Yb(OTf)3 catalyzed new cascade reaction: a facile assembly of fused quinazolinones

Abstract

A one-pot Yb(III)-mediated cascade reaction has been developed leading to small molecules based on a novel structural motif, i.e. quinazolin-4-one moiety fused with an isoquinoline ring, for potential inhibition of TNF-α.

Diversity‐Oriented Synthesis of Polycyclic Indoles: Brønsted or Lewis Acid Catalyzed Three‐Component Reaction for the Synthesis of α‐Carbolines and Pyrimidoindoles

“…1 H,13 C, HRMS matches well with the data reported above.2-(4-Chlorophenyl)-4-phenyl-9H-pyrido[2,3-b]indole (5acb):Yield 207 mg (48 %); white solid; R f = 0.42 (ethyl acetate/hexane, 10 %); m.p. 240-242°C.…”

“…This prompted us to explore the abilities of various Lewis acid driven transformations because their application in the synthesis of structurally diverse heterocycles has been well documented. Increasing the concentration of TFA from 10 to 100 mol-% resulted in a gradual decrease in the isolated yields of 4aaa from 40 to 23 % and simultaneous enhancement in the isolated yield of 5aaa from 38 to 53 % (entries [13][14][15]. Switching solvent from toluene to N,N-dimethylformamide (DMF) or dimethyl sulfoxide (DMSO) failed to produce the final products (entries 6 and 7).…”

“…Our findings thus suggest that by manipulating the reaction conditions it may be possible to obtain two distinct annulated products. Following activation of the alkyne moiety by Yb, [13] III may then undergo concomitant intramolecular nucleophilic attack from the indolic N a -H to afford dihydro intermediate IV. Attempts to replace Yb(OTf) 3 with Sc(OTf) 3 and Zn(OTf) 3 furnished 4aaa in diminished yield (Table 1, entries 10 and 11), whereas addition of p-toluenesulfonic acid (pTsOH) as a catalyst afforded 4aaa in poor yield (entry 12).…”

“…1 H NMR (400 MHz, CDCl 3 ): δ = 8.36 (s, 1 H), 8.23-8.21 (m, 2 H), 7.72-7.64 (m, 5 H), 7.60-7.58 (m, 2 H), 7.09 (s, 1 H), 6.84-6.81 (m, 1 H), 6.46 (d, J = 8.0 Hz, 1 H), 4.60 (q, J = 8.0 Hz, 2 H), 2.51 (s, 3 H), 1.61 (t, J = 7.2 Hz, 3 H) ppm 13. 200-202°C; R f = 0.52 (ethyl acetate/hexane, 10 %).…”

Synthesis and biological evaluation of pyridazino[1′,6′:1,2]pyrido[3,4-b]indolinium and pyridazino[1,6-a]benzimidazolium salts as anti-inflammatory agents

“…To date, very few molecule-based inhibitors have been reported for the inhibition of in vitro TNF receptor 1 (TNFR1) binding to TNF-a, which is an interesting new approach that involves proteineprotein binding inhibition [12,13]. Some inhibitors bearing quinazolinone [14,15], quinuclidine, or quinolizine [16] frameworks proved to bind TNF-a in silico. The strongest small-molecule TNF-a inhibitor reported to date, SPD304, promotes subunit disassembly of this trimeric cytokine [17] (Fig.…”