Pyrazoles, condensed, chemistry

Chemistry of Pyrazoles Condensed to Heteroaromatic Five- and Six-Membered Rings... 

Elnagdi, M. H., Elmoghayer, M. R. H., Sadek, K. U., Chemistry of Pyrazoles Condensed to Heteroaromatic Five- and Six-Membered Rings, 48, 223. 

Pyrazoles condensed to heteroaromatic five-and six-membered rings, 48, 223 Pyrazolopyridines, 36, 343 Pyrazolopyrimidines, chemistry of, 41, 319 Pyridazine chemistry, advances in, 49, 385 Pyridazines, 9, 211 24, 363 49, 385 Pyridine(s)... 

L. C. Behr, R. Fusco, and C. H. Jarboe, iu R. H. Wiley, ed., "Pyrazoles, Pyrazolines, PyrazoUdines, Indazoles and Condensed Rings," Vol. 22 of A. Weissberger, ed.. The Chemistry of ELetero( clic Compounds Wiley-lnterscience, New York, 1967. 

Synthesis of pyrazole 3 by the Medicinal Chemistry route was straightforward from N-Boc isonipecotic acid (45), so we utilized the route after some optimizations, as summarized in Table 2.4. The key 1,3-diketone intermediate 48 was prepared from 45 without issues. A minor problem in the original route was the exothermic nature of the Claisen condensation between methyl ketone 47 and methyl phenylacetate. Slow addition of l.lequiv of methyl phenylacetate to a mixture of 47, 0.2equiv of MeOH, and 2.5equiv of NaH in THF at room temperature solved this exothermic issue and reduced the amount of self-condensation of... 

Although only a few condensed 5 6 or 5 5 aromatic pyrazole derivatives can be isolated from biological sources, the chemistry of condensed pyrazoles has received considerable interest. Condensed pyrazoles with an indene skeleton can be considered as purine analogues and, as such, are expected to have biological activity. The discovery of the xanthene oxidase inhibitory action of pyrazolo[3,4-fiT pyrimidine and the cAMP phos-phodiasterase inhibitory action of pyrazolo[l,5-a]pyrimidines has stimulated considerable interest in the synthesis of analogues of both ring systems. 

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