Triazolo pyrimidines, formation

Reaetion of l,3-benzoxazin-4-ones (43, 44) or trithioisatoie anhydride (45) with amidrazones (46, 47) or thiosemiearbazide (48) resulted in the formation of 3-(l-amidino)- (49-51) and 3-(l-thioureido)pyrimidines (52) respeetively. Compounds 49-52 underwent thermal intramoleeular ey-elization to the eorresponding l,2,4-triazolo[l,5-c]quinazolines (53-56) [68CB2106 76MI1 80PHA582 83MI1 85H(23)2357] (Seheme 18). 

Four general methods were used to aehieve simultaneous formation of both of the triazole and pyrimidie rings of l,2,4-triazolo[l,5-c]pyrimidines ... 

Heating the 5-isocyano-l,3,4-thiadiazolo[3,2- ]pyrimidin-5-one 115 with 10% hydrochloric acid gave a mixture of the 5-imino-l,3,4-thiadiazolo[3,2- ]pyrimidin-7-one 116 (10%) and the l,2,4-triazolo[l,5-c]pyrimidine-5,7-dione 117 (35%) (91JHC489). Formation of 117 probably occurred through thiadiazole ring rupture of 116 and recyclizatioii with its imino function together with desulfurization (Scheme 43). 

Heating the mesoionic l-amino-2-thioxo-l,2,4-triazolo[l,5-c]quinazo-lines 59 with aromatic aldehydes and ethanolic hydrochloric acid resulted in the formation of Schiff bases and simultaneous pyrimidine ring cleavage... 

Studies by Almerico and co-workers into the synthesis of annelated l,2,3-triazolo[l,5- ]pyrimidines have led to an efficient method for the formation of the five- and six-membered rings onto a substituted pyrrole in good yield <2002T9723>. The reaction proceeds initially via a 1,3-dipolar cycloaddition between the azide group of 300 and the... 

Two types of addition to pyrimidine bases appear to exist. The first, the formation of pyrimidine photohydrates, has been the subject of a detailed review.251 Results suggest that two reactive species may be involved in the photohydration of 1,3-dimethyluracil.252 A recent example of this type of addition is to be found in 6-azacytosine (308) which forms a photohydration product (309) analogous to that found in cytosine.253 The second type of addition proceeds via radical intermediates and is illustrated by the addition of propan-2-ol to the trimethylcytosine 310 to give the alcohol 311 and the dihydro derivative 312.254 The same adduct is formed by a di-tert-butyl peroxide-initiated free radical reaction. Numerous other photoreactions involving the formation by hydrogen abstraction of hydroxyalkyl radicals and their subsequent addition to heterocycles have been reported. Systems studied include 3-aminopyrido[4,3-c]us-triazine,255 02,2 -anhydrouri-dine,256 and sym-triazolo[4,3-fe]pyridazine.257 The photoaddition of alcohols to purines is also a well-documented transformation. The stereospecific addition of methanol to the purine 313, for example, is an important step in the synthesis of coformycin.258 These reactions are frequently more... 

Ethyl 3-azido-l-methyl-177-indole-2-carboxylate 361 is prepared in 70% yield by diazotization of amine 360 followed by substitution of the created diazonium group with sodium azide. In cycloadditions with nitrile anions, azide 361 forms triazole intermediates 362. However, under the reaction conditions, cyclocondensation of the amino and ethoxycarbonyl groups in 362 results in formation of an additional ring. This domino process provides efficiently 4/7-indolo[2,3-i ]l,2,3-triazolo[l,5- ]pyrimidines 363 in 70-80% yield (Scheme 57) <2006TL2187>. 

A nucleophilic attack of morpholine on the pyrimidine ring in l,2,3-triazolo[l,5- ]pyrimidinium salts 1203 leads to unstable intermediates 1204. Spontaneous opening of the pyrimidine ring results in formation of 1,2,3-triazole derivatives 1205 that are isolated in 80-85% yield. A similar nucleophilic attack of the hydroxide anion (from aq. K2CO3) on dimethoxy derivative 1203 provides transition species 1206 that opens to intermediate 1207, and finally tautomerizes to ester 1208, isolated in 87% yield (Scheme 200) <2003T4297>. 

A rapid synthesis of trisubstituted l,2,4-triazolo[4,3-b]pyridazines has been devised to give selective variation of the three substituents through combinations of silicon-directed anion formation, palladium-catalyzed couplings and SnAt displacements <00TL781>. The synthesis of new l,2,4-triazolo[l,5-a]pyrimidines <00M1435>, 1,2,3-triazolo[4,5-(f]... 

The formation of l,2,4-triazolo[l,5- ]pyrimidines (TP) (la) was first reported by Biilow and Haas (09CB4638). Over the next 50 years, only a... 

These reactions are summarized in Table V and collected according to the Crsynthons used and the substituents R1 entering the newly formed triazole ring. Superscripts to references indicate formation of 1,2,4-triazolo[4,3-a] (a) and -[l,5-a]pyrimidines (b) a description of the re-... 

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). 

Thermally induced isomerization of 33 was suggested to take place through the formation of the acyclic intermediate 128 [66JCS(C)2031]. Recyclization of the latter gives the isomeric l,2,4-triazolo[l,5-a]pyrimidines 121 (Scheme 53). 

Hydrazinolysis of l,2,4-triazolo[4,3-a]pyrimidines (33) caused pyrimidine ring cleavage and led to the formation of the pyrazole 143 and 3-amino-1,2,4-triazole derivatives 65 (58YZ1395 62ZC369 76KGS706). A probable mechanism of this reaction is shown in Scheme 56. 

Cyclization of the diamidine 154 with acetyl- or benzoyl-acetone (153) gave l,2,4-triazolo[l,5-a]pyrimidine (156) via the formation of 155 (66CB2237 79AP1003). Alternatively, 156 can be prepared by the reaction of 153 with the diaminotriazole 157 (66CB2237) (Scheme 29). 

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,... 

Refluxing of dihydroazoloazines and a,(3-unsaturated ketones in a methanol solution of sodium methoxide proceeds in a Michael-type addition. For example, reaction of 2-methyl-5,7-diaryl-6,7-dihydropyrazolo[l,5- ]pyrimidine 387 and chalcone 5 under these conditions yields adduct 388 [297] (Scheme 3.102). Treatment of 2-methyl-substututed triazolopyrimidine 389 with ketone 5 leads to cyclization with formation of the triazolo[5,l-Z ]quinazoline moiety [324]. 

Radiolabelled derivatives of the herbicide florasulam (N-(2,6-difluo-rophenyl)-5-methoxy-8-fluoro(l,2,4)-triazolo-[l,5-c]-pyrimidine-2-sulphon-amide) (VII) were exposed to natural sunlight in a sterile pH 5 buffer water and in a natural lake water collected from 20 to 30 cm below the surface [70]. The photo degradation was much faster in the natural water system, with a half-life of 3.3 days against 73 days in the buffered aqueous medium. Moreover, the photoproducts produced in the distilled and natural waters were found to be different. Direct photolysis led to the cleavage of the N - S bond with formation of the sulphonic acid derivative (Vila) after 10% of conversion (see Scheme 7). 

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