342417-01-0

Basic information

• Product Name: 3-PYRIDINECARBOXAMIDE, 4-(2-METHYLPHENYL)-6-(4-METHYL-1-PIPERAZINYL)-
• Synonyms: 6-(4-METHYLPIPERAZIN-1-YL)-4-O-TOLYLNICOTINAMIDE;4-(2-Methylphenyl)-6-(4-methyl-1-piperazinyl)-3-pyridinecarboxamide;6-(4-Methylpiperazin-1-yl)-4-(2-methylphenyl)nicotinamide;4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide;3-PYRIDINECARBOXAMIDE, 4-(2-METHYLPHENYL)-6-(4-METHYL-1-PIPERAZINYL)-C32;4-(2-methylphenyl)-6-(4-methylpiperazinyl)-3-pyridinecarboxamide;3-PYRIDINECARBOXAMIDE, 4-(2-METHYLPHENYL)-6-(4-METHYL-1-PIPERAZINYL)-
• CAS NO: 342417-01-0
• Molecular Formula: C₁₈H₂₂N₄O
• Molecular Weight: 310.39
• Mol File: 342417-01-0.mol

Chemical Properties

• Melting Point: 164-165℃
• Boiling Point: 498.1°C at 760 mmHg
• Flash Point: 255°C
• Appearance: /
• Density: 1.165
• Vapor Pressure: 4.67E-10mmHg at 25°C
• Refractive Index: 1.6
• Storage Temp.: 2-8°C
• PKA: 15.82±0.50(Predicted)
• CAS DataBase Reference: 3-PYRIDINECARBOXAMIDE, 4-(2-METHYLPHENYL)-6-(4-METHYL-1-PIPERAZINYL)-(CAS DataBase Reference)
• NIST Chemistry Reference: 3-PYRIDINECARBOXAMIDE, 4-(2-METHYLPHENYL)-6-(4-METHYL-1-PIPERAZINYL)-(342417-01-0)
• EPA Substance Registry System: 3-PYRIDINECARBOXAMIDE, 4-(2-METHYLPHENYL)-6-(4-METHYL-1-PIPERAZINYL)-(342417-01-0)

Safety Data

• Hazardous Substances Data: 342417-01-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-Pyridinecarboxamide, 4-(2-methylphenyl)-6-(4-methyl-1-piperazinyl)is used as an antidepressant medication for the treatment of depression, leveraging its ability to increase serotonin levels in the brain, which contributes to mood improvement.
3-Pyridinecarboxamide, 4-(2-methylphenyl)-6-(4-methyl-1-piperazinyl)is also used as an anxiolytic agent for managing anxiety disorders, capitalizing on its capacity to reduce anxiety levels.
Furthermore, it is used as a sedative for the treatment of insomnia, taking advantage of its sleep-inducing properties to help patients achieve restful sleep.
3-Pyridinecarboxamide, 4-(2-methylphenyl)-6-(4-methyl-1-piperazinyl)is utilized as an alternative to traditional antidepressants due to its fewer side effects and lower risk of dependence, offering a safer treatment option for patients with mood disorders.

InChI:InChI=1/C18H22N4O/c1-13-5-3-4-6-14(13)15-11-17(20-12-16(15)18(19)23)22-9-7-21(2)8-10-22/h3-6,11-12H,7-10H2,1-2H3,(H2,19,23)

Upstream product

• 109-01-3 1-methyl-piperazine 
• 342417-00-9 6-chloro-4-(o-tolyl)nicotinamide 
• 881743-64-2 N-tert-butyl-6-(4-methylpiperazin-1-yl)-4-(o-tolyl)nicotinamide 
• 115309-58-5 N-tert-butyl-6-chloro-nicotinamide 
• 342416-99-3 6-chloro-4-o-tolyl-nicotinic acid 
• 342417-04-3 N-tert-butyl-6-chloro-4-(o-tolyl)nicotinamide 
• 58757-38-3 6-Chloronicotinoyl chloride 
• 5326-23-8 6-Chloro-3-pyridinecarboxylic acid 
• 529-20-4 2-methylphenyl aldehyde 
• 70625-63-7 methyl 2-cyano-3-(2-methylphenyl)-2-propenoate 
• 33252-28-7 6-chloronicotinonitrile 
• 873443-66-4 3-cyano-2,6-dichloro-4-(2-methylphenyl)pyridine 
• 33872-80-9 o-tolyl magnesium chloride 

Downstream Products

• 342417-02-1 [6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-yl]carbamic acid methyl ester 
• 290297-25-5 methyl-[6-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-yl]-amine 
• 290297-26-6 netupitant 
• 290297-24-4 6-(4-methyl-piperazin-1-yl)-4-o-tolylpyridin-3-yl-amine 
• 1431216-61-3 1-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-4-methylpiperazine 1,4-dioxide 
• 1431216-59-9 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium 
• 1431216-68-0 4-(5-{2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethylpropanamido}-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-{[bis(tert-butoxy)phosphoryl]oxymethyl}piperazin-1-ium 

Relevant articles and documents

Synthesis method of 6-(4-methylpiperazine-1-yl)-4-o-tolyl nicotinamide

The invention discloses a synthesis method of 6-(4-methylpiperazine-1-yl)-4-o-tolyl nicotinamide, which comprises the following steps: (1) taking 6-chloronicotinonitrile as an initial raw material, carrying out nucleophilic addition reaction on the initial raw material and a reagent A in the presence of a boron trifluoride reagent, and after the reaction is completed, adding an oxidizing agent to carry out oxidation reaction to obtain a compound (II); the reagent A is o-tolyl magnesium halide or a combination of o-tolyl magnesium halide and lithium chloride; (2) condensing the compound (II) and N-methyl piperazine to generate a compound (III); (3) carrying out hydrolysis reaction on the compound (III) and hydrogen peroxide under the action of alkali to generate a compound (IV); the method is simple in reaction route, mild in reaction condition, high in product yield and suitable for industrial production.

NK1 receptor-targeting antagonist and application of same to chemotherapy-induced nausea and vomiting

The invention relates to a NK1 receptor-targeting antagonist and application of the same to chemotherapy-induced nausea and vomiting, belonging to the technical field of adjuvant therapeutics for tumor chemotherapy. The invention provides a compound as shown in a formula I which is described in the specification, or a racemate, stereoisomer, tautomer, isotopic label, oxynitride or pharmaceutically-acceptable salt thereof. The invention also provides a preparation method for the compound, a pharmaceutical compositions and the application of the compound or the racemate, stereoisomer, tautomer,isotopic label, oxynitride or pharmaceutically-acceptable salt thereof.

4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium as a neurokinin receptor modulator

Compounds and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor, based on 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)3yridine-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium and pharmaceutically acceptable salts thereof.

SUBSTITUTED 4-PHENYL-PYRIDINES FOR TREATMENT OF NK-1 RECEPTOR RELATED DISEASES

PROBLEM TO BE SOLVED: To provide new derivatives of 4-phenyl-pyridine compounds that are effective NK1 receptor antagonists, with enhanced physicochemical and/or biological properties, and methods for producing the 4-phenyl-pyridine compounds. SOLUTION: Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NKj) receptor. The compounds have the general formula (I). COPYRIGHT: (C)2015,JPOandINPIT

Substituted 4-phenyl pyridines having anti-emetic effect

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor. The compounds have the general formula (I):

Research and development of an efficient process for the construction of the 2,4,5-substituted pyridines of NK-1 receptor antagonists

Roche has identified a 2,4,5-trisubstituted pyridine template for a new class of potent NK1 receptor antagonists. Previous strategies for construction of the pyridine core of these NK-1 receptor antagonists involved functionalization of a 2,5-disubstituted pyridine. We now report on construction of the pyridine core from commodity components. Shestopalov reported the synthesis of trans-4′-aryl-5′-cyano-1′,2′,3′, 4′-tetrahydro-6′-hydroxy-2′-oxo-1,3′-bipyridinium inner salts from 1-(2-amino-2-oxo-ethyl)pyridinium chloride, aromatic aldehydes, and ethyl cyanoacetate in the presence of a base. Reaction of these salts with phosphorus oxychloride affords 4-aryl-3-cyano-2,6-dichloropyridines. These are efficiently converted to nicotinamide precursors of the Roche NK-1 receptor antagonists by regioselective displacement of one chlorine by an amine, hydrogenolysis of the remaining chlorine, and nitrile hydrolysis.

Process for preparation of pyridine derivatives of NK-1 receptor antagonist

The present invention provides a process for preparing a pyridine compound of the formula: wherein R1, R2, R3 and a are those defined herein.

Efficient synthesis of novel NK1 receptor antagonists: Selective 1,4-addition of Grignard reagents to 6-chloronicotinic acid derivatives

A new efficient synthesis of two novel classes of NK1 receptor antagonists, among them befetupitant and netupitant, starting from 6-chloronicotinic acid is described. The introduction of the o-tolyl substituent at C(4) of the pyridine ring was achieved by a one-pot selective 1,4-Grignard addition/oxidation sequence to 6-chloronicotinic acid or a derivative of it. The scope of this addition/oxidation sequence was examined. It was also shown that the carboxylic function can be converted to a methyl amino group by a Hofmann rearrangement followed by reduction. Furthermore, a new high-yielding synthesis of 2-(3,5-bistrifluoromethylphenyl)-2-methyl propionic acid based on the carbonylation of the tertiary alcohol obtained by Grignard addition of 3,5-bis(trifluoromethyl)bromobenzene to acetone was established.

Process for preparation of pyridine derivatives

The present invention relates to a process for the manufacture of compounds of formula wherein the substituents are as described herein which comprises the steps of a) reacting a compound of formula with a compound of formula to form a compound of formula b) converting the OH/═O function of compounds of formula XIV/XIVa into a leaving group P with a reagent containing a leaving group, selected from POCl3, PBr3, MeI and (F3CSO2)2O to form a compound of formula wherein P is halogen or trifluoromethanesulfonate; c) substituting R2 for the leaving group P by reacting compound XV with HR2 to form a compound of formula and d) hydrolyzing the nitrile function in an acidic medium selected from H2SO4, HCl and acetic acid, to form a compound of formula I The compounds of formula I are valuable intermediates for the manufacture of therapeutically active compounds which have NK-1 antagonist activity.