Pyrazole-5-carboxamides

A rapid and high yielding synthesis of pyrazolo[3,4- pyrimidinones by reaction of aromatic aldehydes with 4-amino-l-methyl-3-propyl-177-pyrazole-5-carboxamide intermediates in the presence of copper chloride has recently been reported for the synthesis of Viagra analogues <2005H(65)1821>. 

Animals. Metabolite is A/-[4-(l-hydroxymethyl-1 -methyl -ethyl) benzyl]-4-chloro-3-( 1 -hydroxyethyl)-1 -methyl-pyrazole-5-carboxamide Plants. As for animals... 

Bromo-N-[4-chloro-2-methyl-6-[(methylamino)Carbonyl]Phenyl]-l-(3-chloro-2-pyridinyl)-1H- pyrazole-5-carboxamide... 

Chloro-AM[4-(l,l-dimethylethyl)Phenyl]Methyl 3-ethyl-l-methyl-ltf-pyrazole-5-carboxamide Structure 4.149... 

Mutlib, A. et al., Formation of unusual glutamate conjugates of l-[3-(aminomethyl) phenyl]-/V-[3-fluoro-2 -(methylsulfonyl)-[l,l -biphenyl]-4-yl]-3-(trifluoromethyl)-lH-pyrazole-5-carboxamide (DPC 423) and its analogs the role of gamma-glutamyltrans-peptidase in the biotransformation of benzylamines, Drug Metab. Dispos., 29 (10), 1296, 2001. 

Quan, M.L., et al. Discovery ofl-(3 -Aminobenzisoxazol-5 -yl)-3-trifluoromethyl-A-[2-fluoro-4-[(2 -dimethy-laminomethyl)imidazol-l-yl]phenyl-lF7-pyrazole-5-carboxamide Hydrochloride (Razaxaban), a highly potent, selective, and orally bioavailable factor Xa inhibitor. J. Med. Chem. 2005, 48, 1729-1744. 

In a stage of the synthesis, 4-(2-ethoxybenzamido)-l-methyl-3-propyl-pyrazole-5-carboxamide was chlorosulfonated by reaction with chlorosulfonic acid-thionyl chloride (18 hours) to yield 4-ethoxy-3-(5-aminocarbonyl-l-methyl-3-propylp5n-azol-4-yl) carbamoylbenzenesulfonyl chloride. In this reaction, sulfonation occurs preferentially para with respect to the more powerful electron-donating ethoxy group as would be anticipated (Chapter 6, Section 1.2.4). 

Parlow et al. [23] used supported reagents and scavengers in two approaches to the optimisation of a lead pyrazole-5-carboxamide (Figure 9) investigating... 

Figure 9. Pyrazole-5-carboxamide optimised by parallel synthesis.

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