ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

New synthetic approaches to thieno[3,2-d]pyrimidine and thieno[3,4-b]pyridine derivatives

Salwa E. M. El-Meligie, Nadia A. Khalil, Hala B. El-Nassan, and Ahmed A. M. Ibraheem

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt

E-mail: hala_bakr@hotmail.com

Received: 28 January 2020  Accepted: 1 February 2020

Abstract:

In this work, 3-amino-4-cyano-2-thiophenecarboxamides 1a-k were used as versatile synthons for the preparation of thieno[3,2-d]pyrimidine-7-carbonitriles 2a-k and 4a-d as well as the unexpectedly prepared thieno[3,4-b]pyridine-7-carboxamides 5a-e. Thus, heating thiophene-2-carboxamides 1a-k in formic acid afforded thieno[3,2-d]pyrimidin-4-ones 2a-k. Alternatively, the reaction of compounds 1a-i with 2,2,6-trimethyl-4H-1,3-dioxin-4-one (TMD) in xylene produced the β-keto amides 3a-i. The latter were cyclized to thienopyrimidine-2,4-diones 4a-d by heating with pyrrolidine in toluene using calcium chloride as a desiccant. While refluxing a mixture of β-keto amide derivatives 3a, 3d, 3e, 3f or 3 h and potassium carbonate in ethanol or in ethylene glycol afforded the thieno[3,4-b]pyridine derivatives 5a-e.

Keywords: 3-Amino-4-cyanothiophene; Thiophene-2-carboxamide; β-Keto amide; Thieno[3, 2-d]pyrimidine; Thieno[3, 4-b]pyridine

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-020-01089-2

Chemical Papers 74 (8) 2501–2514 (2020)