title: Microwave-assisted and continuous flow multistep synthesis of 4-(pyrazol-1-yl)carboxanilides.
abstract: A series of 4-(pyrazol-1-yl)carboxanilides active as inhibitors of canonical transient receptor potential channels were synthesized in an efficient three-step protocol using controlled microwave heating. The general synthetic strategy involves condensation of 4-nitrophenylhydrazine with appropriate 1,3-dicarbonyl building blocks, followed by reduction of the nitro group to the amine, which is then amidated with carboxylic acids. Compared to the conventional protocol a dramatic reduction in overall processing time from ~2 days to a few minutes was achieved, accompanied by significantly improved product yields. In addition, the first two steps in the synthetic pathway were also performed under continuous flow conditions providing similar isolated product yields. As an alternative to the three-step protocol, a novel two-step route to the desired 4-(pyrazol-1-yl)carboxanilides was devised involving condensation of 4-bromophenylhydrazine with appropriate 1,3-dicarbonyl building blocks, followed by Pd-catalyzed Buchwald-Hartwig amidation with carboxylic acid amides.
authors: Christian Doppler Laboratory for Microwave Chemistry (CDLMC) and Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
authors: David
authors: D
authors: Obermayer
authors: Toma N
authors: TN
authors: Glasnov
authors: C Oliver
authors: CO
authors: Kappe
mesh_terms: D000577:Amides / Q000737:chemistry*; D002261:Carboxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D006361:Heating; D008872:Microwaves; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000577:Amides; D011720:Pyrazoles; C031280:pyrazole; D002261:Carboxin