Pteridine, derivatives, preparation from

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>. 

Pteridines have been prepared in good yields from 6-amino-5-nitrosouracils with Meldrum s acid in the presence of piperidine as catalyst under thermolytic conditions <06SC3085>. Novel 6-formylpterin derivatives have been synthesized and their neuroprotective effects studied <06OBC1811>. 

Although pteridines can be made from pyrazines, it is usually much easier to prepare them from 4,5-pyrimidinediamines or the like.1689 Since many pteridines can be easily degraded to pyrazines, this process offers a practical primary synthetic route to a variety of pyrazine derivatives. However, in comparison with more than 150 examples cited by Barlin from pre-1978 literature,1686 recent use of the method has been modest. Typical examples follow ... 

Replacement of carbon by nitrogen at position 8 of the pteridine ring in MTX and AMT has been accomplished by Srinivasan and Broom [36]. Starting from 6-bromomethylpyrido[3,2-rf]pyrimidine-2,4(lf/,3/f)-dione (III. 115), the xV-oxide was prepared by w-chloroperbenzoic acid oxidation and subjected to Polonovski rearrangement (AcjO-AcOH) to obtain the 6-acetoxymethyl derivative (III.116). Treatment of (III.116) with POCI3 afforded the 2,4-dichloro derivative (III.117), which on being heated at 160-170 °C in liquid ammonia in a pressure vessel was converted to the... 

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