1.2.4- Triazolo pyrimidin-5 -thiones

Sulfurization of l-(2,3,5-tri-0-acetyl-j8-D-ribofuranosyl)-l, 2,4-triazolo [4,3-a]pyrimidin-5-one (149) with phosphorus pentasulfide gave the 1-(2,3,5-tri-0-acetyl-/3-D-ribofuranosyl)-l,2,4-triazolo[4,3-a]pyrinidin-5-thione 150 (78MI1) (Scheme 60). 

Formation of l,2,4-triazolo[l,5-c]pyrimidine-5(6//)-thiones or their 5(6//)-ones by the reaction of l,4,6-triaminopyrimidine-2(l//)-thiones (468) with the Vilsmeier reagent has been found to be dependent on the temperature. Thus, treatment of 468 with phosphoryl chloride and DMF at 0-5°C afforded mainly the thiadiazolopyrimidinium chloride 470 in addition to the thione 471, but at 25°C a mixture of 471 and 7-formamido-l,2,... 

Synthesis of 9-substituted tetrahydroazepinopurines as asmarine analogs has been described <03T6493>. In relation to adenosine receptor antagonists, new derivatives of pyrazolo[4,3-c][l,2,4]triazolo[l,5-c]pyrimidines have been synthesized <03IMC1229, 4287>. A one-pot synthesis of l,2,4-triazolo[l,5-c]quinazoline thiones 65, consisting of a domino cyclization of 2-isothiocyanatobenzonitrile 63 with hydrazides 64 has been published <03EJO182>. 

A derivative of a hitherto unknown nucleus was produced when 4-amino-5-aminomethyl-3-methyltriazole was refluxed with carbon disulfide and triethylamine in pyridine, which yielded 3-methyl-3,7-dihydro-l,2,3-triazolo-[4,5-d][l,3]thiazine-5-thione (98) (3 hr, 53%) the 3-benzyl analog was made similarly (63%) [80JCS(P1)2009]. Cyclization of 4-anilino-5-ethoxycarbonyltriazole with polyphosphoric acid produced 1 f/-triazolo-[4,5-h]quinol-4-one (99) [80EUP(A)2562]. Similarly, ring closure of 4-(2-pyridylamino)triazole-5-carboxylic acid (or its esters) gave l//-pyrido-[l,2-a]-l,2,3-triazolo[4,5-d]pyrimidin-4-one (100) (77GEP2757929). 4-Amino-5-formyl-3-methyltriazole and pentane-2,4-dione, set aside in 20% sulfuric acid, yielded 3,5-dimethyl-3//-l,2,3-triazolo [4,5-6] pyridin-6-yl... 

Yet another type of isomer formation has been discovered, the formation of a 1,2-dihydro-l,2,4-triazolo[l,5-a]pyrimidine-2-thione (XLVIII) from 2,3 - dihydro-1,2,4-triazolo[4,3-a]pj rimidine-3-thione (XLVII) during the cyclizations of carbon disulfide with 2-hydrazino-pyrimidine, 2-hydrazino-4-methylpyrimidine and 2-hydrazino-4.6-di-methylpyrimidine 316, 320). 

These isomers (XLVIII) are formed as side-products during the cycUzation reaction or when the 2,3-dihydro-l,2,4-triazolo[4,3-a]pyri-midine-3-thiones (XLVII) are heated either in water or water-pyridine mixtures. These isomerisations are probably proceeded by the hydrolysis of the (XLVII) first formed. The hydrolysis likely yields either the Schiff s base of 5-amino-2l4-l,2,4-triazoline-3-thione (XLIXa) or 5-amino-zl4-l,2,4-triazoline-3-thione (XLIXb) and the corresponding -dicarbonyl compound. These substances can now cyclize again either on the Nj or the nitrogen atom. This re-cyclization however will occur most readily on the more nucleophile nitrogen atom of the hydrazino function (Nj). Similar conversion reactions are known and have been studied in detail for the non-thioxo substituted l,2,4-triazolo[4,3-a] pyrimidines 3, 317, 318, 319, 383). 

Still another isomer, the 5-hydroxy-7-methyl-2,3-dihydro-l,2,4-triazolo[4,3-c]pyrimidine-3-thione (LI) is formed in the reaction of... 

Since specificity of the nucleoside phosphorylases varies, enzymes that catalyze the formation of the nucleosides of the so-called fraudulent purine bases, 6-mercaptopurine (purine-6(lH)-thione) and 8-aza-guanine (5-amino-t -triazolo[ 4,5-d]pyrimidin-7(6if)-one), have been found, and gram quantities of 8-azaguanosine have been isolated. ... 

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