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

Dipolar cycloaddition of diarylnitrileimines, obtained from the reaction of Af-aryl-4-substituted benzhydrazonoyl chlorides with triethylamine, onto pyrimidines (40), afforded the corresponding l,3-diaryl-l,8a-dihydro-l,2,4-triazolo[4,3-a]pyrimidines (41) (94LA1005) (Scheme 19). 

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). 

Chlorination of thiobenzyl derivative 494 led to 557, whose reaction with aromatic amines afforded the ZV-aryl-1,2,4-triazolo[l, 5-c]pyrimidine-2-sulfonamide 558 (89EUP343752 93USP5177206). 

Thermolysis of the formamidrazone 590, obtained from the reaction of hydrazine 488 with Vilsmeier salt 589, at 200°C or on boiling in nitrobenzene led, by intramolecular transformation, to the triazolo[4,3-c]pyrimidine 591 (90T3897). Aryl isocyanide dichlorides reacted with 488 in the presence of Et2N to give 3-anilinotriazolopyrimidines (592) (Scheme 117). 

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). 

Aryl-7,8-diamino-1,2,4-triazololl, 5-c]pyrimidines (97 R= H) selectively acylate on the 8-amino group to give the amides (97 R= R CO) which cyclise on heating with PPA to yield 2-aryl-8-fIuorobenzyl-l,2,4-triazolo[5,l-/]purines (98) [94JHC1171],... 

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). 

Other claims are the isothiazolo[4,5-d][l,2,3]triazine-4-ones (170) for the treatment of gout and eschemia <86EUP274654>, the 3-aryl[l,2,5]thiadiazolo[3,4-d]pyrimidine-7-ones as antiallergics <90EUP349239>, 3-dialkylaminoethyl-l,2,3-triazolo[4,5-d]pyrimidine-5,7-diones as bronchodilators <88EUP272226>, and the 5-aryl-1,2,3-triazolo[4,5-d]pyrimidines as antihypertensives <88USP4923874>. 

Pyrazolo[4,3-d]pyrimidine and pyrazolo[3,4-d]pyrimidine sulfonamides have been synthesized as selective calcitonin inducers <02JMC2342>. A series of para-substituted 3-arylpyrazolo[3,4-d]pyrimidines have been synthesized and evaluated as inhibitors of lck kinase <02BMCL1687). The synthesis of 3-aryl-pyrazolo[4,3- f]pyrimidines as potential corticotropin-releasing factor (CRF-1) antagonists has been described <02BMCL2133>. Cyclization of 4-chloro-5-heteroimine-l,2,3-thiadiazoles furnished pyrazolo[3,4-d]pyrimidines, triazolo[4,5-d]pyrimidines and purines <02BMC449>. 

Corrosion inhibitors, [1.2,4]triazino[4,3-ojbenzimidazoles, 59, 155 Coulson-Rushbrook theorem, 55, 273 Coumarins, see l-Benzopyran-2-ones Coupling reactions, trifluoromethyl iodide with aryl halides, 60, 12 Covalent hydration in 6-nitro-l 1,2,4]triazolo[ 1,5-a)-pyrimidines, 57, 107 of coordinated ligands, 58, 138 Creutz-Taube ion, 58, 124 Criss-cross cycloadditions, of... 

Chebanov VA, Muravyova EA, Desenko SM et al (2006) Microwave-assisted three-component synthesis of 7-aryl-2-alkylthio-4, 7-dihydro-l, 2, 4-triazolo[l, 5-a]pyrimidine-... 

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). 

Flash vacuum pyrolysis of 5-aryl-tetrazoles generates aryl-carbenes, but heating the pyrimidinyl-phenyltetrazole shown below in refluxing decalin (180 °C) resnlts in the formation of an intermediate nitrene, which then cyclises onto the pyrimidine nitrogen, forming a [l,2,4]triazolo[l,5-a]-pyrimidine. ... 

The 3-arylamino-l,2,4-triazolo[4,3-c]pyrimidines 40 were regiospecifi-cally formed upon cyclization of 14 with /V-aryl phosgenimines (aryl isocyanide dichlorides). Rearrangement to the respective [1,5-c] isomers did not occur and the structure (40) was corroborated by X-ray diffraction analysis (90T3897) (Scheme 19). 

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