Thiadiazolo pyrimidines

5- Thiadiazolo [3,4 ]pyrimidines.—7-Amino-l, 2,5-thiadiazolo[3,4- /]pyrimidine (197) 169 displays numerous analogies in its properties with the comparable 4-aminopteridine, including its enzymatic oxidation by xanthine oxidase to the corresponding 5-hydroxy-compound. ° 

5- Thiadiazolo[3,4-6]pyrazines.—A number of members of this ring system have been prepared by the interaction of 2,3-diamino-p3rrazines with thionyl chloride, and their properties studied.  

Condensation of 3,4-dimethoxy-l,2,5-thiadiazole 1,1-dioxide with ethylene-diamine gives 4,5,6,7-tetrahydro-l,2,5-thiadiazolo[3,4-6]pyrazine 2,2-dioxide (198) in excellent yield.  

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Reid et al. have reported that the reaction of thiadiazolo pyrimidine derivatives with isocyanates, isothiocyanates, and isoselenacyanates, with elimination of acetonitrile and concomitant addition of two molecules of the hetero-cumu-lene, gave the corresponding 7r-sulfuranes 86-93, as shown in Fig. 10 [84]. The molecular structures of 87 (R=Et, Ph) were determined by X-ray crystallographic analysis [85]. 

Treatment of 5,7-diamino-l,3,4-thiadiazolo[3,2-n]pyrimidinium ehloride (25) with Vilsmeier reagent gave the 7-formamido-l,2,4-triazolo[l,5-c]pyrimidin-5-one (27) (90JHC851) (Seheme 42). Compound 27 has presumably been formed via rupture of the 1,3,4-thiadiazole ring of 25 and... 

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). 

When 7r-deficient thiadiazoles are fused to an azine, electrophilic substitution is possible only in the presence of strongly electron-donating substituents (74BCJ2813) (Scheme 56). Some [l,3,4]thiadiazolo[3,2-a]pyrimidin-5-ones were brominated next to the oxo group (90DOK743). 

Iminothiodiazolopyrimidinones 55 and2,4-pentanediones condense inpolyphosphoric acid to yield 9-oxo-l,2,3,4-thiadiazolo[3,2-a]pyrido[3,2-e ]pyrimidines 56 <95IZV2037 96CA(124) 289413 >. 

Very many fused 1,2,5-thiadiazoles, and some fused 1,2,3-thiadiazoles, have been prepared the two typical reactions are illustrated (Scheme 8). The first is exemplified by the synthesis of numerous benzo- and hetero-fused 1,2,5-thiadiazoles by Carmack and co-workers,68 and by Hartman s group 69 an example of the second is the preparation of l,2,3-thiadiazolo[4,5-d]-pyrimidines.70... 

Similar treatment of 5-nitrobenzothiadiazole 97 with ethyl isocyanoacetate and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave the thiadiazolo[3,4-< ]isoindole 93 (21%), but when a phosphazene base was employed the major isolated product was the pyrimidine fV-oxide 98 (46%) (Equation 13) <1996J(P1)1403, 1996TL8391>. 

Transformations of various 2-bromo-substituted derivatives of [l,3,4]thiadiazolo[3,2-tf]pyrimidines are shown in Scheme 27. Thus, reaction of 218 with dimethylamine gave 219 in medium yield <2005JHC1105>, treatment of 220 with mercaptans afforded 221 in good yield <1999IZV1154>, whereas reaction of 222 with hetarylamines and hetarylmercaptanes yielded 223 <1993IZV1954, 1994KGS560>. 

Table 11 Novel transformations to [1,3,4]thiadiazolo[3,2-a]pyrimidine and its benzologues by using old methodologies...

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