Pyrazole condensations

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

III. Synthesis of Pyrazoles Condensed to Five-Membered Rings. 251... 

Stanozol Stanozol, 17a-methyl-5a-androstano[3,2-c]pyrazol-17j3-ol (29.3.13), is made by reducing the double bond at C4-C5 in methyltestosterone, which has independent interest as an anabolic drug of mestanolone (29.3.11). Mestanolone undergoes formylation with ethylformate in the presence of sodium ethoxide, forming a 2-formyl (oxymethylene) derivative (29.3.12), which upon reaction with hydrazine easily cyclizes to the desired stanazole (29.3.13), which is a pyrazol-condensed steroid system [33,34]. 

Amino-l-(p-toluenesulfonyl)pyrazole condenses with -diketones to yield acylaminocrotonate derivatives. These cyclize to pyrazolo[l,5-a]pyrimidines... 

Many continuous processes are used to prepare early pharmaceutical intermediates, but Pfizer recently presented a continuous process to prepare the API itself. A continuous process to prepare the anti-inflammatory drug celecoxib was described (Scheme 11.3) [6]. The batch process for celecoxib consists of two steps (1) a base-mediated Claisen reaction between 4-methylacetophenone and ethyl trifluoroacetate, and (2) an acid-mediated pyrazole condensation between enolate intermediate 8 and hydrazine 9 giving celecoxib (Scheme 11.4) [7]. Continuously flowing the Claisen reaction step 1 into the pyrazole condensation step 2 offers the advantages of directly telescoping continuous processing steps, as described in the introduction to this chapter. 

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)... 

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