Pyrazolopyridines

Pyrazolopyridines isomeric to those described previously have been obtained by other methods. Thus, the derivative (558) was formed by Raney nickel reduction of the 4-nitrosopyrazole (557) (7UHC1035), and the pyrazolo[3,4-c]pyridine derivative (560) was prepared from the azide (559) (79CC627). 

Pyrazolo[l,5-a]pyridine-2,3-dicarboxylic acid dimethyl ester synthesis, 5, 153 Pyrazolopyridines acylation, 5, 311 6-fused... 

The imine (161), obtained from 1-aminopyridinium iodide and potassium carbonate, combines with dimethyl acetylenedicarboxylate yielding in the first place (162) which then with more ester gives dimethyl fumarate and the pyrazolopyridine (163), isolated in 15% yield. A corresponding reaction with isoquinoline imine gave 75% of the primary adduct [(cf. (162)]. ... 

With a change to non-polar solvent, the reaction of ylides 269 with alkynes and alkenes changed dramatically, as shown in Scheme 10. With DM AD in toluene the ylides give pyrazolopyridines 272 in good yield (91TL4977), and with methyl propiolate (MEP) give indolizines 273 (92H(33)203). The reaction with acrylates is much less clean, but the variety of products is said to be formed from a diazene intermediate, which splits to give a diradical (93H(35)851). 

The ylides 276 derived from compound 2 undergo ring opening on thermolysis to give 2-pyridylcyanamides (Section IV.F), and react with acetylenic esters to give pyrazolopyridines (Scheme 12) (86H(24)2563). In the addition of DMAD some intermediate dihydro derivative is obtained and dehydrogenated with chlo-ranll. An ylide of system 3 is used as a catalyst (Section IV.J)... 

Ketene dithioacetal 130 reacts with 3-amino-2-pyrazolin-5-one 129 to give the highly functionalized pyrazolopyridine 131, which is converted into the bispyrazolopyridine 132 by reaction with hydrazine hydrate (Scheme 9) <1997JCM256>. 

Similarly, Yli-Kauhaluoma and co-workers have studied the 1,3-dipolar cycloaddition of polymer-bound alkynes to azomethine imines, generated in situ from A-ami nopyridine iodides, in the synthesis of pyrazolopyridines <06JCC344>. 

The ring transformation of the fused triazolium salt 133 to the pyrazolopyridine derivative 134 proceeds via ring opening according to a valence-bond isomerization <1999JOC5499> and was already discussed in Section 11.16.5.1. 

In previous work (85MI1 87AHC319), the synthesis and chemistry of pyrazolopyridines and pyrazolopyrimidines was surveyed. This chapter reports synthetic approaches to other aromatic 10 tt electron systems containing a pyrazole moiety, as well as the systems main chemical and physicochemical properties. 

Scheme 15 Synthesis of positional isomers of pyrazolopyridine carboxylic acid derivatives...

Hantzsch-type reaction between 5-amino-3-methyl-l-phenylpyrazole, 4-dimethyl-aminobenzaldehyde, and 2-aroylbenzimidazole is followed by elimination of 4-dimethylaminophelyl substituent [75]. The treatments that were carried out in boiling glacial acetic acids for 2 h yielded pyrazolopyridines 44 when Ry 4-NO2C6H4 (Scheme 19). 

As shown in Scheme 8.67, the cyclization of diazoalkenes 273 requires thermal activation and not only affords 3/7-pyrazoles 274, but also cyclopropenes 275 that are formed from carbene intermediates (319). The activation parameters for cyclopropene formation (i.e., N2 elimination from 273) have been determined (320). A novel example involves the cyclization of the 3-nitro-l-diazoprop-2-ene derivative 276 into pyrazolopyridine derivative 277 (45). 

Condensation of the intermediates 146-151 with either ethyl 5-amino-l-methylpyrazole-4-carboxylate or ethyl 2-aminothiophene-3-carboxylate using sodium hydride in refluxing dioxane gave the corresponding 4-hydroxy-l-methyl-pyrazolopyridine or 4-hydroxythienylpyridine esters, respectively (Equation 52 Table 28) <2003BMC2991>. 

The pyrazolopyridines comprise five isomers (1-5), derivatives of which were first reported in 1906,1 1934,2 1906,3 1958,4 and 1957,5 respectively. Pyrazolopyridines have continued to attract interest because of their biological activity and structural relationship to indoles6 and azaindoles (pyrrolopyridines).7 Pratap8 published a brief outline of synthetic routes to derivatives of 1 and 3 but the subject has not been comprehensively reviewed. 

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