Pyrazolopyridine derivatives

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. 

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). 

New pyrazolopyridine derivatives have been synthesized <03SC253>, <03BMCL3367>, <03J1C311>. An elegant one-step synthesis of 5,6-disubstituted isoxazolo[4,5-fc]pyridine N-oxides has been carried out <03SC3077>. 

In 2013, Neres and coworker reported the synthesis, biochemical, and microbiological evaluation of a series of pyrazolopyridine derivatives as normucleoside inhibitors of BasE, an adenylating enzyme in the sidero-phore biosynthetic pathway of the opportunistic pathogen Acinetobacter baumannii. The amino-pyrazolopyridine series was produced via direct... 

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). 

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)... 

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

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. 

When a solution of 1-aminopyridinium iodide (143) in DMF was treated with anhydrous potassium carbonate, the mixture developed the deep blue color characteristic of pyridine 1-imine (144) addition of EP caused an immediate exothermic reaction giving the pyrazolopyridine 145 in 48% yield311 hydrolysis and decarboxylation gave a high yield of pyrazolo[l,5-a]pyridine (146).311 Many reactions of this type have now been carried out,312 and the regioselectivity for the cydization of 3-substituted derivatives has been examined,313... 

A practical method for the synthesis of chiral pyridazinone bearing a pyrazolopyridine ring via lipase-catalyzed resolution of 2-(acyloxymethyl)-4,5-dihydro-5-methylpyridazin-3(2H)-one derivatives 113 was reported by Yoshida et al.95... 

Acylation of a pyrazolopyridine has been shown to be temperature dependent. In the cold, benzoyl chloride and pyridine give the 2-acyl derivative (30), but at reflux the same mbcture gives the 1-acyl compound (31 Scheme 11) <73JCS(Pl)290l). 

The acid treatment of 1-aminopyridine derivatives possessing strong electron-withdrawing groups at C4 as in 97 gave pyrazolopyridines 98 Dimroth rearrangement had taken place followed by cyclization (84PJC85) (Scheme 30). 

Pyrrolopyridines 75 have been prepared by reaction of 10 with arylpyrrolidinetriones 74 k 10 has been condensed with the hydrazine derivative 76 to yield pyrazoles 77 as well as pyrazolopyridines 78, depending on the concentration of 10 used. A larger amount of 10 favoured the formation of 78. ... 

Triaza-compounds. 1,1,1,-Trifluoroacetylacetone condenses with cyano-acetylhydrazine to give a mixture of the pyridone (790) and the pyrazolopyridine (791). Thermolysis of the azide (792) leads to the rearranged pyrrolopyridaz-inone derivative (793). The complex heterocycle (796) is the unexpected product of the reaction of 4,5-diaminopyrimidine (794) with benzo-cyclobutanedione (795)/ ... 

An interesting synthesis of pyrazolopyridines has been presented by Alvarez-Builla (02S1093), using an intramolecular radical addition by the 3-pyridyl radical derived from 76a-d (Scheme 14) as well as 2-p5u-azinyl radicals to a p5uidine ring, with subsequent rearomatisation to produce cyclised products 77a-c (Scheme 17). 

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