342417-03-2

Upstream product

• 5326-23-8 6-Chloro-3-pyridinecarboxylic acid 
• 58757-38-3 6-Chloronicotinoyl chloride 
• 224817-12-3 6-chloronicotinic acid benzylamide 
• 33872-80-9 o-tolyl magnesium chloride 

Downstream Products

• 342416-86-8 N-benzyl-6-(morpholin-4-yl)-4-(o-tolyl)nicotinamide 
• 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 
• 290296-68-3 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide 

Relevant academic research and scientific papers

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.