2-Aryl-1,2,4-triazolo pyrimidines preparation

Aryl-l, 2,4-triazolo[l, 5-a]pyrimidines (17) were prepared by oxidative cyclization, by the action of lead tetraacetate (LTA), of 2-pyrimidylary-lamidines (16), first prepared by the reaction of 2-aminopyrimidines (15) with aryl cyanides in the presence of A1C13 (90SC2617) (Scheme 6). 

Cyclocondensation of aminoazoles and a,(3-unsaturated carbonyl compounds or Mannich bases is the most common method for the synthesis of dihydroa-zolopyrimidines [99, 155, 156, 157]. Various alkyl- and aryl-substituted dihy-dropyrimidines were prepared in this way. For example, cyclocondensation of 3-amino-1,2,4-triazole 147 with chalcones 148 leads to 5,7-diaryl-4,7-dihydro-l,2,4-triazolo[l,5-a]pyrimidines 149 [158], while reaction with hydrochlorides of Mannich bases 150 leads to heterocycles 151 (Scheme 3.46). 

The 2-aryl-l,2,3-triazolo[4,5-d]pyrimidines 68 were prepared by coupling diazotized p-anisidine with 4-amino-2-(dimethylamino)-6-methoxypyrimi-dine (66) to give the azo intermediate 67, which upon heating in pyridine containing CuSC>4 5H20 gave 68 (80GEP3001424) (Scheme 12). 

Due to the rapid rearrangement of the [4,3-a] series into the [1,5-a] series (see Section 4.15.4.5.2) uncontaminated [l,2,4]triazolo[4,3-a]pyrimidines are difficult to prepare. The only useful methods available (Scheme 45) seem to be treatment of an appropriate 2-hydrazinopyrimidine with a low boiling ortho ester (for 3-H, 3-Me, 3-Et and 3-Pr) or oxidative ring closure of an arylidene derivative of 2-hydrazinopyrimidine to form the 3-aryl compounds (77AJC2515). 

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