Microwave-assisted Synthesis of 5-Deaza-5,8-dihydropterins

Abstract

Three-component cyclocondensation of 2,6-diaminopyrimidin-4-one, 1,3-dicarbonyl compounds or benzoylacetonitrile and aromatic or aliphatic aldehydes in the presence or absence of zinc(II) bromide proceeds under microwave-assisted conditions to give 5-deaza-5,8-dihydropterins in good yield and with total control of regiochemistry.

Key words

dihydropyridopyrimidines - three-component cyclocondensations - microwave synthesis - heterocycles - Lewis acids

References

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13

In a typical experimental procedure, a mixture of 1,3-diaminopyrimidin-4-one 1 (0.20 g, 1.6 mmol), benzaldehyde (0.34 g, 3.2 mmol), ethyl acetoacetate (0.41 g, 3.2 mmol) and zinc(II) bromide (0.072 g, 0.32 mmol) in DMSO (7 mL) was irradiated for 20 min in a self-tunable CEM microwave synthesizer at 160 °C (initial power 30 W) and then allowed to cool. Water (25 mL) was added and the solution was left to stand for 5-6 h. The precipitated solid was filtered and washed with ethyl acetate to give 5-deaza-5-dihydropterin (3a) (0.38 g, 80%) as a pale yellow solid, mp 179-180 °C (Found: MH⁺, 327.1454. C₁₇H₁₈N₄O₃ requires MH, 327.1457); IR (KBr)/cm^-1: 3317, 3206, 2936, 1660, 1599, 1515, 1455, 1367, 1285, 1224, 1106, 1024; ¹H NMR (DMSO-d ₆; 400 MHz) δ (ppm) 10.34 (1 H, 3, 3-H), 9.06 (1 H, s, 8-H), 7.24-7.00 (5 H, m, PhH), 6.27 (2 H, s, NH₂), 4.82 (1 H, s, 5-H), 3.94 (2 H, q, J = 7.0 Hz, CH₂), 2.31 (3 H, s,
7-Me), 1.10 (3 H, t, J = 7.0 Hz, Me); ¹³C NMR (DMSO-d ₆; 100 MHz) δ (ppm) 167.2 (C), 161.8 (C), 154.4 (C), 154.3 (C), 148.5 (C), 147.5 (C), 128.0 (CH), 127.6 (CH), 125.9 (CH), 101.5 (C), 91.4 (C), 59.2 (CH), 36.8 (CH₂), 18.8 (Me), 14.5 (Me); m/z (APcI) 327 (MH⁺, 100%), 79 (67).