Triazolopyrimidine

For the preparation of triazolopyrimidines three main types of synthesis are in use. The first of these proceeds from a pyrimidine derivative (especially the 4,5-diamino derivatives) and closes the triazole ring. The second method proceeds, on the contrary, from derivatives of u-triazole to close the pyrimidine ring. The third method finally is one which yields the derivatives through substitution or replacement of substituents in compounds prepared by one of the first-named procedures. 

Triazolopyrimidines and their derivatives are relatively stable toward alkaline and acid hydrolysis. However, the action of aqueous sodium hydroxide, ammonia, or hydrazine under pressure converts them to derivatives of 1,2,3-triazole. ... 

Tlie chemistry of one of the four possible classes of 1,2,4-triazolopyrim-idiiies, namely l,2,4-triazolo[l,5- ]pyrimidines, was reviewed in 1993 by G. Fischer [93AHC(57)81]. In two previous chapters published in this series we reviewed the chemistry of l,2,4-triazolo[4,3- ]pyrimidines [99AHC(73)131] and their [4,3-c] congeners [99AHC(75)243]. In this chapter we survey the fourth and last class of 1,2,4-triazolopyrimidines. Tlie literature has been inspected to issue number 26, Volume 129(1998) of Chemical Abstracts. 

Attempted dehydrocyclization of the 6-acylhydrazinopyrimidine 65 by heating with polyphosphoric acid led, instead, to pyrimidine ring rupture, yielding the l,l-diamino-2-nitro-2-(3-phenyl-l,2,4-triazol-5-yl)ethene 66. Cyclocondensation of the latter with triethyl orthoformate gave the fully aromatic triazolopyrimidine 67 (94JHC1171) (Scheme 23). 

Tire final chapter in the present volume is the third of a triad of reviews of 1,2,4-triazolopyrimidines, and it covers l,2,4-triazolo[l,5-c]pyrimidines. As with the first and second part of this series (which appeared in Volumes 73 and 75, respectively), it is authored by Professor M. A. E. Shaban and Dr. A. E. A. Morgaan (Alexandria University, Egypt). 

Diacetylcyclopropane reacts with 3-amino-l, 2,4-triazole in acetic acid (either aqueous or glacial) to give triazolopyrimidines 28 <%1ZV1322>, whilst a selection of fiised-ring pyrimidines, for example the l,2,3-triazolo[4,S-prepared using amino hetmoarenecarboxamides and esters <96H(42)691 >. 

The enamine 141 can be cyclized to the [l,2,4]triazolopyridopyrimidine 142 upon treatment with sodium ethoxide (Scheme 40) <2002M1297>. This fused tricyclic system may also be obtained, like the pteridine analogue (cf. Scheme 38), from the reaction of hydrazonoyl halides and pyridopyrimidines such as 143, and also by treatment of the triazolopyrimidine 144 with dimethylformamide dimethylacetal (DMF-DMA) dimethylacetal and subsequent ring closure <2003MOL333, 2003HAC491> (Scheme 41). Another series of triazolopyridopyrimidines, for example, 146, can be prepared from a hydrazine-substituted pyridopyrimidine 145, in two ways either directly by reaction with an acid chloride, or via a derived hydrazone (Scheme 42) <1996MI585>. 

It has been claimed (Scheme 46) <1997JIC624> that the [l,2,4]triazolopyrimidopyrimidines 169 and 170 can be prepared from a triazolopyrimidine (presumably 168) by reaction with carbon disulfide and formamide, respectively, although the paper contains a number of inconsistencies and inaccuracies, such that the final claim must be treated... 

Triazolopyranopyrimidines can be prepared from the phenol-substituted triazolopyrimidines. Condensation with an aldehyde with the fused dihydropyrimidine such as 181 is followed by cyclization to give benzo-fused trihetero-cyclic compounds 182 (Equation 48) <1996CHE215>. 

X-Ray studies of other types of triazolopyrimidine ring systems 679... 

In the course of elaboration of effective new synthetic routes, the compound 63 had been synthesized <1999JHC183>. X-Ray structure analysis provided a final and firm proof of the structure and, thereby, the applicability of the invented method. Rusinov et al. < 1998ZOR290> investigated the structures of the cation of salt 64 and the zwitterionic compound 65 obtained by an addition of triazolopyrimidine derivatives on A -methylpyridinium compounds. The cation 64 was found to form hydrogen-bonded dimers, whereas 65 formed a co-crystal with acetonitrile. 

In three studies, X-ray investigations of triazolopyrimidine derivatives, different from the ring system discussed above, appeared. The structures determined by crystallography are shown in Scheme 6. 

An interesting new route to derivative of this ring system was reported by Shankar and Pews <2000H(53)1151>. Triazole derivative 442 was treated first with phenyl chloroformate in the presence of triethylamine followed by reaction with phosphoms trichloride to yield the triazolopyrimidine products 443 in good yield. 

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