ORIGINAL PAPER Heterocyclization of ethyl 3-amino-4,6-dimethylthieno [2,3-b]pyridine-2-carboxylate (review) Hassan A. El-Sayed Received: 9 March 2013 / Accepted: 27 May 2013 Ó Iranian Chemical Society 2013 Abstract This review describes the synthesis and reactions of ethyl 3-amino-4,6-dimethylthieno[2,3-b]pyridine-2-car- boxylate as building block for the synthesis of polyfunc- tionalized heterocyclic compounds with pharmaceutical interest. Keywords Thieno[2,3-b]pyridine Á o-Aminoester Á Heterocyclization Á Pyridine carboxylate Á Potassium salt Introduction When thiophen and pyridine ring systems are fused toge- ther various condensed ring systems may arise from such fusion. Ethyl 3-amino-4,6-dimethylthieno[2,3-b]pyridine- 2-carboxylate has been used as versatile precursor to pre- pare several heterocyclic compounds. The o-aminoester moiety of the molecule is a favorable unit to react with both electrophiles and nucleophiles usually result in the formation of heterocyclic systems. Furthermore, ethyl 3-amino-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate 3 has been used to synthesize several azodyes [1], and several biological active compounds [2]. Synthesis When the reaction of 4,6-dimethyl-2-thioxo-1,2-dihy- dropyridine-3-carbonitrile (1) with ethyl chloroacetate was carried out in a high boiling point solvent such as pyridine [3] or in the presence of a relatively strong base such as potassium carbonate [4–6], potassium hydroxide [7, 8], or sodium alkoxide [9–11], the corresponding ethyl 3-amino- 4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate (3)[4, 6, 11] were directly obtained (Scheme 1). On the other hand, the reaction of pyridinethione 1 with ethyl chloroacetate in the presence of sodium ethoxide [12] yielded c (2), which underwent Thrope–Ziegler cyclization in 10 % ethanolic KOH to afford 3 ethyl 3-amino-4,6-dimethylthieno[2,3- b]pyridine-2-carboxylate (3) (Scheme 1)[13]. Reactivity Ethyl 3-amino-4,6-dimethylthieno[2,3-b]pyridine-2-car- boxylate is polyfunctional compound possing both nucle- ophilic and electrophilic properties (Fig. 1). Typical nucleophilic position is NH 2 group, while the electrophilic position is the ester carbonyl, additionally two centers present in 1,2-positions. These different chemical proper- ties have been used to design different heterocyclic moie- ties such as azoles, azines and azepine derivatives. Reactions Diazotization Diazotization of compound 3 by adding sodium nitrite solution in water afforded the corresponding 3-diazo-2-eth- ylcarbonyl-4,6-dimethylthieno[2,3-b]pyridine (4), which on reaction with thiourea, guanidine carbonate, and hydroxylamine hydrochloride gave the corresponding 7,9-dimethyl-2-thioxo-1,3-dihydropyrido[5,4- b]thieno [3,2- d]pyrimidin-4-one (5), 2-amino-7,9-dimethylpyrido H. A. El-Sayed (&) Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt e-mail: hasanneg@gmail.com 123 J IRAN CHEM SOC DOI 10.1007/s13738-013-0283-8