Design and synthesis of some tricyclic pyrimidines and triazines via cycloaddition and intermolecular cyclization of cyclic amidine

• Published in: Journal of the Iranian Chemical Society 2017-10, Vol.14 (10), p.2239-2246
• Main Author: El-Sayed, Hassan A.
• Format: Article
• Language: English
• Subjects: Acetylacetone; Analytical Chemistry; Benzamide; Benzoylation; Biochemistry; Chemical reactions; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chlorination; Chloroformate; Cycloaddition; Derivatives; Inorganic Chemistry; Organic Chemistry; Original Paper; Physical Chemistry; Pyrimidines
• ISSN: 1735-207X; 1735-2428
• DOI: 10.1007/s13738-017-1160-7

The cyclic amidine 3 was used as a precursor in this research, which was synthesized by chlorination of compound 1 , followed by ring closure with hydrazine hydrate. Cyclization of amidine compound 3 with acetylacetone, ethyl cyanoacetate, chalcone analogue 6 and benzylidenemalononitrile ( 8 ) tolerated the expected tricyclic pyrimidines 4 , 5 , 7 and 9, respectively. Reaction of 3 with ammonium thiocyanate followed by cyclization of the product 10 with DMF, ethyl chloroformate and chloroacetyl chloride afforded triazine derivatives 11 – 13 , respectively. Nucleophilic substitution of the later compound with EtONa gave ethyl methyl ether derivative 14 . The benzamide derivative 15 was obtained by reaction of 3 with benzoylisothiocyanate or benzoylation of compound 10 with benzoyl chloride. Finely, heterocylization of 15 in the presence of Et 3 N gave the triazine derivative 16 . Graphical abstract 6-(4-Chlorophenyl)-4-(4-isopropylphenyl)-1 H -pyrazolo[3,4- b ]pyridin-3-amine ( 3 ) was used as the starting material for the synthesis of pyrido[2′,3′:3,4]pyrazolo[1,5- a ]pyrimidine and pyrido[2′,3′:3,4]pyrazolo[1,5- a ][1,3,5]triazine derivatives via cycloaddition and intermolecular cyclization reactions.