Synthesis of New 5-Aryl-benzo[f][1,7]naphthyridines via a Cascade Process (Ugi-3CR/Intramolecular Aza-Diels-Alder Cycloaddition)/Aromatization

Abstract

A series of eight new 5-aryl-benzo[f][1,7]naphthyridines were synthesized in 17 to 64% overall yields via an improved MW-assisted cascade-like one pot process (Ugi–three component reaction/intramolecular aza-Diels-Alder cycloaddition) coupled to an aromatization process from tri-functional dienophile-containing ester-anilines, substituted benzaldehydes and the chain-ring tautomerizable 2-isocyano-1-morpholino-3-phenylpropan-1-one as starting reagents, under mild conditions. The doubly activated dienophile and the aza-diene functionalities of the eight new Ugi-adducts were exploited to perform an in situ aza-Diels-Alder cycloaddition/aromatization (dehydration/oxidation) process, toward the complex polysubstituted 5-aryl-polyheterocycles, which could be taken as starting point for further SAR studies because the benzo[f][1,7]naphthyridine is the core of various bioactive products. It is relevant to emphasize that the synthesis or isolation of benzo[f][1,7]naphthyridines containing a substituted aromatic ring in the C-5 position, has not been published before.

Iron(III)-Catalysed Povarov Cyclisation for the Synthesis of Fused Dibenzo[b,f][1,7]naphthyridine Embedded Arylpyrrolo Scaffolds

“…1 H NMR (300 MHz, CDCl 3 ):  = 9.54 (s, 1 H), 7.47 (dt, J = 1.7, 0.8 Hz, 1 H), 7.32-7.28 (m, 1 H), 7.27-7.23 (m, 1 H), 7.20 (dt, J = 5.0, 1.7 Hz, 2 H), 7.16 (s, 1 H), 7.12-7.08 (m, 3 H), 6.46 (dd, J = 4.0, 2.5 Hz, 1 H), 2.45 (s, 3 H), 2.35 (s, 3 H). 13 C NMR (75 MHz, CDCl 3 ):  = 179. 1, 138.8, 138.6, 137.7, 133.3, 132.8, 131.4, 131.3, 129.5, 129.1, 127.2, 121.8, 119.5, 110.5, 94.0, 84.4, 21.6, 21.0.…”

“…1 H NMR (300 MHz, CDCl 3 ):  = 9.61 (d, J = 0.9 Hz, 1 H), 8.51 (d, J = 2.5 Hz, 1 H), 8.29 (dd, J = 8.7, 2.6 Hz, 1 H), 7.55 (d, J = 8.7 Hz, 1 H), 7.39-7.31 (m, 5 H), 7.24 (dd, J = 4.0, 1.6 Hz, 1 H), 7.19 (ddd, J = 2.6, 1.6, 0.9 Hz, 1 H), 6.56 (dd, J = 4.0, 2.7 Hz, 1 H). 13 C NMR (75 MHz, CDCl 3 ):  = 178. 5, 147.2, 145.7, 133.0, 131.7, 131.3, 129.4, 128.5, 128.4, 127.6, 124.0, 123.4, 123.2, 121.6, 111.5, 96.3, 83.2, 77.2.…”

“…1 H NMR (300 MHz, CDCl 3 ):  = 8.29 (d, J = 8.5 Hz, 1 H), 7.84-7.70 (m, 4 H), 7.64 (dd, J = 5.1, 2.0 Hz, 3 H), 7.50 (dd, J = 8.6, 1.4 Hz, 1 H), 7.43-7.36 (m, 4 H), 7.25 (dd, J = 8.5, 1.3 Hz, 1 H), 6.88-6.80 (m, 2 H). 13 C NMR (75 MHz, CDCl 3 ):  = 146.9, 145. 6, 144.8, 139.0, 134.2, 130.0, 129.74, 129.67, 129.5, 128.8, 128.5, 128.2, 127.0, 126.7, 125.5, 123.1, 121.3, 118.2, 115.7, 115.1, 113.3…”

“…43-7.35 (m, 3 H), 7.26-7.19 (m, 2 H), 6.87-6.79 (m, 2 H), 2.43 (d, J = 1.0 Hz, 3 H). 13 C NMR (75 MHz, CDCl 3 ):  = 144.9, 131.4, 131.3, 130.8, 130.7, 129.9, 129.4, 129.1, 128.9, 128.31, 128.28, 127.3, 126.9, 125.8, 124.7, 123.1, 120.1, 116.7, 94.7, 21.6…”

“…65-7.60 (m, 2 H), 7.60-7.54 (m, 3 H), 7.45 (d, J = 7.8 Hz, 2 H), 7.15 (d, J = 8.4 Hz, 1 H), 7.05 (s, 1 H), 6.76 (q, J = 2.9 Hz, 1 H), 6.57 (s, 1 H), 2.53 (d, J = 1.9 Hz, 3 H), 1.95 (d, J = 2.0 Hz, 3 H), 1.89 (d, J = 2.0 Hz, 3 H). 13 C NMR (75 MHz, CDCl 3 ):  = 148. 6, 145.7, 144.0, 142.1, 139.7, 136.1, 132.6, 132.1, 131.8, 130.8, 130.4, 129.7, 129.1, 129.0, 128.5, 126.8, 123.9, 121.6, 117.8, 115.0, 114.7, 112.9, 108.2, 77.2, 25.0, 21.4, 21.1. HRMS (ESI): m/z [M + H] calcd for C 28 H 23 N 2 : 387.1861; found: 387.1861.…”