5.7- Dichloro-1,2,4-triazolo pyrimidine

The 5- and 7-positions of the l,2,4-triazolo[l,5-a]pyrimidine ring are very reactive toward nucleophilic substitution, the 7-position being the more reactive. Thus, the 7-substituted and 5,7-disubstituted triazolo[l,5-a]pyrim-idines 185 and 186 were prepared by the reaction of 5,7-dichloro-l,2,4-triazolo[l,5-a]pyrimidine (184) with amines or hydrazines [81KFZ31 88IJC(B)825 91PHA184] (Scheme 35). 

Reaction of the 3-substituted l,2,3-triazolo[4,5-d]pyrimidines (183) with one equivalent of a Grignard reagent in THF afforded the dihydro compounds 185 after hydrolysis of the intermediates 184. Aromatization of 185 by oxidation with potassium ferricyanide (79CPB3176) or with 2,3-dichloro-4,5-dicyanobenzoquinone (DDQ) (89CPB1731) gave the 3-substituted 7-alkyltriazolopyrimidines 186. Replacement of the methylsul-... 

Replacement of the two chlorine atoms in 3-phenyl-5,7-dichloro-l,2,3-triazolo[4,5-d]pyrimidine gave 3,5,7-trisubstituted triazolopyrimidine derivatives [84JAP(K)5962595], which showed anticarcinogenic activity against sarcoma tumor cells in mice. Compounds 159 have been used as an-ticarcinogenics [81JAP(K)8131586,81JAP(K)8131587]. 

Cyclization of the 2,2-dichloromalonic acid dipyrrolidine diimidoyl dichloride 64 with hydrazine hydrate caused concurrent double ring closure to afford the 8,8-dichloro-3,5-dipyrrolidino-l,2,4-triazolo[4,3-c]pyrimidin-7(8//)-one 66 as explained in scheme 28 (86CB129). 

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