Direct Synthesis of Multi‐functional Pyrimidine, Pyrazine, and Pyridine Scaffolds via Inter‐ and Intramolecular Annulations of 3‐Amino‐thieno[2,3‐b]pyridine‐2‐carboxylate

Abstract

The synthesis of a new series of annulated thieno[2,3‐b]pyridines was performed. Ester compound 1 underwent heterocyclization upon reaction with phenylisothiocyanate and formamide to afford pyrimidines 2 and 3, respectively. Thienopyrimidine 5 was resulted via reaction of amino derivative 1 with triethyl orthoformate to afford the non‐isolable intermediate 4, which allowed hydrazinolysis with hydrazine hydrate to afford the target compound. Pyrimidine type 5 was condensed with p‐nitrobenzaldehyde to afford Schiff base 6. Refluxing of ester 1 with ethyl cyanoacetate and diethyl malonate followed by base‐mediated heterocyclization afforded condensed pyridines 8 and 9, respectively. The tetracyclic pyrazine derivative 14 was obtained from the reaction of amino compound 1 with 2,5‐dimethoxytetrahydrofuran followed by hydrazinolysis to give carbohydrazide 11, which undergo diazotization followed by Curtius rearrangement. The antibacterial results illustrated no significant results for the investigated compounds except compound 5, which has moderate activity against Gram‐positive bacteria.

Heteroannulation of 2‐amino‐6‐thioxouracil: A new access for the synthesis of fused pyrimidine derivatives

“…Moreover, its 13 As depicted in Scheme 5, pyruvic acid derivative 2 undergoes heterocyclization with pyrimidine derivative 10a in the presence of sodium acetate to provide 3-benzyl-7-hydroxy-5-(4-hydroxyphenyl)-2-(phenylamino) pyrido[2,3-d]pyrimidin-4(3H)-one (17) in good yield (75%) (Scheme 5). Compound 12a yielded signals at δ 8.97, 9.77, 11.73, and 11.77 ppm (D 2 O exchange) for NH and OH protons, respectively, in addition to the methylenic and aromatic protons splitted at δ 4.89 and 7.22 to 8.92 ppm, respectively.…”

“…6-Amino-2-(arylamino)-3-benzylpyrimidin-4(3H)-ones (10a,b) contain enamine system at C-5 and C-6 that enable it to act as building blocks for constitution of a variety of bi-, tri-, and tetracyclic nitrogen containing heterocyclic scaffolds. Thus, keeping the compounds As depicted in Scheme 5, pyruvic acid derivative 2 undergoes heterocyclization with pyrimidine derivative 10a in the presence of sodium acetate to provide 3-benzyl-7-hydroxy-5-(4-hydroxyphenyl)-2-(phenylamino) pyrido[2,3-d]pyrimidin-4(3H)-one (17) in good yield (75%) (Scheme 5). The reaction proceeds via Michael addition followed by intramolecular cyclization, decarboxylation, and aromatization.…”

“…Additionally, pyrimidines and their fused systems act as the main constituent in many applicable molecules such as herbicides, plant growth regulators, [11,12] pesticides, [13] and fluorescent brighteners. [16][17][18] In the present context, we describe a facile and direct protocol for the construction of a new series of thiopyrano-, thieno, pyrrolo-, and pyridopyrimidine via heteroannulation of 2-amino-6-mercaptouracil (1). [15] Our interests directed to develop a new and efficient synthetic approach for several types of heterocyclic systems using simple reagents with convenient biological properties.…”

“…[15] Our interests directed to develop a new and efficient synthetic approach for several types of heterocyclic systems using simple reagents with convenient biological properties. [16][17][18] In the present context, we describe a facile and direct protocol for the construction of a new series of thiopyrano-, thieno, pyrrolo-, and pyridopyrimidine via heteroannulation of 2-amino-6-mercaptouracil (1).…”

An efficient synthesis of 4,6‐diarylnicotinonitrile‐acetamide hybrids via 1,2,3‐triazole linker as multitarget microbial inhibitors

“…The second reason is the use of azide‐alkyne cycloaddition methodology in the synthesis of such moiety. Recently, our approaches are directed to development of new hybrid nicotinonitrile scaffolds with pharmacophore and fluorophore properties [18,23–27]. The current work describes an efficient synthetic click coupling between acetylenic nicotinonitrile and azidoacetamide aimed to form bacterially active hybrid molecules via 1,2,3‐triazole linker.…”