Combinatorial Synthesis of Fused Tetracyclic Heterocycles Containing [1,6]Naphthyridine Derivatives under Catalyst Free Conditions

Abstract

A three-component reaction between an aromatic aldehyde, an amine, and tert-butyl 2,4-dioxopiperidine-1-carboxylate in EtOH at refluxing temperature gave fused tetracyclic heterocycles in high yields. The amines include 1H-indazol-5-amine, 1H-indazol-6-amine, 1H-indol-5-amine, and 1H-benzo[d]imidazol-5-amine, giving 11-aryl-3H-indazolo[5,4-b][1,6] naphthyridine, 11-aryl-1H-indazolo[6,7-b][1,6]naphthyridine, 11-aryl-3H-indolo[5,4-b][1,6]naph-thyridine, and 11-aryl-3H-imidazo[4',5':3,4]benzo[1,2-b][1,6]naphthyridine derivatives, respectively.

Domino synthesis of functionalized 1,6-naphthyridines and their in vitro anti-inflammatory and anti-oxidant efficacies

“…2,3 These pyridine structures are the most significant because of their wide spectrum of promising biological activities such as anticonvulsants, 4 anti-inflammatory, 5 antimitotic, 6 agents antioxidant, 7,8 anticancer, 9,10 and antimicrobial activities. 11 Similarly, 1,6-naphthyridines [12][13][14][15][16][17] have established significant attention due to their broad range of bioactivities [18][19][20][21][22][23][24] such as antimicrobial, 25 anti-analgesic, 26 antifungal, 27,28 anticancer, [29][30][31] antioxidant, 31 anti-inflammatory, [27][28][29]32 antiarrhythmic, 33 antitumor 34 , anti HSV-1 35 anti-HIV 36,37 activities and act as inhibitors of acetylcholinesteras. 38 Structures of few previously reported biologically active 1,6-naphyridines (A-G) are shown in Figure 1.…”

One‐Pot Multicomponent Reaction: A Highly Versatile Strategy for the Construction of Valuable Nitrogen‐Containing Heterocycles

“…Unlike the previous reports, Wang and co‐workers developed a facile approach for the construction of fused tetracyclic heterocycles having core naphthyridine moiety using aromatic aldehyde, amine, and tert ‐butyl 2,4‐dioxopiperidine‐1‐carboxylate in EtOH under refluxing condition (Scheme 6). [40] A library of naphthyridine derivatives was synthesized using various aromatic aldehydes containing both electron‐withdrawing and electron‐donating groups with good to excellent yield of the corresponding products. Further, amines such as 1 H ‐benzo[ d ]imidazol‐5‐amine 27 , 1 H ‐indol‐5‐amine 28 , 1 H ‐indazol‐6‐amine 29 , and 1 H ‐indazol‐5‐amine 30 , produced the corresponding fused tetracyclic1,6‐naphthyridine derivatives demonstrating the versatile nature of this reaction protocol.…”

An Exceedingly Mild, Green Synthesis of Substituted N‐3‐diaryl‐1,8‐naphthyridin‐2‐amine Derivatives and Their Antimicrobial Activity

“…In recent years, research on derivatives of 1,8‐naphthyridines represents an significant class of organic molecules that attract the interest of medicinal chemists because of their extremely wide spectrum of bio‐organic/chemical/medicinal/pharmaceutical and biological importance as well as their use as important binding units in the molecular plan of synthetic receptors . 1,8‐naphthyridine derivatives attract the interest of much biological importance, such as anti‐tumor , anti‐mycobacterial , anti‐allergic , antibacterial , anti‐inflammatory , anti‐hypertensive , anti‐HIV and local anesthetic .…”