5-Triazolo pyrimidine

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>. 

Triazolopyrimidine, Triazolo[l, 5-a]pyrimidine, Triazolo[l, 5-c]pyrimidine. Sulfonamide, Penoxsulam... 

The fusion name l//-triazolo[4,5-d]pyrimidine for (140) is preferred by practitioners in the field and appears in CA indexes. On the other hand, the nonspecialist, who may well be uncertain about his command of fusion nomenclature, might more easily grasp the replacement name l//-l,2,3,4,6-pentaazaindene. (This is an appropriate place to emphasize that, by lUPAC rules, replacement names are to be based only on a completely carbocyclic parent. Notwithstanding the attractive simplicity of 8-azapurine for the example at hand, it has no sanction see, however. Section 1.02.3.2. The purpose of this avoidance is to forestall a multiplicity of names for systems containing several hetero atoms.)... 

Amino-l,2,4-triazole undergoes a cyclocondensation with 3-etlioxyacrolein (7) to form 1,2,4-triazolo[l,5-a]pyrimidine (3) or its [4,3-u] isomer (5), according to whether it reacts as IH or 4H tautomer 2 or 4. Moreover, the pyrimidines 3 and 5 can interconvert by a Dimroth rearrangement. Since the H NMR spectrum 30a does not enable a clear distinction to be made AMX systems for... 

The formal derivation of the analogs, described in the foregoing, represents, from the point of view of systematic organic chemistry, a shift to the derivatives of other heterocyclic systems. In the case of pyrimidine aza analogs we arc dealing with derivatives of symmetrical or asymmetrical triazine in the case of purine aza analogs, the derivatives produced are those of imidazo[4,5]-i -triazine and z -triazolo [4,5-d] pyrimidine. 

According to the systematic nomenclature these substances were first named l-f-triazolo[d] pyrimidines in compliance with the general principles of the Ring Index/ More recent papers and Chemical Abstracts indexes use the term i -triazolo[4,5-d]pyrimidine (147) in accord with the lUPAC nomenclature. The numbering of substituents when using the last-mentioned name is different from that of the 8-aza analogs. For the formulas of oxygen and sulfur derivatives names derived from the lactim or thiolactim form are almost exclusively in use (in common with the purine derivatives). These derivatives are thus described as hydroxy and mercapto derivatives, respectively. The name 1,2,3,4,6-pentaazaindene is used only rarely for this system. 

The 8-aza analogs of purine bases were the first to be studied among all the aza analogs of nucleic acid bases (as early as 1945). Before that time the chemistry of these substances had not been treated in detail from any aspect. Thus the entire chemistry of the u-triazolo [4,5-d]pyrimidines was developed only in connection with the study of antimetabolites of nucleic acid components. Therefore all the papers involved are largely of preparative character and only rarely discuss. theoretical points. 

Another synthesis of -triazolo [4,5-d] pyrimidines described first by Benson et and by Hartzel and Benson also involves closing... 

A combination of the preceding type of synthesis and of cyclization of 4-amino-5-arylazopyrimidine can be seen in the novel procedure of Richter and Taylor. Proceeding from phenylazomalonamide-amidine hydrochloride (180), they actually close both rings in this synthesis. The pyrimidine ring (183) is closed by formamide, the triazole (181) one by oxidative cyclization in the presence of cupric sulfate. Both possible sequences of cyclization were used. The synthetic possibilities of this procedure follow from the combination of the two parts. The synthesis was used for 7-substituted 2-phenyl-l,2,3-triazolo[4,5-d]-pyrimidines (184, 185). An analogous procedure was employed to prepare the 7-amino derivatives (188) from phenylazomalondiamidine (186). 

The examples in the fourth column (Table IX) concern the protonation of purine and adenine and their derivatives while those of the last column mainly reflect Kleinpeter s contributions (Table VIII) to the functional tau-tomerism of 7-hydroxy-l,2,4-triazolo[l,5-a]pyrimidines. 

Simple examples of diazoalkylideneamine-l,2,3-triazole equilibria have been demonstrated for a series of l,2,3-triazolo[l,5-a]pyrimidines by variable-temperature NMR [74JCS(CC)671]. Tautomers A, B, and C interconvert rapidly at elevated temperatures the energy barrier for these ring-opening-ring closure processes was found to be AG = 76 kJ mol (for = H, Me R = CONH2) (Scheme 111). 

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