Pyrazole ring construction

Stereoselective 1,3-dipolar cycloaddition of the azomethine imine 283, obtained by reacting acetaldehyde and the dihydropyrazolo[4,3-d]-pyridazin-4-one 282, with the acetylenic derivative 284 resulted in the construction of the second fused pyrazole ring of 285. Condensation of 282 with the dialdoglucopyranose 286 instead of acetaldehyde gave the aldose azomethine imine 287, which added 284 to give the C-nucleoside 288 carrying two carbohydrate moieties (93FA231) (Scheme 87). 

Scheme 12.4 shows an example of the construction of the pyrazole ring by [2 + 3] cycloaddition via route B. Celecoxib 24 is synthesized in 70% yield by a condensation-cyclization sequence. ... 

Similarly, for the construction of a central imidazolinone core skeleton of rhopaladin D, a marine alkaloid, the PS-BEMP promoted aza-Wittig reaction followed by intramolecular cyclization was used [64], and a tetrasubstituted pyrazole ring of sildenafil... 

Construction of Isoxazole, Pyrazole and Pyrimidine Rings from Aminopropenones... 

JME696>. Construction of the five-membered ring is also the key step in the synthesis of the pyrazole- and isoxazole-fused pyridopyrimidines 470 (Equation 198) <2004HC089>. 

Pyrazole 1131 was prepared from the mesylate 1130, which proved to be an excellent precursor for this type of nucleoside as in 1132. The construction of the pyrimidine ring was achieved through the steps shown in Scheme 220 to give 1133 and 1134 [85JCS(P1)1425 89JCS(P1)925]. 

The construction of a heterocyclic ring from two reagents, one of which contains a nitro group, is widely used in the synthesis of the nitro derivatives of pyrazole, isoxazole, and 1,2,3-triazole. Thus, for example, the reaction of sodionitromalonal-dehyde with substituted hydrazines leads to the corresponding derivatives of 4-nitropyrazole [33, 61, 471 173] (Scheme 63). 

Ring aromaticity (and antiaromaticity) presumably influence the selectivity of closure. The construction of certain heterocycles, e.g. pyrazoles, isoxazoles, etc., may be rationalized in this way (equation 70). Indeed, it may be the driving force which... 

An additional heterocyclic ring fused to a (6 5 6) system can be constructed by a cyclocondensation reaction of an appropriately substituted tricyclic derivative with an external reagent. The NH2-CN functionality of (177) was transformed into a pyrimidine by the reaction with formamide <91H(32)895>, and cyclocondensation of the Ac-OH functionality in (178) with phenyl-hydrazine gave a pyrazole <9lH(32)90l>. A hydrazino derivative (179) was condensed with a carboxylic acid to give a 1,2,4-triazole in the reaction that involves an N-2 atom of (179) <88Ci(L)785>. 

More recently, to find more effective methods to construct bis(heterocycle)s containing a pyrimidine ring from MBH derivatives, the solid-phase parallel synthesis of new annulated pyrimidinone derivatives was disclosed (Scheme 4.219). " The resin-bound allyl amine derivatives 742 were treated with cyanogen bromide to yield the pyrazole derivatives 743 in good yields under standard conditions. The subsequent lactonization with cleavage of the resin afforded the pyrimidinone derivative 744 in good yields in the presence of 20% triethylamine in chloroform under reflux. 

The construction of two heterocyclic rings in one S)mthetic step has been developed for the preparation of coumarin derivatives. In this process, the thiazole ring (31 - 40) is accomplished by Flantzsch reaction monitored by fabrication of pyrazole by reacting a 3-(2-bromoacetyl) coumarin with thiosemicarbazide and acetylacetone at room temperature [87]. 

Formycin has been prepared by constructing the pyrimidine ring from a 4-nitro-pyrazole-C-nucleoside precursor. Diels-Alder reactions have been used in a synthesis of DL-showdomycin (21) via the adduct (22) outlined in Scheme... 

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