Synthesis of some new annelated fused pyrimidine derivatives and study of their biological activities

Abstract

The synthesis ofthe fused pyrimidine is divided into two headings: such as; annelated substrate and annelating reagent. The annelating substrate artha-amino ester as ethyl- 5-amino-l-methylpyrazol-4-carboxylate (2), which was prepared from 8 14).R=-@ IS). R = - Si(Cl-j)3 16). R = - Cli - OH 17). R~ - (CIi)3 - CH:J COOEt N~C=C-R I Me 4 ethyl(ethoxymethylene)cyanoacetate by usmg Gewald procedure and annelating reagents as 2-methylthio-2-methylthiazoline (7) and 2-methylthio-imidazoline (11), which were synthesized from ethanol amine (5) and diethylamine (9) by using Jensen & Hofmann method. The annelating substrate (2) was used in the synthesis of 1- methyl-4-oxo-5-(p-toluoyl)-pyrazolo[3,4-djpyrimidin (4). The annelating substrate (2) was used to synthesize l-rriethyl-6,7-dihydropyrazolo[3,4-djthiazolo[I,2- ajpyrimidine-4-one (8) and l-methyl-6,7-dihydropyrazolo[3,4-djimidazo(l,2- ajpyrimidin-4(8H)-one (12) by one step reaction in dry acetic acid. The compounds ethyl-5-iodo-l-methylpyrazol-4-carboxylate (13), ethyl-5-phenylethynyl-lmethylpyrazol- 4-carboxy late (14), ethy1-5-trimethylsilylethynyl-l-methylpyrazol-4- carboxylate (15), ethyl-5-propynylol-l-methylpyrazol-4-carboxylate (16) and ethyl-5- hexayne-l-methylpyrazol-4-carboxylate (17) were synthesized from annelating substrate (2). In vitro antimicrobial activity of fused primidine and 5-alkynyl pyrazol derivatives were evaluated. All the synthesized compounds demonstrated mild growth inhibition against antibiotic-susceptible standard and clinically isolated strains of gram-positive and gram-negative bacteria as well as human fungal pathogens.