342417-04-3

Basic information

• Product Name: N-tert-butyl-6-chloro-4-(o-tolyl)nicotinamide
• Synonyms: NETUPITANT IST-2;N-?(tert-?Butyl)?-?6-?chloro-?4-?(2-?methylphenyl)?nicotinamide;3-Pyridinecarboxamide, 6-chloro-N-(1,1-dimethylethyl)-4-(2-methylphenyl)-
• CAS NO: 342417-04-3
• Molecular Formula: C₁₇H₁₉ClN₂O
• Molecular Weight: 302.79856
• EINECS: -0
• Mol File: 342417-04-3.mol

Chemical Properties

• Appearance: /
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: N-tert-butyl-6-chloro-4-(o-tolyl)nicotinamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-tert-butyl-6-chloro-4-(o-tolyl)nicotinamide(342417-04-3)
• EPA Substance Registry System: N-tert-butyl-6-chloro-4-(o-tolyl)nicotinamide(342417-04-3)

Safety Data

• Hazardous Substances Data: 342417-04-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
N-tert-butyl-6-chloro-4-(o-tolyl)nicotinamide is used as a reagent for the synthesis of NK1/NK3 receptor antagonists. These antagonists are crucial in the development of novel treatments for depression, as they can modulate the activity of neurokinin receptors, which are involved in the regulation of mood and emotional responses. By targeting these receptors, N-tert-butyl-6-chloro-4-(o-tolyl)nicotinamide-based compounds may help alleviate depressive symptoms and improve the overall quality of life for patients suffering from this condition.

Upstream product

• 115309-58-5 N-tert-butyl-6-chloro-nicotinamide 
• 33872-80-9 o-tolyl magnesium chloride 
• 84-58-2 2,3-dicyano-5,6-dichloro-p-benzoquinone 
• 1634-04-4 tert-butyl methyl ether 
• 58757-38-3 6-Chloronicotinoyl chloride 

Downstream Products

• 342417-02-1 [6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-yl]carbamic acid methyl ester 
• 342417-01-0 4-(2-methylphenyl)-6-(4-methylpiperazinyl)-3-pyridinecarboxamide 
• 342417-06-5 4-(2-methylphenyl)-6-(4-morpholinyl)-3-pyridinecarboxamide 
• 342417-07-6 [6-(morpholin-4-yl)-4-(o-tolyl)pyridin-3-yl]carbamic acid methyl ester 
• 290297-36-8 N-methyl-N-[6-(morpholin-4-yl)-4-(o-tolyl)pyridin-3-yl]amine 
• 290297-26-6 netupitant 
• 290296-68-3 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide 
• 290297-25-5 methyl-[6-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-yl]-amine 
• 881743-64-2 N-tert-butyl-6-(4-methylpiperazin-1-yl)-4-(o-tolyl)nicotinamide 
• 342417-05-4 N-tert-butyl-6-(morpholin-4-yl)-4-(o-tolyl)nicotinamide 

Relevant articles and documents

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.

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.

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 the preparation of pyridine derivatives

A process is described for preparing certain 4-alkyl- or 4-aryl-pyridine derivatives.

4-phenyl-pyridine derivatives

The compounds of the related invention are related to 4-phenyl-pyridine derivatives connected by a bridge containing oxygen or nitrogen to a phenyl derivative.