2-Aminothiophen-3-carboxamide as Starting Materials in Synthesis of Thieno[2,3-d]pyrimidine derivatives

Variety of substituted 2-aminothiophenes has been developed by Gewald and co-workers[1]. Application of 2-cyanoacetamide in Gewald reaction leads to formation of 2-aminothiophene-3- carboxamides (Gewald‘s amide) which are 1,5-dinucleophiles applied for synthesis of diverse thieno[2,3-d]pyrimidine derivatives. Previously, pharmacological studies of the thienopyrimidine derivatives extensively showed variety of activities such as antibacterial, antimicrobial, anxiolytic, and psychotropic[2]. The synthesis of the target compounds 2-amino-thiophene-3-carboxamides were prepared from cyclic ketones and sulfur with either ethyl cyanoacetate or cyanoacetamide, in the presence of morpholine via the Gewald thiophene synthesis. Treatment 2-aminothiophene-3- carboxamides with aromatic aldehydes and molecular iodine gave products 4[3].