Synthesis and antimalarial effects of 2‐(3,4‐dichloroanilino)‐7‐[[[(dialkylamino)alkyl]amino]]‐5‐methyl‐s‐triazolo[1,5‐a]pyrimidines

Abstract 3,4‐Dichlorophenylisothioeyanate (10) was allowed to react with 2‐methy1‐2‐thiopseudourea to give methyl 4‐(3,4‐dichlorophenyl)(dithioaltophanimidate (11) (41%), which upon treatment with hydrazine afforded 3‐amino‐5‐(3,4‐dichloroanilino)‐s‐triazole (12) (54‐91%). Ring‐closure with ethyl acetoacetale in acetic acid afforded 2‐(3,4‐dichloroanilino)‐5‐methyl‐s‐triazolo[ 1,5‐α ]‐pyrimidin‐7‐ol (13) (81%). Chlorination with phosphorus oxychloride gave 7‐chloro‐2‐(3,4‐dichloroanilino)‐5‐methyl‐s‐triazolo[1,5‐α ]pyrimidine (14) (98%), which was condensed with various amines to yield the desired 2‐(3,4‐diehloroanilino)‐7‐¶[(dialkylamino)alkyl]arnino¶‐5‐methyl‐s‐triazolo[ 1,5‐α]pyrimidines (6a‐d). The structures of the s‐triazolo[ 1,5‐α ]pyrimidines were based on nmr spectroscopy and ring stability considerations. Several of the amino‐s‐triazolo[ 1,5‐α ]pyrimidines possessed antimalarial activity against P. berghei in mice.