Triazolo pyridine ring synthesis

Reaction of 201 with 1,3-dicarbonyl compounds, or with aliphatic and cyclic ketones 203 in the presence of dilute sulfuric acid, gave the 3//-l,2,3-triazolo[4,5-6]pyridines 204 (79CPB2861). The mechanism of transformation involves ring fission to 202, followed by reaction with 203 to give 204, a type of Friedlaender synthesis (see Scheme 42). 

The [l,2,4]triazolo[l,5- ]pyridine system is usually constructed by the closure of the triazole ring either by oxidative formation of the NN bond or by condensation of the N-aminopyridine derivatives . Various compounds 78 were obtained by the oxidation of the amidine 77 with Mn02 (Scheme 47) <2003IJB2901, 2005ARK(xiii)21>. A dehydrative cyclization by treatment of formamidoximes 79 with trifluoroacetic anhydride (TFAA) has been used in the synthesis of 80 (Scheme 48), which are key building blocks in the preparation of DPP (IV) inhibitors <2005EJ03761, 2006JME3614>. 

Several unique heterocyclic fused-1,2,4-triazole structures have been published. Pyridine amination of 216 with O-mesitylenesulfonylhydroxylamine followed by condensation with various aryl and heterocyclic aldehydes and subsequent cyclization and oxidation gave triazolopyridines 217 <03TL1675>. Triazolopyridines 217 were utilized in the direct conversion to the triazolopyridine amides 218 with methylaluminoxane premixed with amines in a combinatorial library synthesis. A convenient synthesis of novel 4-(l,2,4-triazol-l-yl)-2-pyrazolines and their derivatives has been reported <03SC1449>. A novel triheterocyclic ring system, thieno[2,3-y][l,2,4]triazolo[l,5-a]azepines, has been published <03S1231>. 

In addition to those 6- and 8-substituted [4,3-n] systems mentioned previously in the Dimroth rearrangement discussion, a variety of 5-substituted derivatives has been described (78JHC439) from ring closure of 6-chloro-2-hydrazinopyridine (see synthesis section). A useful material obtained from this investigation was 5-chloro-[l,2,4]triazolo[4,3-n]pyridine (102) which was susceptible to nucleophilic substitution by strong nucleophiles (sodium... 

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