37511-45-8

Upstream product

• 814-68-6 acryloyl chloride 
• 608-31-1 2,6-Dichloroaniline 

Downstream Products

• 86524-04-1 N-(2,6-Dichloro-phenyl)-3-(4-pyridin-2-yl-piperazin-1-yl)-propionamide 
• 1024500-32-0 5-bromo-1-(2,6-dichlorophenyl)-7-(2-hydroxyethyl)quinolin-2(1H)-one 
• 913556-82-8 1-(2,6-dichlorophenyl)-5-(2,4-difluorophenyl)-1,6-naphthyridin-2(1H)-one 6-oxide 
• 444665-44-5 1-(2,6-dichlorophenyl)-5-(2,4-difluorophenyl)-1,6-naphthyridin-2(1H)-one 
• 872973-93-8 7-chloro-1-(2,6-dichlorophenyl)-5-(2,4-difluorophenyl)-1,6-naphthyridin-2-(1H)-one 
• 916203-59-3 5-chloro-1-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-one 

Relevant academic research and scientific papers

Synthesis of a naphthyridone p38 MAP kinase inhibitor

Compound 1 is a p38 MAP kinase inhibitor potentially useful for the treatment of rheumatoid arthritis and psoriasis. A novel six-step synthesis suitable for large-scale preparation was developed in support of a drug development program at Merck Research Laboratories. The key steps include a tandem Heck-lactamization, N-oxidation, and a highly chemoselective Grignard addition of 4-(N-tert-butylpiperidinyl)-magnesium chloride to a naphthyridone N-oxide. The N-oxide exerted complete chemoselectivity via chelation in directing the Grignard addition to the α position as opposed to 1,4-addition on the enelactam. The dihydropyridyl adduct was in situ aromatized with isobutylchloroformate followed by heating in pyridine. Syntheses of Grignard precursor, N-tert-butyl-4-chloro-piperidine, were accomplished via transamination with a quaternary ammonium piperidone or via addition of methylmagnesium chloride to an iminium ion. Utilizing this chemistry, multi-kilogram preparation of compound 1 was successfully demonstrated. American Chemical Society.

Unique tandem heck-lactamization naphthyridinone ring formation between acrylanilides and halogenated pyridines

The Heck coupling of acrylanilides with 4-bromo-2-chloro-3-iodo-pyridine using palladium acetate can produce bis-Heck products or undergo an unusual tandem Heck-lactamization ring formation to generate 5-chloro-1-aryl-1,6- naphthyridin-2(1H)-ones.

Formation of acrylanilides, acrylamides, and amides directly from carboxylic acids using thionyl chloride in dimethylacetamide in the absence of bases

A general one-pot procedure is described that rapidly converts acrylic acid to anilides upon sequential treatment of the acid in dimethylacetamide (DMAC) with thionyl chloride and stoichiometric amounts of anilines in 88-98% yields, with DMAC offering rate and stability advantages over the use of DMF. The use of DMAC was extended to other organic acids in forming anilides. Benzylamine amides can also be formed using stoichiometric amounts of benzylamine and brought to completion by warming in the absence of additional base. In addition, it was shown that tert-butylamides can be easily formed with the addition of excess tert-butylamine at 20 °C.