rimonabant (168273-06-1)

Conditions	Yield
With methanol; potassium hydroxide; water at 0 - 5℃; for 1h;	93%
With sodium hydroxide In methanol; water pH=8.5;
With sodium hydroxide In methanol; water at 28 - 30℃; for 0.666667h; pH=11;

rimonabant hydrochloride (158681-13-1) → rimonabant hydrochloride ethanolate (1000380-28-8)

Conditions	Yield
In ethanol Product distribution / selectivity; Heating / reflux;

rimonabant hydrochloride (158681-13-1) → rimonabant hydrochloride dichloromethanate

Conditions	Yield
In dichloromethane Product distribution / selectivity; Heating / reflux;

rimonabant hydrochloride (158681-13-1) → rimonabant hydrochloride hemi-isopropanolate

Conditions	Yield
In isopropyl alcohol Product distribution / selectivity; Heating / reflux;
In tetrahydrofuran; ethyl acetate; isopropyl alcohol Product distribution / selectivity; Heating / reflux;

rimonabant hydrochloride (158681-13-1) → 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)pyrazole-3-carboxamide hydrate (945634-91-3)

Conditions	Yield
With ammonia; water In methanol at 25 - 30℃; for 2h; pH=8.0 - 10.0; Product distribution / selectivity;
With water In methanol at -14 - 45℃; for 0.666667h; Product distribution / selectivity;
With water In methanol at 20 - 60℃; under 390.039 Torr; for 12h; Product distribution / selectivity; Heating / reflux;

methanol (67-56-1) + rimonabant hydrochloride (158681-13-1) → 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)pyrazole-3-carboxamide hydrate (945634-91-3) + rimonabant methanol solvate

Conditions	Yield
With water at 20℃; for 72h; Product distribution / selectivity; Heating / reflux;

Upstream product

• 2213-43-6 1-Aminopiperidine 
• 168273-05-0 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbonyl chloride 
• 63234-70-8 N-aminopiperidine hydrochloride 
• 162758-35-2 rimonabant acid 
• 168273-06-1 rimonabant 
• 158941-22-1 ethyl 1-(2,4-dichlorophenyl)-4-methyl-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylate 
• 169544-41-6 4-(4-chlorophenyl)-3-methyl-2,4-dioxobutyric acid ethyl ester 
• 5446-18-4 2,4-dichlorophenyl hydrazine hydrochloride 
• 6285-05-8 4'-chloropropiophenone 

Downstream Products

• 945634-91-3 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)pyrazole-3-carboxamide hydrate 
• 1000380-28-8 rimonabant hydrochloride ethanolate 
• 168273-06-1 rimonabant 

Relevant articles and documents

A novel and practical synthesis of rimonabant hydrochloride

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Preparation method for rimonabant hydrochloride

The invention discloses a preparation method for rimonabant hydrochloride, belonging to the field of chemical pharmacy. An ester is used as an initial raw material and undergoes hydrolysis, condensation and salt formation so as to obtain the rimonabant hydrochloride. The preparation method is simple and convenient to operate and has low cost and high yield.

PROCESS FOR PREPARATION OF PYRAZOLE DERIVATIVES

A process for preparation of Pyrazole derivatives adapted for one pot reaction involving the use of a pyclizing agent and involving the step of amidation in the presence of a catalyst. The steps for isolation and purification of found Pyrazole derivatives are also disclosed.