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Synthesis and antimalarial effects of 2‐(3,4‐dichloroanilino)‐7‐[[[(dialkylamino)alkyl]amino]]‐5‐methyl‐ s ‐triazolo[1,5‐ a ]pyrimidines
Author(s) -
Werbel Leslie M.,
Elslager Edward F.,
Chu Vera P.
Publication year - 1973
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570100435
Subject(s) - chemistry , ring (chemistry) , pyrimidine , hydrazine (antidepressant) , yield (engineering) , alkyl , acetic acid , nuclear magnetic resonance spectroscopy , 1,2,4 triazole , bicyclic molecule , medicinal chemistry , stereochemistry , organic chemistry , materials science , chromatography , metallurgy
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 ( 6 a‐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.