1.2.4- Triazolo pyrimidin-2-ones, reaction

The reaction of S-alkylated compound 81 with diazotized anilines proceeded via a one pot tandem Japp-Klingemann, Smiles rearrangement and cyclization reactions to afford triazolo-pyrimidines 82. ° The reaction of 83 and 84 were also studied using this tandem protocol,... 

Isothiocyanato-3,3-dimethylbutan-2-one (87) provided the C4N3 fragment that gave, upon reaction with 2-ethylthiosemicarbazide (CN3 fragment) (88), the 3-ethyl-l,6,7,8a-tetrahydro-2,5-dithioxo-8,8,8a-trimethyl-l,2,4-triazolo[l,5-c]pyrimidine 89 (76M1241) (Scheme 33). 

Some interesting fused 1,2,3-triazole ring systems have been reported. A series of 5-piperidyl-substituted 7-hydroxy-3f/-l,2,3-triazolo[4,5-d]pyrimidines 143 has been synthesized from pipecolinate esters, benzylazides, and cyanoacetamide <06CHE246>. 4-Alkylidene-5,6-dihydro-4//-pyrrolo-[l,2-c][l,2,3]triazoles 144 were prepared from alkylidenecyclopropanes via diiodogenation/Cu(I)-catalyzed 1,3-dipolar cycloaddition/intra-molecular Heck reaction sequence <06SL1446>. 6,6-Dimethyl-2-phenyl-4,5,6,7-tetrahydro-27/-benzotriazol-4-one 145 were prepared from A-(5,5-dimethyl-3-oxocyclohexenyl)-S,S-diphenylsulfilimine and... 

In a similar tandem reaction, ethyl 2-azido-l-methyl-l/7-indole3-carboxylate 364 is converted to indolo[3,2- ]l,2,3-triazolo[l,5- ]pyrimidin-5-ones 366 via triazole intermediates 365 that are not separated (Scheme 58). Products 366 are obtained in 80-90% yield as potential intercalates of DNA <2003H(60)2669>. 

In boiling acetic acid for 3 hr, 3-aminotriazole and diethyl 1-ethoxyethylidenemalonate gave 1,2,4-triazolo[ 1,5- ]pyrimidin-5-one (1122, R = H, R1 = Me) in 39% yield. When this reaction was carried out in boiling... 

The reactions of 5-methylthio-3-amino- or 3,5-diamino-l,2,4-triazole and diethyl 1-ethoxyethylidenemalonate in boiling ethanol in the presence of sodium ethylate for 1.5-3.5 hr gave l,2,4-triazolo[l,5-a]pyrimidin-7-ones (1123, R = MeS, NH2, R1 = Me) in 44% and 20% yields, respectively. The reaction of 5-methylthio-3-amino-l, 2,4-triazole (R = MeS) and 2-ethoxyethylidenemalonate in boiling pyridine for 4 hr gave 1,2,4-tria-zolo[l,5-a]pyrimidin-5-one (1122, R = MeS, R1 = Me) in 12% yield (61JCS3046). 

Spickett and Wright investigated the reactions of 4-substituted 3-amino-1,2,4-triazoles and EMME in acetic acid for 24-48 hr [67JCS(C)503]. Generally, they obtained [l,2,4]triazolo[l,5-a]pyrimidine-7-ones (1124) in 38-56% yields. In the case of the benzyl derivative (R = CH2Ph), the isomeric triazolo[l, 5-a]pyrimidin-5-one (1125) was also isolated from the mother liquor, in 5% yield. From the 4-ethyl and 4-phenethyl derivatives (R = Et, CH2CH2Ph), l-(l,2,4-triazol-3-yl)pyridin-2-ones (1126) were also obtained in 1-2% yields. 

In the reaction of 4-benzyl-3-amino-1,2,4-triazole and 1-ethoxyethyli-denemalonate under the previous circumstances, 7-methyl-l,2,4-triazolo[l, 5-a]pyrimidin-7-one (1127) was prepared in 10% yield [67JCS(C)503]. 

Ethyl 5-aminopyrazole -carboxylates are converted into pyrazolo[3,4- / pyrimidines via condensation with Ph3P/Bt2 subsequent reaction with an arylazocyanate and further reacting two carbodiimide with amines. Yields ranged from 13 to 65% dependant on the substituent <2006MI1584, 2007BMCL2203>. A similar approach was used for synthesis of triazolo[4,5- / pyrimidine-7(6)ones from ethyl 4-aminothiazolo-5-carboxylates <2007MIxx>. 

A number of 3-(alditol-l-yl)-5-methyl-7-oxo-l,2,4-triazolo[4,3-a]pyrim-idines l,2,4-triazolo[4,3-a]pyrimidines acyclo C-nucleosides (30) were synthesized (95PHA784) by oxidative cyclization of the corresponding aldehydo-sugar pyrimidin-2-ylhydrazones 27 with bromine in water. The alternative structure 29 was eliminated based on finding that acetylation of 30 afforded the same acetylated acyclo C-nucleosides 31 as those obtained by oxidative cyclization of the (A3-acetyl-poly-0-acetyl)hydrazones 28. Compounds 31 were also obtained by one-pot oxidative cyclization and acetylation of 27. In contrast to the oxidation and concurrent bromination of 19 to 25, it was possible to avoid nuclear bromination of 27 and 28 by performing the reaction in the absence of light (Scheme 13). 

Similarly, cyclization of 3-amino-l, 2,4-triazoles (65) with methyl propio-late or methyl phenylpropiolate gave a mixture of the l,2,4-triazolo[4,3-a]pyrimidin-7-ones 97 and the l,2,4-triazolo[l,5-a]pyrimidin-7-ones 98 (70CB3266 71CB2702). In addition, methyl tram-3-(3-amino-l,2,4-triazol-l-yl)acrylates (99) were also obtained. Production of the 1,2,4-triazolopy-rimidines 97 and 98 started by condensation of the ester function with the amino group of 65, followed by cycloaddition of the triazole N4 or N1 of the two tautomeric intermediates 96a and 96b, respectively, onto the carbon-carbon triple bond of the side chain. In contrast, formation of the triazolyl acrylates 99 took place through addition only of the triazole N1 onto the propiolate carbon-carbon triple bond. The relative amounts of products were found to depend on the reaction conditions (temperature, solvent, and time) (70CB3266) (Scheme 42). 

Related to Scheme 42 was the reaction of 65 with dimethyl acetylene-dicarboxylate, which gave a mixture of 7-methyoxycarbonyl-l, 2,4-tria-zolo[4,3-o]pyrimidin-5-one (101), 7-methoxycarbonyl-l,2,4-triazolo[l,5-a]pyrimidin-5-one (102), and dimethyl (3-amino-l,2,4-triazol-l-yl)fumarate (103) (71CB2702) (Scheme 43). 

Reaction of 5,7-dimethyl-l,2,4-triazolo[l,5-a]pyrimidine (246) with phenacyl bromide gave the triazolopyrimidinium salt 247 (85JCS(P1)2333 85TL1321). Treating 247 with one equivalent of triethylamine gave the ylide 248, whose thermolysis in acetonitrile gave Af-cyano-lV-phenacylaminopy-rimidine (249), but when 247 was treated with two equivalents of triethylamine, the 2-iminooxazoline 250 was formed, which was also obtained from 249 by further treatment with another equivalent of triethylamine (Scheme 46). 

Condensation of 2-hydrazinopyrimidine (384) with an aromatic aldehyde formed the Schiff bases (386), which then cyclized with bromine to 6-bromo-l,2,4-triazolo[4,3-a]pyrimidine (383) and with carbon disulfide to 387 (92PS145). A similar cyclization was effected also on 384 to give 388 (68T2839 85FRP2549834), but the cyclization of 384 or 385 with carbon disulfide afforded 3-thiolo-l,2,4-triazolo[4,3-a]pyrimidin-7-ones 389 and 390, respectively. A small amount of the isomeric 3-thiolo-l, 2,4-triazolo[4,3-a]pyrimidin-5-one was isolated in the former case (68T2839). Reaction of 385 with benzaldehyde [67JCS(C)498] or p-chlorobenzaldehyde (90MI3) followed by oxidation with LTA in benzene afforded 391 (Scheme 73). 

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,... 

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