Synthesis of Novel Pyridocarbazoles Analogues of Ellipticine

Abstract

Derivatives of pyrido[3,2-b]carbazole and pyrido[2,3-c]carbazole have been synthesized by the Vilsmeier–Haack reaction of N-(carbazol-3-yl)acetamides.

Key words

pyrido[3,2-b]carbazoles - pyrido[2,3-c]carbazoles - N-(carbazol-3-yl)acetamides - Vilsmeier–Haack reagent

• References and Notes

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• 17 General Procedure To a solution N-(6-ethoxy-9-ethyl-9H-carbazol-3-yl)acetamide (1 mmol) in POCl₃ (10 mmol) at 0–5 °C with stirring dry DMF (2.5 mmol) was added dropwise, and the mixture was heated at 70 °C for 12 h. On completion of the reaction (TLC), the mixture was poured onto crushed ice, the mixture stirred for 15 min, and the resulting solid filtered, washed well with H₂O and dried. The crude material was purified by column chromatography to separate the linear and angular products. 2-Chloro-9-ethoxy-6-ethyl-6H-pyrido[3,2-b]carbazole-3-carbaldehyde (2a) Mp 178–180. IR (KBR): 2921, 2844, 1683, 1576, 1471, 1286, 1169, 1084, 923 cm^–1. ¹H NMR (500 MHz, TMS, CDCl₃): δ = 10.49 (1 H, s), 8.78 (1 H, s), 8.59 (1 H, s), 7.65–7.63 (2 H, m), 7.27 (1 H, d, J = 10.0 Hz), 7.21 (1 H, d, J = 2.0 Hz), 4.32 (2 H, q, J = 7.5 Hz), 4.12 (2 H, q, J = 7.0 Hz), 1.44 (3 H, t, J = 7.0 Hz), 1.40 (3 H, t, J = 10.0 Hz). ¹³C NMR (125 MHz, TMS, CDCl₃): δ = 189.6, 153.4, 146.2, 143.0, 140.6, 139.6, 138.2, 131.2, 124.9, 124.8, 122.3, 118.9, 118.8, 109.4, 106.3, 104.8, 64.6, 38.1, 15.0, 13.4. GC–MS: m/z = 352.5. Anal. Calcd for C₂₀H₁₇ClN₂O₂: C, 68.09; H, 4.86; N, 7.94. Found: C, 68.23; H, 5.05; N, 7.85. 3-Chloro-10-ethoxy-7-ethyl-7H-pyrido[2,3-c]carbazole-2-carbaldehyde (3a) Mp 190–192. IR (KBR): 2935, 2850, 1673, 1585, 1460, 1283, 1175, 1087, 929 cm^–1. ¹H NMR (500 MHz, TMS, CDCl₃): δ = 10.55 (1 H, s), 9.33 (1 H, s), 7.94 (1 H, d, J = 9.5 Hz), 7.87 (1 H, d, J = 9.5 Hz), 7.83 (1 H, d, J = 2.0 Hz), 7.41 (1 H, d, J = 9.0 Hz), 7.16–7.14 (1 H, m), 4.42 (2 H, q, J = 7.5 Hz), 4.18 (2 H, q, J = 7.0 Hz), 1.48 (3 H, t, J = 7.0 Hz), 1.42 (3 H, t, J = 7.0 Hz). ¹³C NMR (125 MHz, TMS, CDCl₃): δ = 189.7, 154.2, 146.4, 146.3, 137.5, 134.6, 134.0, 126.1, 125.8, 123.2, 123.0, 118.0, 115.9, 115.0, 110.5, 105.8, 64.7, 38.0, 15.1, 14.6. GC–MS: m/z = 352.5. Anal. Calcd for C₂₀H₁₇ClN₂O₂: C, 68.09; H, 4.86; N, 7.94. Found: C, 67.79; H, 4.78; N, 8.16.
• 18 CCDC number of 2d is 1001381. Formula: C₁₈H₁₃Cl₁N₂O₁, unit cell parameters: a = 12.360(3), b = 13.961(3), c = 8.999(2), α = 90°, β = 108.336(3)°, γ = 90°, space group P21/c.